The Scientific World Journal: Pharmaceutics The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Preliminary Phytochemical Screening, Quantitative Analysis of Alkaloids, and Antioxidant Activity of Crude Plant Extracts from Ephedra intermedia Indigenous to Balochistan Mon, 13 Mar 2017 08:29:27 +0000 The aim of this study was to evaluate the antioxidant activity, screening the phytogenic chemical compounds, and to assess the alkaloids present in the E. intermedia to prove its uses in Pakistani folk medicines for the treatment of asthma and bronchitis. Antioxidant activity was analyzed by using 2,2-diphenyl-1-picryl-hydrazyl-hydrate assay. Standard methods were used for the identification of cardiac glycosides, phenolic compounds, flavonoids, anthraquinones, and alkaloids. High performance liquid chromatography (HPLC) was used for quantitative purpose of ephedrine alkaloids in E. intermedia. The quantitative separation was confirmed on Shimadzu 10AVP column (Shampack) of internal diameter (id) 3.0 mm and 50 mm in length. The extract of the solute in flow rate of 1 ml/min at the wavelength 210 nm and methanolic extract showed the antioxidant activity and powerful oxygen free radicals scavenging activities and the IC50 for the E. intermedia plant was near to the reference standard ascorbic acid. The HPLC method was useful for the quantitative purpose of ephedrine (E) and pseudoephedrine (PE) used for 45 samples of one species collected from central habitat in three districts (Ziarat, Shairani, and Kalat) of Balochistan. Results showed that average alkaloid substance in E. intermedia was as follows: PE (0.209%, 0.238%, and 0.22%) and E (0.0538%, 0.0666%, and 0.0514%). Rahman Gul, Syed Umer Jan, Syed Faridullah, Samiullah Sherani, and Nusrat Jahan Copyright © 2017 Rahman Gul et al. All rights reserved. Chemical Composition and In Vitro Antioxidant, Cytotoxic, Antimicrobial, and Larvicidal Activities of the Essential Oil of Mentha piperita L. (Lamiaceae) Sun, 01 Jan 2017 11:11:15 +0000 The essential oil was obtained by hydrodistillation and the identification and quantification of components were achieved with the use of GC-MS analysis. The antioxidant activity was evaluated by the method of sequestration of DPPH. Essential oils were used for study the cytotoxic front larvae of Artemia salina. In the evaluation of the antimicrobial activity of essential oils, we employed the disk-diffusion method. The potential larvicide in mosquito larvae of the third stage of development of Aedes aegypti to different concentrations of essential oils was evaluated. The major compounds found in the essential oils of M. piperita were linalool (51.8%) and epoxyocimene (19.3%). The percentage of antioxidant activity was %. The essential oil showed LC50 = 414.6 μg/mL front of A. saline and is considered highly toxic. It shows sensitivity and halos significant inhibition against E. coli. The essential possessed partial larvicidal efficiency against A. aegypti. Ryan da Silva Ramos, Alex Bruno Lobato Rodrigues, Ana Luzia Ferreira Farias, Ranggel Carvalho Simões, Mayara Tânia Pinheiro, Ricardo Marcelo dos Anjos Ferreira, Ledayane Mayana Costa Barbosa, Raimundo Nonato Picanço Souto, João Batista Fernandes, Lourivaldo da Silva Santos, and Sheylla Susan Moreira da Silva de Almeida Copyright © 2017 Ryan da Silva Ramos et al. All rights reserved. Optimized Extraction of Resveratrol from Arachis repens Handro by Ultrasound and Microwave: A Correlation Study with the Antioxidant Properties and Phenol Contents Tue, 27 Dec 2016 15:39:44 +0000 The vegetal species Arachis repens, commonly known as peanut grass, was studied and, for the first time, we detected the presence of the bioactive compound trans-resveratrol (-RSV). We compared the efficiency of three different methodologies (conventional maceration [CM], ultrasound-assisted extractions [UAE], and microwave-assisted extractions [MAE]) concerning total phenolics (TP) and resveratrol (-RSV) content, followed by antioxidant activity (AA) evaluation. By CM, at 1 h, the highest RSV content ( mg/L) and, correspondingly, the highest DPPH capture (%) were found. The TP contents, at 1 h, presented the highest value ( mg/g GAE). By the UAE, the maximum yields of TP (357.18 mg/g GAE) and RSV (2.14 mg/L), as well as, the highest AA (70.95%), were obtained by 5 min after a maceration pretreatment, on the solid-solvent ratio 1 : 40 w/v. For MAE, a central composite rotatable design (CCRD) was applied followed by the FFD design in order to evaluate the statistical effects of four independent variables on the extraction of RSV. The optimal conditions established for obtaining the highest recovery (2.516 mg/g) were 20 min; 90% MeOH aq.; 120 rpm; 60°C; and solid-solvent ratio: 1 : 35 w/v. Relevant correlations were established considering the TP and RSV contents, as well as the AA, corroborating obvious advantages of such techniques in terms of high extraction efficiency in shorter times. Leonardo Garcia, Renata Garcia, Georgia Pacheco, Felipe Sutili, Rodrigo De Souza, Elisabeth Mansur, and Ivana Leal Copyright © 2016 Leonardo Garcia et al. All rights reserved. Development and Evaluation of Stability of a Gel Formulation Containing the Monoterpene Borneol Mon, 09 May 2016 11:33:36 +0000 Borneol is a bicyclic monoterpenoid alcohol commonly used in traditional Chinese and Indian medicine. It is extracted from the essential oil of various medicinal plants. It has antibacterial, analgesic, and anti-inflammatory action proven in studies that used oral and intraperitoneal applications of this monoterpene in mice. The current study was designed to develop a topical gel formulation containing the monoterpene borneol using carbopol as gel base and to evaluate its stability. The prepared formulation was subjected to physical characterization and physical-chemistry assessment. The gel was prepared from carbopol and 5% of borneol. The prepared gel was subjected to pharmacotechnical tests such as its pH, viscosity, conductivity, spreadability, centrifugation, and accelerated stability with freezing-thaw cycle. The borneol was successfully incorporated into the carbopol formulation. Borneol gel (BG5) showed good stability after eight months of its development and after 12 days in the freeze-thaw cycle, not showing statistical difference in pH value, conductivity, and viscosity before and after test. Furthermore, the formulation showed a good spreadability. Therefore, it was concluded that the formulation could be very promising alternative for the topical or transdermal treatment of skin diseases. Milla Gabriela Belarmino Dantas, Silvio Alan Gonçalves Bomfim Reis, Camila Mahara Dias Damasceno, Larissa Araújo Rolim, Pedro José Rolim-Neto, Ferdinando Oliveira Carvalho, Lucindo José Quintans-Junior, and Jackson Roberto Guedes da Silva Almeida Copyright © 2016 Milla Gabriela Belarmino Dantas et al. All rights reserved. The Use of D-Optimal Mixture Design in Optimizing Development of Okara Tablet Formulation as a Dietary Supplement Thu, 11 Jun 2015 07:40:09 +0000 The usage of soy is increasing year by year. It increases the problem of financial crisis due to the limited sources of soybeans. Therefore, production of oral tablets containing the nutritious leftover of soymilk production, called okara, as the main ingredient was investigated. The okara tablets were produced using the direct compression method. The percentage of okara, guar gum, microcrystalline cellulose (Avicel PH-101), and maltodextrin influenced tablets’ hardness and friability which are analyzed using a D-optimal mixture design. Composition of Avicel PH-101 had positive effects for both hardness and friability tests of the tablets. Maltodextrin and okara composition had a significant positive effect on tablets’ hardness, but not on percentage of friability of tablets. However, guar gum had a negative effect on both physical tests. The optimum tablet formulation was obtained: 47.0% of okara, 2.0% of guar gum, 35.0% of Avicel PH-101, and 14.0% of maltodextrin. Nur Izzati Mohamad Zen, Siti Salwa Abd Gani, Rosnah Shamsudin, and Hamid Reza Fard Masoumi Copyright © 2015 Nur Izzati Mohamad Zen et al. All rights reserved. An Improved LC-MS/MS Method for Simultaneous Determination of the Eleven Bioactive Constituents for Quality Control of Radix Angelicae Pubescentis and Its Related Preparations Wed, 20 May 2015 10:07:11 +0000 An improved LC-MS/MS method was developed for simultaneous determination of eleven bioactive constituents of Radix Angelicae Pubescentis and its related preparations. It was the first report on the quantification of bioactive constituents in different preparations of Radix Angelicae Pubescentis by LC-MS/MS analytical method. These samples were separated with an Agilent Zorbax Extend reversed-phase C18 column (1.8 μm, 4.6 × 100 mm) by linear gradient elution using aqueous ammonium acetate and acetonitrile as mobile phase. The flow rate was 0.3 mL min−1. The eleven bioactive constituents showed good regression within test ranges and the recoveries were in the range of 87.1–110%. The limit of detections and quantifications for most of the major constituents were less than 0.5 and 1.0 ng mL−1, respectively. All results indicated that the developed method could be readily utilized as a suitable quality control method for Radix Angelicae Pubescentis and related preparations. Jin Li, Qiu-Hong Zhang, Jun He, Er-wei Liu, Xiu-mei Gao, and Yan-xu Chang Copyright © 2015 Jin Li et al. All rights reserved. Development and Evaluation of Nanoemulsifying Preconcentrate of Curcumin for Colon Delivery Wed, 11 Mar 2015 07:25:48 +0000 The present study aimed to develop and optimize a nanoemulsifying preconcentrate formulation of curcumin with good emulsification ability and optimal globule size, for controlled targeting in colon. Content of formulation variables, namely, (Peceol), (Cremophor-EL), and (Transcutol HP), were optimized by Box-Behnken design of experiments for its impact on mean globule size (), emulsification time (), and time required for drug release (85%) in phosphate buffer (pH 7.2), (). Transmission electron micrographs confirmed that there is no coalescence among globules, with size range concordant with the globule size analysis by dynamic light scattering technique (100 nm). 3D plots indicated that concentration of formulation ingredients significantly influences the formulation properties (globule size, emulsification time, and drug release). In vitro release profile (in phosphate buffer; pH 7.2) represents the fact that more than 50% of the drug was released within initial 15 min whereas in vivo release showed limited systemic absorption ( 200 ng/mL) of curcumin. Stability study ensures the protection of drug in alkaline media which may further confirm the localised delivery of drug to colonic region. Study demonstrated that the nanoemulsifying preconcentrate can be a promising system for the colon specific delivery of curcumin to treat local pathologies. Jyoti Wadhwa, Abhay Asthana, Gyati Shilakari, Arun Kumar Chopra, and Ranjit Singh Copyright © 2015 Jyoti Wadhwa et al. All rights reserved. Formulation and Evaluation of Galantamine Gel as Drug Reservoir in Transdermal Patch Delivery System Thu, 26 Feb 2015 06:51:54 +0000 Galantamine hydrobromide is formulated in tablets and capsules prescribed through oral delivery for the treatment of Alzheimer’s disease. However, oral delivery of drugs can cause severe side effects such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide could avoid these unwanted side effects. In this work, galantamine hydrobromide was formulated in gel drug reservoir which was then fabricated in the transdermal patch. The in vitro drug release studies revealed that the drug release from the donor chamber to receptor chamber of Franz diffusion cell was affected by the amount of polymer, amount of neutralizer, amount of drug, types of permeation enhancer, and amount of permeation enhancer. Visual observations of the gels showed that all formulated gels are translucent, homogeneous, smooth, and stable. These gels have pH in the suitable range for skin. The gel also showed high drug content uniformity. Hence, this formulation can be further used in the preparation of transdermal patch drug delivery system. Woo Fong Yen, Mahiran Basri, Mansor Ahmad, and Maznah Ismail Copyright © 2015 Woo Fong Yen et al. All rights reserved. Effect of In Vitro Transcorneal Approach of Aceclofenac Eye Drops through Excised Goat, Sheep, and Buffalo Corneas Tue, 13 Jan 2015 11:39:10 +0000 The current study involves the evaluation of factors that influence the transcorneal permeation of aqueous drops of aceclofenac ophthalmic formulation through freshly excised goat, sheep, and buffalo corneas. Aceclofenac formulation with different concentrations 0.1–0.5% (w/v) and with different pH and different preservatives, was taken into account. The amount of drug permeated from different formulations was estimated using an Franz diffusion cell. A linear increase in drug permeation was observed with increase in pH (5.5 to 7.4). The apparent permeability coefficient was found to be maximum on goat cornea and maximum transport of aceclofenac was observed at physiological pH of tears (i.e., 7). The results advocate that aceclofenac 0.5% (w/v) ophthalmic solution (pH 7.0) containing BAK (0.01%) provides maximum in vitro ocular permeability through goat, sheep, and buffalo corneas. Vivek Dave, Sarvesh Paliwal, Sachdev Yadav, and Swapnil Sharma Copyright © 2015 Vivek Dave et al. All rights reserved. Application of Vibrational Spectroscopy Supported by Theoretical Calculations in Identification of Amorphous and Crystalline Forms of Cefuroxime Axetil Sun, 11 Jan 2015 14:01:09 +0000 FT-IR and Raman scattering spectra of cefuroxime axetil were proposed for identification studies of its crystalline and amorphous forms. An analysis of experimental spectra was supported by quantum-chemical calculations performed with the use of B3LYP functional and 6-31G(d,p) as a basis set. The geometric structure of a cefuroxime axetil molecule, HOMO and LUMO orbitals, and molecular electrostatic potential were also determined by using DFT (density functional theory). The benefits of applying FT-IR and Raman scattering spectroscopy for characterization of drug subjected to degradation were discussed. Alicja Talaczyńska, Kornelia Lewandowska, Anna Jelińska, Piotr Garbacki, Agnieszka Podborska, Przemysław Zalewski, Irena Oszczapowicz, Adam Sikora, Maciej Kozak, and Judyta Cielecka-Piontek Copyright © 2015 Alicja Talaczyńska et al. All rights reserved. Development, Characterization, and Pharmacodynamic Evaluation of Hydrochlorothiazide Loaded Self-Nanoemulsifying Drug Delivery Systems Tue, 16 Dec 2014 06:52:59 +0000 The objective of the current work was to develop optimized self-nanoemulsifying drug delivery systems (SNEDDS) and evaluate their in vitro and in vivo performance. The research comprised various studies which includes solubility studies in various vehicles, pseudoternary phase diagram construction, and preparation and characterization of SNEDDS along with in vitro dissolution and in vivo pharmacodynamic profiling. Based on dissolution profile, a remarkable increase in rate of dissolution was observed in comparison with plain drug and marketed formulation. Optimized SNEDDS formulation was composed of Capmul MCM (19.17% w/w), Tween 80 (57.5% w/w), Transcutol P (12.7% w/w), and HCT (4.17% w/w). In vivo pharmacodynamic evaluation in Wistar rats showed considerable increase in pharmacological effect of HCT by SNEDDS formulation as compared with plain HCT. Pankajkumar S. Yadav, Ekta Yadav, Amita Verma, and Saima Amin Copyright © 2014 Pankajkumar S. Yadav et al. All rights reserved. Nanospray Drying as a Novel Technique for the Manufacturing of Inhalable NSAID Powders Tue, 16 Dec 2014 00:10:44 +0000 The aim of this research was to evaluate the potential of the nanospray drier as a novel apparatus for the manufacturing of a dry powder for inhalation containing ketoprofen lysinate, a nonsteroidal anti-inflammatory drug able to control the inflammation in cystic fibrosis patients. We produced several ketoprofen lysinate and leucine powder batches by means of nanospray dryer, studying the influence of process parameters on yield, particle properties (size distribution and morphology), and, mainly, aerodynamic properties of powders. Micronized particles were prepared from different hydroalcoholic solutions (alcohol content from 0 to 30% v/v) using ketoprofen in its lysine salt form and leucine as dispersibility enhancer in different ratios (from 5 to 15% w/w) with a total solid concentration ranging from 1 to 7% w/v. Results indicated that the spray head equipped with a 7 µm nozzle produced powders too big to be inhaled. The reduction of nozzle size from 7 to 4 µm led to smaller particles suitable for inhalation but, at the same time, caused a dramatic increase in process time. The selection of process variables, together with the nozzle pretreatment with a surfactant solution, allowed us to obtain a free flowing powder with satisfying aerosol performance, confirming the usefulness of the nanospray drier in the production of powder for inhalation. Aquino Rita Patrizia, Stigliani Mariateresa, Del Gaudio Pasquale, Mencherini Teresa, Sansone Francesca, and Russo Paola Copyright © 2014 Aquino Rita Patrizia et al. All rights reserved. Gastroretentive Pulsatile Release Tablets of Lercanidipine HCl: Development, Statistical Optimization, and In Vitro and In Vivo Evaluation Wed, 26 Nov 2014 00:10:18 +0000 The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs) of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO) WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for various in vitro physicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were tested in vivo in New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20% w/w) with coat weight 480 mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release both in vitro and in vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure. Gagganapalli Santhoshi Reddy, Usha Yogendra Nayak, Praful Balavant Deshpande, and Srinivas Mutalik Copyright © 2014 Gagganapalli Santhoshi Reddy et al. All rights reserved. Development and Optimization of Polymeric Self-Emulsifying Nanocapsules for Localized Drug Delivery: Design of Experiment Approach Mon, 24 Nov 2014 09:57:52 +0000 The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, (oil), (polymeric emulsifier), and (adsorbent), was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size () and encapsulation efficiency () of the formulation. Polymeric nanocapsules with an average diameter of 100–180 nm and an encapsulation efficiency of 64.85 ± 0.12% were obtained. In vitro studies revealed that formulations released the drug after 5 h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile ( 200 ng/mL) that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0–2 h in upper GIT; 2–4 h in small intestine; and 4–24 h in the lower intestine). Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32 μM) in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon. Jyoti Wadhwa, Abhay Asthana, Sumeet Gupta, Gyati Shilkari Asthana, and Ranjit Singh Copyright © 2014 Jyoti Wadhwa et al. All rights reserved. Antinociceptive and Anti-Inflammatory Activities of Bridelia retusa Methanolic Fruit Extract in Experimental Animals Mon, 17 Nov 2014 09:31:04 +0000 Antinociceptive and anti-inflammatory potentials of methanolic extract of Bridelia retusa fruit (BRME) were evaluated against different animal models in rodents. Antinociceptive effects of BRME were assessed in mice using the acetic acid-induced writhing and formalin test. Anti-inflammatory effects of BRME in three different doses, namely, 100, 200, and 400 mg/kg, were evaluated by utilizing different animal models representing various changes associated with inflammation, namely, carrageenan-induced paw oedema, histamine and serotonin-induced paw oedema, arachidonic acid-induced paw oedema, formalin-induced paw oedema, TPA-induced ear oedema, acetic acid-induced vascular permeability, total WBC count in paw fluid, and myeloperoxidase assay. Also BRME was phytochemically evaluated using chromatographic method. The BRME did not exhibit any signs of toxicity up to a dose of 2000 mg/kg. The extract showed statistical significant inhibition of induced nociception and inflammation in dose dependent manner. The higher dose of extract significantly inhibited pain and inflammation against control (). HPLC results revealed the presence of gallic acid and ellagic acid as phytoconstituents in BRME and it was proven as anti-inflammatory agents. The present study scientifically demonstrated the antinociceptive and anti-inflammatory potential of fruit of B. retusa methanolic extract. These effects may be attributed to the presence of polyphenolic phytoconstituents in the extract. Tekeshwar Kumar and Vishal Jain Copyright © 2014 Tekeshwar Kumar and Vishal Jain. All rights reserved. Significance of Algal Polymer in Designing Amphotericin B Nanoparticles Wed, 12 Nov 2014 09:12:36 +0000 Development of oral amphotericin B (AmB) loaded nanoparticles (NPs) demands a novel technique which reduces its toxicity and other associated problems. Packing of AmB in between two oppositely charged ions by polyelectrolyte complexation technique proved to be a successful strategy. We have developed a novel carrier system in form of polyelectrolyte complex of AmB by using chitosan (CS) and porphyran (POR) as two oppositely charged polymers with TPP as a crosslinking agent. Initially POR was isolated from Porphyra vietnamensis followed by the fact that its alkali induced safe reduction in molecular weight was achieved. Formulation was optimized using three-factor three-level (33) central composite design. High concentration of POR in NPs was confirmed by sulfated polysaccharide (SP) assay. Degradation and dissolution studies suggested the stability of NPs over wide pH range. Hemolytic toxicity data suggested the safety of prepared formulation. In vivo and in vitro antifungal activity demonstrated the high antifungal potential of optimized formulation when compared with standard drug and marketed formulations. Throughout the study TPP addition did not cause any significant changes. Therefore, these experimental oral NPs may represent an interesting carrier system for the delivery of AmB. Saurabh Bhatia, Vikash Kumar, Kiran Sharma, Kalpana Nagpal, and Tanmoy Bera Copyright © 2014 Saurabh Bhatia et al. All rights reserved. Preparation and Characterization of Novel PBAE/PLGA Polymer Blend Microparticles for DNA Vaccine Delivery Mon, 27 Oct 2014 00:00:00 +0000 Context. Poly(beta-amino ester) (PBAE) with its pH sensitiveness and Poly(lactic-co-glycolic acid) (PLGA) with huge DNA cargo capacity in combination prove to be highly efficient as DNA delivery system. Objective. To study the effectiveness of novel synthesized PBAE polymer with PLGA blend at different ratios in DNA vaccine delivery. Methods. In the present study, multifunctional polymer blend microparticles using a combination of PLGA and novel PBAE polymers A1 (bis(3-(propionyloxy)propyl)3,3′-(propane-1,3-diyl-bis(methylazanediyl))dipropanoate) and A2 (bis(4-(propionyloxy)butyl)3,3′-(ethane-1,2-diyl-bis(isopropylazanediyl))dipropanoate) at different ratios (85 : 15, 75 : 25, and 50 : 50) were prepared by double emulsion solvent removal method. The microparticles were characterized for cytotoxicity, transfection efficiency, and DNA encapsulation efficiency. Result. It was evident from results that among the microparticles prepared with PLGA/PBAE blend the PLGA : PBAE at 85 : 15 ratio was found to be more effective combination than the microparticles prepared with PLGA alone in terms of transfection efficiency and better DNA integrity. Microparticles made of PLGA and PBAE A1 at 85 : 15 ratio, respectively, were found to be less toxic when compared with microparticles prepared with A2 polymer. Conclusion. The results encourage the use of the synthesized PBAE polymer in combination with PLGA as an effective gene delivery system. Meenashi Vanathi Balashanmugam, Sivagurunathan Nagarethinam, Hitesh Jagani, Venkata Rao Josyula, Abdulmohsen Alrohaimi, and Nayanabhirama Udupa Copyright © 2014 Meenashi Vanathi Balashanmugam et al. All rights reserved. Development and Characterization of Novel Site Specific Hollow Floating Microspheres Bearing 5-Fu for Stomach Targeting Tue, 14 Oct 2014 11:29:30 +0000 Multiple-unit-type oral floating hollow microspheres of 5-fluorouracil (5-Fu) were developed using modified solvent evaporation technique to prolong gastric residence time, to target stomach cancer, and to increase drug bioavailability. The prepared microspheres were characterized for micromeritic properties, floating behavior, entrapment efficiency, and scanning electron microscopy (SEM). The in vitro drug release and floating behavior were studied in simulated gastric fluid (SGF) at pH 1.2. The yield of microspheres was obtained up to %. Microspheres showed passable flow properties. Based on optical microscopy, particle size was found to be ranging from to  m. SEM confirmed spherical size, perforated smooth surface, and a hollow cavity inside the microspheres. Different kinetic models for drug release were also applied on selected batches. Peeyush Bhardwaj, Deepti Chaurasia, Ranjit Singh, and Anoop Swarup Copyright © 2014 Peeyush Bhardwaj et al. All rights reserved. Antitumor Activity of Monoterpenes Found in Essential Oils Tue, 14 Oct 2014 11:19:32 +0000 Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action for bioactive substances are presented. Marianna Vieira Sobral, Aline Lira Xavier, Tamires Cardoso Lima, and Damião Pergentino de Sousa Copyright © 2014 Marianna Vieira Sobral et al. All rights reserved. In Vivo Hypoglycaemic Effect and Inhibitory Mechanism of the Branch Bark Extract of the Mulberry on STZ-Induced Diabetic Mice Wed, 06 Aug 2014 12:43:50 +0000 Branch bark extract (BBE) derived from the mulberry cultivar Husang 32 (Morus multicaulis L.) with aqueous alcohol solution has been investigated as an inhibitor of α-glycosidase in vitro. Mulberry BBE was orally administered to STZ-induced diabetic mice for three weeks, and it improved the weight gain and ameliorated the swelling of liver and kidney in diabetic mice. Obviously, mulberry BBE not only can reduce the abnormally elevated levels of serum insulin and ameliorate insulin resistance induced by STZ, but also it regulates dyslipidemia in diabetic mice. To understand this therapeutic effect and the regulatory mechanisms of BBE in diabetic mice, a qRT-PCR experiment was performed, indicating that the mulberry BBE can regulate the mRNA expression of glycometabolism genes in diabetic mice, including glucose-6-phosphatase (G6Pase), glucokinase (GCK), and phosphoenolpyruvate carboxykinase (PEPCK), thereby regulating sugar metabolism and reducing the blood glucose level in diabetic mice. The mulberry BBE can increase the mRNA expression of the genes Ins1, Ins2 and pancreatic duodenal homeobox-1 (PDX-1) and may decrease the insulin resistance in diabetic mice. Those results provide an important basis for making the best use of mulberry branch resources and producing biomedical drugs with added value. Hua-Yu Liu, Meng Fang, and Yu-Qing Zhang Copyright © 2014 Hua-Yu Liu et al. All rights reserved. Inducing Effect of Dihydroartemisinic Acid in the Biosynthesis of Artemisinins with Cultured Cells of Artemisia annua by Enhancing the Expression of Genes Thu, 17 Jul 2014 10:48:16 +0000 Artemisinin has been used in the production of “artemisinin combination therapies” for the treatment of malaria. Feeding of precursors has been proven to be one of the most effective methods to enhance artemisinin production in plant cultured cells. At the current paper, the biosynthesis of artemisinin (ART) and its four analogs from dihydroartemisinic acid (DHAA) in suspension-cultured cells of Artemisia annua were investigated. ARTs were detected by HPLC/GC-MS and isolated by various chromatography methods. The structures of four DHAA metabolites, namely, dihydro-epi-deoxyarteannuin B, arteannuin I, arteannuin K, and 3-β-hydroxy-dihydro-epi-deoxyarteannuin B, were elucidated by physicochemical and spectroscopic analyses. The correlation between gene expression and ART content was investigated. The results of RT-PCR showed that DHAA could up-regulate expression of amorpha-4,11-diene synthase gene (ADS), amorpha-4,11-diene C-12 oxidase gene (CYP71AV1), and farnesyl diphosphate synthase gene (FPS) (3.19-, 7.21-, and 2.04-fold higher than those of control group, resp.), which indicated that biosynthesis processes from DHAA to ART were enzyme-mediated. Jianhua Zhu, Jiazeng Yang, Zihan Zeng, Wenjin Zhang, Liyan Song, Wei Wen, and Rongmin Yu Copyright © 2014 Jianhua Zhu et al. All rights reserved. Cytotoxic Constituents from the Rhizomes of Curcuma zedoaria Sun, 13 Jul 2014 00:00:00 +0000 Curcuma zedoaria also known as Temu putih is traditionally used in food preparations and treatment of various ailments including cancer. The cytotoxic activity of hexane, dichloromethane, ethyl acetate, methanol, and the methanol-soxhlet extracts of Curcuma zedoaria rhizomes was tested on two human cancer cell lines (Ca Ski and MCF-7) and a noncancer cell line (HUVEC) using MTT assay. Investigation on the chemical components in the hexane and dichloromethane fractions gave 19 compounds, namely, labda-8(17),12 diene-15,16 dial (1), dehydrocurdione (2), curcumenone (3), comosone II (4), curcumenol (5), procurcumenol (6), germacrone (7), zerumbone epoxide (8), zederone (9), 9-isopropylidene-2,6-dimethyl-11-oxatricyclo[,5]undec-6-en-8-ol (10), furanodiene (11), germacrone-4,5-epoxide (12), calcaratarin A (13), isoprocurcumenol (14), germacrone-1,10-epoxide (15), zerumin A (16), curcumanolide A (17), curcuzedoalide (18), and gweicurculactone (19). Compounds (1–19) were evaluated for their antiproliferative effect using MTT assay against four cancer cell lines (Ca Ski, MCF-7, PC-3, and HT-29). Curcumenone (3) and curcumenol (5) displayed strong antiproliferative activity ( and  μg/mL, resp.) and were found to induce apoptotic cell death on MCF-7 cells using phase contrast and Hoechst 33342/PI double-staining assay. Thus, the present study provides basis for the ethnomedical application of Curcuma zedoaria in the treatment of breast cancer. Omer Abdalla Ahmed Hamdi, Syarifah Nur Syed Abdul Rahman, Khalijah Awang, Norhanom Abdul Wahab, Chung Yeng Looi, Noel Francis Thomas, and Sri Nurestri Abd Malek Copyright © 2014 Omer Abdalla Ahmed Hamdi et al. All rights reserved. Traditional Uses, Chemical Constituents, and Biological Activities of Bixa orellana L.: A Review Mon, 23 Jun 2014 11:40:16 +0000 Bixa orellana L., popularly known as “urucum,” has been used by indigenous communities in Brazil and other tropical countries for several biological applications, which indicates its potential use as an active ingredient in pharmaceutical products. The aim of this work was to report the main evidence found in the literature, concerning the ethnopharmacology, the biological activity, and the phytochemistry studies related to Bixa orellana L. Therefore, this work comprises a systematic review about the use of Bixa orellana in the American continent and analysis of the data collected. This study shows the well-characterized pharmacological actions that may be considered relevant for the future development of an innovative therapeutic agent. Daniela de Araújo Vilar, Marina Suênia de Araujo Vilar, Túlio Flávio Accioly de Lima e Moura, Fernanda Nervo Raffin, Márcia Rosa de Oliveira, Camilo Flamarion de Oliveira Franco, Petrônio Filgueiras de Athayde-Filho, Margareth de Fátima Formiga Melo Diniz, and José Maria Barbosa-Filho Copyright © 2014 Daniela de Araújo Vilar et al. All rights reserved. Evaluation of Skin Permeation and Analgesic Activity Effects of Carbopol Lornoxicam Topical Gels Containing Penetration Enhancer Thu, 19 Jun 2014 12:14:49 +0000 The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD), beta-cyclodextrin (β-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31 μg/cm2/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation. Saleh A. Al-Suwayeh, Ehab I. Taha, Fahad M. Al-Qahtani, Mahrous O. Ahmed, and Mohamed M. Badran Copyright © 2014 Saleh A. Al-Suwayeh et al. All rights reserved. Stability of Ceftiofur Sodium and Cefquinome Sulphate in Intravenous Solutions Tue, 03 Jun 2014 12:05:53 +0000 Stability of ceftiofur sodium and cefquinome sulphate in intravenous solutions was studied. Chromatographic separation and quantitative determination were performed by using a high-performance liquid chromatography with UV-DAD detection. During the stability study, poly(vinylchloride) minibags were filled with a solution containing 5 mg of ceftiofur sodium or cefquinome sulphate and diluted to 0.2 mg/mL with suitable intravenous solution depending on the test conditions. The solutions for the study were protected from light and stored at room temperature (22°C), refrigerated (6°C), frozen (−20°C) for 30 days, and then thawed at room temperature. A comparison of results obtained at 22°C and 6°C for the same intravenous solutions showed that temperature as well as components of solutions and their concentration had an influence on the stability of ceftiofur sodium and cefquinome sulphate. It was found that ceftiofur sodium and cefquinome sulphate dissolved in intravenous solutions used in this study may be stored at room temperature and at 6°C for up to 48 h. Agnieszka Dołhań, Anna Jelińska, and Marcelina Bębenek Copyright © 2014 Agnieszka Dołhań et al. All rights reserved. Preparation and Evaluation of Novel In Situ Gels Containing Acyclovir for the Treatment of Oral Herpes Simplex Virus Infections Mon, 24 Mar 2014 07:00:13 +0000 The objective of this work was to develop an oral mucosal drug delivery system to facilitate the local and systemic delivery of acyclovir for the treatment of oral herpes infection caused by the herpes simplex virus (HSV). An in situ gelling system was used to increase the residence time and thus the bioavailability of acyclovir in oral mucosa. Temperature and pH trigged in situ gel formulations were prepared by cold method using polymers like poloxamer 407, carbopol 934, and HPMC. Glycerin and a mixture of tween 80 and ethanol (1 : 2 ratio) were used as the drug dissolving solvent. The pH of carbopol containing formulation was adjusted to pH 5.8 while the pH of poloxamer solution was adjusted to pH 7. These formulations were evaluated for sol-gel transition temperature, gelling capacity, pH, viscosity, spreadability, gel strength, drug content, ex-vitro permeation, and mucoadhesion. The gelation temperatures of all the formulations were within the range of 28–38°C. All the formulations exhibited fairly uniform drug content (98.15–99.75%). Drug release study of all the formulations showed sustained release properties. The release of drug through these in situ gel formulations followed the Higuchi model and Korsmeyer peppas model mechanism. Binu Chaudhary and Surajpal Verma Copyright © 2014 Binu Chaudhary and Surajpal Verma. All rights reserved. Ophthalmic Drug Dosage Forms: Characterisation and Research Methods Tue, 18 Mar 2014 11:35:47 +0000 This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient’s compliance. Przemysław Baranowski, Bożena Karolewicz, Maciej Gajda, and Janusz Pluta Copyright © 2014 Przemysław Baranowski et al. All rights reserved. Sialometry of Upper Labial Minor Glands: A Clinical Approach by the Use of Weighing Method Schirmer’s Test Strips Paper Sun, 09 Mar 2014 09:12:15 +0000 Objectives. To establish referential values ranges of hyposalivation and normosalivation for the salivary flow rate (SFR) of upper labial (LS) and palatal (PS) mucosa using Schirmer's test strips paper and as a second goal to determine the values ranges of the SFR of palatal (PS) and upper labial (LS) mucosa in subjects with and without xerostomia. Methods. A cross-sectional study was conducted among subjects distributed in three groups according to their unstimulated and stimulated whole saliva. Results. 144 subjects were enrolled in groups as follows: severe hyposalivation (), mild hyposalivation (), and normosalivation (). The mean and the 95% confidence interval for the LS flow rate (μL/cm2/min) were 3.2 (2.46 to 3.94), 5.86 (4.96 to 6.75), and 9.08 (7.63 to 10.53) () for each group, respectively. The PS results were 1.01 (0.68 to 1.34), 1.72 (1.31 to 2.13), and 2.44 (1.66 to 3.22) (). Xerostomia complainers presented lower rates of LS (5.17 (4.06 to 6.23)) than non-complainers (7.33 (6.4 to 8.27)) (). Conclusions. The test was reliable to provide referential values ranges for LS flow rate measurement and was shown to be valid to distinguish normosalivation from severe and mild hyposalivation and also to predict xerostomia. Denise Pinheiro Falcão, Soraya Coelho Leal, Celi Novaes Vieira, Andy Wolff, Tayana Filgueira Galdino Almeida, Fernanda de Paula e Silva Nunes, Rivadávio Fernandes Batista de Amorim, and Ana Cristina Bezerra Copyright © 2014 Denise Pinheiro Falcão et al. All rights reserved. Histological Ex Vivo Evaluation of Peri-Incisional Thermal Effect Created by a New-Generation CO2 Superpulsed Laser Tue, 25 Feb 2014 13:00:19 +0000 The purpose of this study is the evaluation of the histological effects of a new-generation superpulsed CO2 laser through an “ex vivo” study. A CO2 (λ = 10,600 nm) ultra-speed laser (SmartUS20D, DEKA, Florence, Italy) has been used at different parameters from 2 to 4 watt in Continuous Wave (CW) and Pulsed Wave (PW, 50 Hz) to obtain 30 samples from pig cadaver tongues. All the specimens have been subdivided into 6 groups (from A to F) and each group consisted of 5 samples. A final specimen has been taken by scalpel and used as control group. Histological analysis has been performed using an optical microscope (Leica DM 2000) at a magnification of ×40. Results showed that histological readability was optimal in all the samples. The thermal damage has been negligible in all the groups. Furthermore, the average of thermal damage was 0,095 mm in the epithelial, while it was 0.245 mm in the connective tissue. Statistical analysis using Graphpad Prism 5 software showed no significant differences among the groups. CO2 laser demonstrated a good surgical effectiveness provoking little peripheral damage onto the cut edges and allowing a safe histological diagnosis. G. Palaia, A. Del Vecchio, A. Impellizzeri, G. Tenore, P. Visca, F. Libotte, C. Russo, and U. Romeo Copyright © 2014 G. Palaia et al. All rights reserved. Formulation Optimization of Arecoline Patches Sun, 23 Feb 2014 13:36:53 +0000 The response surface methodology (RSM) including polynomial equations has been used to design an optimal patch formulation with appropriate adhesion and flux. The patch formulations were composed of different polymers, including Eudragit RS 100 (ERS), Eudragit RL 100 (ERL) and polyvinylpyrrolidone K30 (PVP), plasticizers (PEG 400), and drug. In addition, using terpenes as enhancers could increase the flux of the drug. Menthol showed the highest enhancement effect on the flux of arecoline. Pao-Chu Wu, Pi-Ju Tsai, Shin-Chen Lin, and Yaw-Bin Huang Copyright © 2014 Pao-Chu Wu et al. All rights reserved. Problem-Based Learning in Pharmaceutical Education: A Systematic Review and Meta-Analysis Wed, 19 Feb 2014 10:51:08 +0000 Objective. To assess the effects of problem-based learning (PBL) on the learning achievements of pharmacy students. Methods. We searched for controlled studies that compared PBL to traditional learning in pharmacy courses (graduate and undergraduate) in the major literature databases up to January 2014. Two independent researchers selected the studies, extracted the data, and assessed the quality of the studies. Meta-analyses of the outcomes were performed using a random effects model. Results. From 1,988 retrieved records, five were included in present review. The studies assessed students’ impressions about the PBL method and compared student grades on the midterm and final examinations. PBL students performed better on midterm examinations (odds ratio ; confidence interval [IC] 95%: 1.16, 1.89) and final examinations (; IC 95%: 1.06, 2.43) compared with students in the traditional learning groups. No difference was found between the groups in the subjective evaluations. Conclusion. pharmacy students’ knowledge was improved by the PBL method. Pharmaceutical education courses should consider implementing PBL. Tais F. Galvao, Marcus T. Silva, Celiane S. Neiva, Laura M. Ribeiro, and Mauricio G. Pereira Copyright © 2014 Tais F. Galvao et al. All rights reserved. Formulation and Evaluation of Guggul Lipid Nanovesicles for Transdermal Delivery of Aceclofenac Thu, 06 Feb 2014 11:18:10 +0000 Context. Most new drugs have low water solubility and liposome is an important formulation to administer such drugs; however, it is quite unstable and has negligible systemic absorption. Objective. Aceclofenac nanovesicles were made using guggul lipid for formulating stable transdermal formulation. Materials and Methods. Guggul lipid was formulated into vesicles along with cholesterol and dicetyl phosphate using film hydration method. The formulations were analyzed for physicochemical properties and stability. Then its skin permeation and anti-inflammatory activity were determined. Results. Both categories of vesicles (PC and GL) showed optimum physicochemical properties; however, accelerated stability study showed considerable differences. GL-1 was appreciably stable for over 6 months at 4°C. Corresponding gels (PCG-1 and GLG-1) showed Cmax values at 4.98 and 7.32 μg/mL along with the Tmax values at 4 and 8 hours, respectively. GLG-1 inhibited edema production by 90.81% in 6 hours. Discussion. PC liposomes are unstable at higher temperature and upon longer storage. The formulation with higher lipid content (GL-1) showed good drug retention after 24 hours and appreciable stability both at higher temperature and for longer duration. Guggul lipid being a planar molecule might be stacked in vesicle wall with cholesterol. Conclusion. The composition of the nanovesicle played an important role in stability and drug permeation. Guggul lipid is suitable for producing stable vesicles. Praveen Kumar Gaur, Shikha Mishra, and Vidhu Aeri Copyright © 2014 Praveen Kumar Gaur et al. All rights reserved. The Influence of pH and Temperature on the Stability of N-[(Piperidine)methylene]daunorubicin Hydrochloride and a Comparison of the Stability of Daunorubicin and Its Four New Amidine Derivatives in Aqueous Solutions Thu, 06 Feb 2014 07:34:47 +0000 The influence of pH and temperature on the stability of N-[(piperidine)methylene]daunorubicin hydrochloride (PPD) was investigated. Degradation was studied using an HPLC method. Specific acid-base catalysis of PPD involves hydrolysis of protonated molecules of PPD catalyzed by hydrogen ions and spontaneous hydrolysis under the influence of water zwitterions, unprotonated molecules, and monoanions of PPD. The thermodynamic parameters of these reactions, energy, enthalpy, and entropy, were calculated. Also, the stability of daunorubicin and its new amidine derivatives (piperidine, morpholine, pyrrolidine, and hexahydroazepin-1-yl) in aqueous solutions was compared and discussed. Mikołaj Piekarski, Agnieszka Dołhań, Judyta Cielecka-Piontek, Przemysław Zalewski, Witold Kycler, Aleksandra Kaczmarek, Artur Firlej, Irena Oszczapowicz, and Anna Jelińska Copyright © 2014 Mikołaj Piekarski et al. All rights reserved. Formulation and Characterization of Drug Loaded Nonionic Surfactant Vesicles (Niosomes) for Oral Bioavailability Enhancement Sun, 02 Feb 2014 08:07:38 +0000 Nonionic surfactant vesicles (niosomes) were formulated with an aim of enhancing the oral bioavailability of tenofovir disoproxil fumarate (TDF), an anti-HIV drug. Niosomes were formulated by conventional thin film hydration technique with different molar ratios of surfactant, cholesterol, and dicetyl phosphate. The formulated niosomes were found spherical in shape, ranging from 2.95 μm to 10.91 μm in size. Vesicles with 1 : 1 : 0.1 ratios of surfactant : cholesterol : dicetyl phosphate with each grade of span were found to have higher entrapment efficiencies, which were further selected for in vitro and in vivo studies. Vesicles formulated with sorbitan monostearate were found to have maximum drug release (99.091%) at the end of 24 hours and followed zero order release kinetics. The results of in vivo study revealed that the niosomes significantly enhanced the oral bioavailability of TDF in rats after a dose of 95 mg/kg. The average relative bioavailability of niosomes in relation to plane drug solution was found to be 2.58, indicating more than twofold increase in oral bioavailability of TDF. Significant increase in mean residential time (MRT) was also found, reflecting release retarding efficacy of the vesicles. In conclusion, niosomes could be a promising delivery for TDF with improved oral bioavailability and prolonged release profiles. Sunil Kamboj, Vipin Saini, and Suman Bala Copyright © 2014 Sunil Kamboj et al. All rights reserved. Optimization (Central Composite Design) and Validation of HPLC Method for Investigation of Emtricitabine Loaded Poly(lactic-co-glycolic acid) Nanoparticles: In Vitro Drug Release and In Vivo Pharmacokinetic Studies Thu, 30 Jan 2014 15:27:09 +0000 The objective of the current study is to develop nanoparticles (NPs) drug delivery system of emtricitabine solely using poly(lactic-co-glycolic acid) (PLGA) and evaluate its in vitro and in vivo release performance by systematically optimized HPLC method using Formulation by Design (FbD). NPs were evaluated for in vitro release and in vivo absorption study. The desired chromatographic separation was achieved on a Phenomenex C18 (250 mm × 4.6 mm I.D., 5 μm) column, under isocratic conditions using UV detection at 280 nm. The optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen phosphate buffer (pH 6.8), methanol, and 2% acetonitrile in a ratio of (83 : 15 : 2, v/v/v) at a flow rate of 1 mL/min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.040–2.0 μg/mL, with retention time of 4.39 min. An average encapsulation efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order release and about 95% drug being released within 15 days in PBS (pH 7.4). In conclusion, the proposed optimized method was successfully applied for the determination of in vitro and in vivo release studies of emtricitabine NPs. Gurinder Singh and Roopa S. Pai Copyright © 2014 Gurinder Singh and Roopa S. Pai. All rights reserved. Development and Optimization of Osmotically Controlled Asymmetric Membrane Capsules for Delivery of Solid Dispersion of Lycopene Wed, 29 Jan 2014 12:42:02 +0000 The aim of the present investigation is to develop and statistically optimize the osmotically controlled asymmetric membrane capsules of solid dispersion of lycopene. Solid dispersions of lycopene with -cyclodextrin in different ratios were prepared using solvent evaporation method. Solubility studies showed that the solid dispersion with 1 : 5 (lycopene : -cyclodextrin) exhibited optimum solubility (56.25 mg/mL) for osmotic controlled delivery. Asymmetric membrane capsules (AMCs) were prepared on glass mold pins via dip coating method. Membrane characterization by scanning electron microscopy showed inner porous region and outer dense region. Central composite design response surface methodology was applied for the optimization of AMCs. The independent variables were ethyl cellulose (), glycerol (), and NaCl () which were varied at different levels to analyze the effect on dependent variables (percentage of cumulative drug release () and correlation coefficient of drug release ()). The effect of independent variables on the response was significantly influential. The F18 was selected as optimized formulation based on percentage of CDR (cumulative drug release) of 85.63% and correlation coefficient of 0.9994. The optimized formulation was subjected to analyze the effect of osmotic pressure and agitational intensity on percentage of CDR. The drug release was independent of agitational intensity but was dependent on osmotic pressure of dissolution medium. Nitin Jain, Rashmi Sareen, Neeraj Mahindroo, and K. L. Dhar Copyright © 2014 Nitin Jain et al. All rights reserved. Synthesis, Characterization, and Evaluation of a Novel Amphiphilic Polymer RGD-PEG-Chol for Target Drug Delivery System Tue, 21 Jan 2014 10:43:00 +0000 An amphiphilic polymer RGD-PEG-Chol which can be produced in large scale at a very low cost has been synthesized successfully. The synthesized intermediates and final products were characterized and confirmed by 1H nuclear magnetic resonance spectrum (1H NMR) and Fourier transform infrared spectrum (FT-IR). The paclitaxel- (PTX-) loaded liposomes based on RGD-PEG-Chol were then prepared by film formation method. The liposomes had a size within 100 nm and significantly enhanced the cytotoxicity of paclitaxel to B16F10 cell as demonstrated by MTT test (IC50 = 0.079 μg/mL of RGD-modified PTX-loaded liposomes compared to 9.57 μg/mL of free PTX). Flow cytometry analysis revealed that the cellular uptake of coumarin encapsulated in the RGD-PEG-Chol modified liposome was increased for HUVEC cells. This work provides a reasonable, facile, and economic approach to prepare peptide-modified liposome materials with controllable performances and the obtained linear RGD-modified PTX-loaded liposomes might be attractive as a drug delivery system. Shi Zeng, Fengbo Wu, Bo Li, Xiangrong Song, Yu Zheng, Gu He, Cheng Peng, and Wei Huang Copyright © 2014 Shi Zeng et al. All rights reserved. Development of a Controlled Release of Salicylic Acid Loaded Stearic Acid-Oleic Acid Nanoparticles in Cream for Topical Delivery Tue, 21 Jan 2014 07:31:48 +0000 Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release. J. O. Woo, M. Misran, P. F. Lee, and L. P. Tan Copyright © 2014 J. O. Woo et al. All rights reserved. PCL/PHBV Microparticles as Innovative Carriers for Oral Controlled Release of Manidipine Dihydrochloride Thu, 16 Jan 2014 09:32:24 +0000 Microparticles of poly(ε-caprolactone) (PCL) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) containing manidipine dihydrochloride (MAN) were successfully prepared by the simple emulsion/solvent evaporation method. All formulations showed loading efficiency rates greater than 80% and average particle size less than 8 μm. Formulations had spherical shape with smooth and porous surface for PCL and PHBV, respectively. According to Fourier-transform infrared spectroscopy, initial components were not chemically modified during microencapsulation. X-ray diffraction patterns and differential scanning calorimetry demonstrated that this process led to drug amorphization. In vitro dissolution studies showed that all microparticles prolonged MAN release, mainly which one obtained using PCL that contained 5% of drug loaded (PCL-M5). Animal studies demonstrated that formulation PCL-M5 was able to keep the variation of mean arterial pressure after phenylephrine administration up to 24 hours. These data confirmed the sustained antihypertensive effect of the investigated microparticles. Results provided an experimental basis for using formulation PCL-M5 as a feasible carrier for oral controlled release of MAN intended for treating high blood pressure. Fernanda Malaquias Barboza, Willian Moreira Machado, Luiz Renato Olchanheski Junior, Josiane Padilha de Paula, Sônia Faria Zawadzki, Daniel Fernandes, and Paulo Vitor Farago Copyright © 2014 Fernanda Malaquias Barboza et al. All rights reserved. Design, Synthesis, and In Vitro Kinetics Study of Atenolol Prodrugs for the Use in Aqueous Formulations Sun, 12 Jan 2014 16:48:47 +0000 Based on DFT, MP2, and the density functional from Truhlar group (hybrid GGA: MPW1k) calculations for an acid-catalyzed hydrolysis of nine Kirby’s N-alkylmaleamic acids and two atenolol prodrugs were designed. The calculations demonstrated that the amide bond cleavage is due to intramolecular nucleophilic catalysis by the adjacent carboxylic acid group and the rate-limiting step is determined based on the nature of the amine leaving group. In addition, a linear correlation of the calculated and experimental rate values has drawn credible basis for designing atenolol prodrugs that are bitterless, are stable in neutral aqueous solutions, and have the potential to release the parent drug in a sustained release manner. For example, based on the calculated B3LYP/6-31 G (d,p) rates, the predicted (a time needed for 50% of the prodrug to be converted into drug) values for atenolol prodrugs ProD 1-ProD 2 at pH 2 were 65.3 hours (6.3 hours as calculated by GGA: MPW1K) and 11.8 minutes, respectively. In vitro kinetic study of atenolol prodrug ProD 1 demonstrated that the was largely affected by the pH of the medium. The determined values in 1N HCl, buffer pH 2, and buffer pH 5 were 2.53, 3.82, and 133 hours, respectively. Rafik Karaman, Alaa Qtait, Khulod Khayyat Dajani, and Saleh Abu Lafi Copyright © 2014 Rafik Karaman et al. All rights reserved. Validation of a Thin-Layer Chromatography for the Determination of Hydrocortisone Acetate and Lidocaine in a Pharmaceutical Preparation Mon, 06 Jan 2014 11:31:35 +0000 A new specific, precise, accurate, and robust TLC-densitometry has been developed for the simultaneous determination of hydrocortisone acetate and lidocaine hydrochloride in combined pharmaceutical formulation. The chromatographic analysis was carried out using a mobile phase consisting of chloroform + acetone + ammonia (25%) in volume composition 8 : 2 : 0.1 and silica gel 60F254 plates. Densitometric detection was performed in UV at wavelengths 200 nm and 250 nm, respectively, for lidocaine hydrochloride and hydrocortisone acetate. The validation of the proposed method was performed in terms of specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, and robustness. The applied TLC procedure is linear in hydrocortisone acetate concentration range of  μg·spot−1, and from  μg·spot−1 for lidocaine hydrochloride. The developed method was found to be accurate (the value of the coefficient of variation CV [%] is less than 3%), precise (CV [%] is less than 2%), specific, and robust. LOQ of hydrocortisone acetate is 0.198 μg·spot−1 and LOD is 0.066 μg·spot−1. LOQ and LOD values for lidocaine hydrochloride are 0.270 and 0.090 μg·spot−1, respectively. The assay value of both bioactive substances is consistent with the limits recommended by Pharmacopoeia. Małgorzata Dołowy, Katarzyna Kulpińska-Kucia, and Alina Pyka Copyright © 2014 Małgorzata Dołowy et al. All rights reserved. Bilayered Films Based on Novel Polymer Derivative for Improved Ocular Therapy of Gatifloxacin Thu, 02 Jan 2014 09:06:14 +0000 Context. Thiomers could prove to be suitable mucoadhesives for fabrication of ocular inserts. Objective. The study intends to explore the application of thiolated sodium alginate (TSA) to the preparation of bilayered ocular inserts of gatifloxacin. Methods. Cysteine moieties were grafted onto sodium alginate (SA) and the resultant thiomer was characterized for relevant physicochemical properties. Bilayered inserts were fabricated with a mucoadhesive immediate release layer composed of either SA or TSA and a sustained release layer composed of acrylates. Films were prepared by solvent evaporation and evaluated for mechanical properties, drug content, and in vitro release. Results and Discussion. The synthesized TSA possessed  μmol thiol groups/gm and its solutions thickened on standing due to disulphide bridging. Its films showed improved mucoadhesion and also a strikingly beneficial property of resisting erosion and remaining as a hydrated adhesive layer for the duration of drug release. The bilayered films were found to be flexible, with good folding endurance, uniform thickness, and appropriate drug content, and showed a release of about 80% of loaded gatifloxacin in 12 h. Conclusion. The study demonstrates promise in employing thiolated polymer in conjunction with acrylates for the design of ocular inserts for twice a day therapy with gatifloxacin. Naval Dinesh Aher and Hema Ajit Nair Copyright © 2014 Naval Dinesh Aher and Hema Ajit Nair. All rights reserved. Analysis of Size Correlations for Microdroplets Produced by Ultrasonic Atomization Tue, 31 Dec 2013 14:35:26 +0000 Microencapsulation techniques are widely applied in the field of pharmaceutical production to control drugs release in time and in physiological environments. Ultrasonic-assisted atomization is a new technique to produce microencapsulated systems by a mechanical approach. Interest in this technique is due to the advantages evidenceable (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) when comparing it to more conventional techniques. In this paper, the groundwork of atomization is introduced, the role of relevant parameters in ultrasonic atomization mechanism is discussed, and correlations to predict droplets size starting from process parameters and material properties are presented and tested. Annalisa Dalmoro, Anna Angela Barba, and Matteo d’Amore Copyright © 2013 Annalisa Dalmoro et al. All rights reserved. Antioxidant Characterization of Oak Extracts Combining Spectrophotometric Assays and Chemometrics Wed, 25 Dec 2013 15:58:25 +0000 Antioxidant characteristics of leaves, twigs, and acorns from two Serbian oak species Quercus robur L. and Quercus petraea L. from Vojvodina province (northern Serbia) were investigated. 80% ethanol (in water) extracts were used for antiradical power (ARP) determinations against , , and radicals, ferric reducing antioxidant power (FRAP), total phenol, tannin, flavonoid, and proanthocyanidin contents. Permanganate reducing antioxidant capacity (PRAC) was determined using water extracts. Beside, mentioned parameters, soluble proteins, lipid peroxidation (LP), pigments and proline contents were also determined. The data of different procedures were compared and analyzed by multivariate techniques (correlation matrix calculation and principal component analysis (PCA)). PCA found that investigated organs of two different oak tree species possess similar antioxidant characteristics. The superior antioxidant characteristics showed oak leaves over twigs and acorns and seem to be promising source of antioxidants with possible use in industry and pharmacy. Boris M. Popović, Dubravka Štajner, Ružica Ždero, Saša Orlović, and Zoran Galić Copyright © 2013 Boris M. Popović et al. All rights reserved. Pharmaceutical Point of View on Parenteral Nutrition Sun, 22 Dec 2013 11:51:20 +0000 Parenteral nutrition—a form of administering nutrients, electrolytes, trace elements, vitamins, and water—is a widely used mode of therapy applied in many diseases, in patients of different ages both at home and in hospital. The success of nutritional therapy depends chiefly on proper determination of the patient’s energetic and electrolytic needs as well as preparation and administration of a safe nutritional mixture. As a parenterally administered drug, it is expected to be microbiologically and physicochemically stable, with all of the components compatible with each other. It is very difficult to obtain a stable nutritional mixture due to the fact that it is a complex, two-phase drug. Also, the risk of incompatibility between mixture components and packaging should be taken into consideration and possibly eliminated. Since parenteral nutrition is a part of therapy, simultaneous use of drugs may cause pharmacokinetic and pharmacodynamic interactions as well as those with the pharmaceutical phase. The aim of this paper is to discuss such aspects of parenteral nutrition as mixture stability, methodology, and methods for determining the stability of nutritional mixtures and drugs added to them. M. Stawny, R. Olijarczyk, E. Jaroszkiewicz, and A. Jelińska Copyright © 2013 M. Stawny et al. All rights reserved. Heteropterys cotinifolia: A Neuropharmacological and Phytochemical Approach with Possible Taxonomic Implications Thu, 19 Dec 2013 16:05:29 +0000 Heteropterys cotinifolia (Malpighiaceae) has been used in traditional Mexican medicine mainly for the treatment of nervous disorders. However, the specific neuropharmacological activities responsible for this use remain to be defined. The present study evaluates the antidepressant and anxiolytic effects produced by the methanolic extract of Heteropterys cotinifolia and the influence of such effects on motor activity in ICR mice. Our results show that the methanolic extract of Heteropterys cotinifolia produces a dose-dependent antidepressant effect in the forced swimming test in mice at doses from 31 to 310 mg/kg, with no reduction of mice locomotion. However, no anxiolytic properties were observed. Our findings suggest that the main extract compounds identified as chlorogenic acid and rutin may be involved in the antidepressant effects. To our knowledge, the present study constitutes the first report of pharmacological and phytochemical data of Heteropterys cotinifolia. The presence of flavonoids in the methanolic extract of Heteropterys cotinifolia may also provide further data to characterize taxonomically this species in order to be distinguished from others species closely related and belonging to the same genus. Maira Huerta-Reyes, Alejandro Zamilpa, Rafael Álvarez-Chimal, José Ángel Luna-Manzanares, María Esther León-Velasco, Arturo Aguilar-Rojas, Manuel Jiménez-Estrada, and María Guadalupe Campos-Lara Copyright © 2013 Maira Huerta-Reyes et al. All rights reserved. In Vitro Permeation of Micronized and Nanonized Alaptide from Semisolid Formulations Wed, 18 Dec 2013 16:36:00 +0000 This study is focused on in vitro permeation of the original Czech compound, a skin/mucosa tissue regeneration promoter, known under the international nonproprietary name “alaptide,” in micronized and nanonized forms. Alaptide showed a great potential for local applications for treatment and/or regeneration of the injured skin. The above mentioned technological modifications influence the permeation of alaptide through artificial or biological membranes, such as PAMPA or skin. The permeation of micronized and nanonized form of alaptide formulated to various semisolid pharmaceutical compositions through full-thickness pig ear skin using a Franz cell has been investigated in detail. In general, it can be concluded that the nanonized alaptide permeated through the skin less than the micronized form; different observations were made for permeation through the PAMPA system, where the micronized form showed lower permeation than the nanonized alaptide. Radka Opatrilova, Aneta Cernikova, Lenka Coufalova, Jiri Dohnal, and Josef Jampilek Copyright © 2013 Radka Opatrilova et al. All rights reserved. Pharmacokinetic Delivery and Metabolizing Rate of Nicardipine Incorporated in Hydrophilic and Hydrophobic Cyclodextrins Using Two-Compartment Mathematical Model Tue, 03 Dec 2013 18:43:52 +0000 The dispersion routes of cyclodextrin complexes with nicardipine (NC), such as hydrophilic hydroxypropyl--cyclodextrin (NC/HPCD) and hydrophobic triacetyl--cyclodextrin (NC/TACD), through the body for controlled drug delivery and sustained release have been examined. The two-compartment pharmacokinetic model described the mechanisms of how the human body handles with ingestion of NC-cyclodextrin complexes in gastrointestinal tract (GI), distribution in plasma, and their metabolism in the liver. The model showed that drug bioavailability was significantly improved after oral administration of cyclodextrin complexes. The mathematical significance of this study to predict nicardipine delivery using pharmacokinetic two-compartment mathematical model with linear ordinary differential equations (ODE) approach represents a valuable tool to emphasize its effectiveness and metabolizing rate and diminish the side effects. Sergey Shityakov and Carola Förster Copyright © 2013 Sergey Shityakov and Carola Förster. All rights reserved. Glycyrrhetinic Acid-Poly(ethylene glycol)-glycyrrhetinic Acid Tri-Block Conjugates Based Self-Assembled Micelles for Hepatic Targeted Delivery of Poorly Water Soluble Drug Mon, 25 Nov 2013 10:25:29 +0000 The triblock 18β-glycyrrhetinic acid-poly(ethylene glycol)-18β-glycyrrhetinic acid conjugates (GA-PEG-GA) based self-assembled micelles were synthesized and characterized by FTIR, NMR, transmission electron microscopy, and particle size analysis. The GA-PEG-GA conjugates having the critical micelle concentration of  M were used to form nanosized micelles, with mean diameters of 159.21 ± 2.2 nm, and then paclitaxel (PTX) was incorporated into GA-PEG-GA micelles by self-assembly method. The physicochemical properties of the PTX loaded GA-PEG-GA micelles were evaluated including in vitro cellular uptake, cytotoxicity, drug release profile, and in vivo tissue distribution. The results demonstrate that the GA-PEG-GA micelles had low cytotoxicity and good ability of selectively delivering drug to hepatic cells in vitro and in vivo by the targeting moiety glycyrrhetinic acid. In conclusion, the GA-PEG-GA conjugates have potential medical applications for targeted delivery of poor soluble drug delivery. Fengbo Wu, Ting Xu, Chi Liu, Can Chen, Xiangrong Song, Yu Zheng, and Gu He Copyright © 2013 Fengbo Wu et al. All rights reserved. Thiol Modification of Psyllium Husk Mucilage and Evaluation of Its Mucoadhesive Applications Wed, 20 Nov 2013 13:59:40 +0000 Thiol functionalization of psyllium was carried out to enhance its mucoadhesive potential. Thiolation of psyllium was achieved by esterification with thioglycolic acid. Thiolation was observed to change the surface morphology of psyllium from fibrous to granular and result in a slight increase in the crystallinity and swelling. Thiolated psyllium was found to contain 3.282 m moles of thiol groups/g of the polymer. Mucoadhesive applications of thiolated psylium were explored by formulating gels using metronidazole as the model drug. On comparative evaluation thiolated psyllium gels showed 3-fold higher mucoadhesive strength than the psyllium gels as determined by modified physical balance using chicken buccal pouch. The results of in vitro release study revealed that thiolated psyllium gels provided a prolonged release of metronidazole. Further, the psyllium and thiolated psyllium gels were found to release the drug following first-order kinetics by combination of polymer relaxation and diffusion through the matrix. Meenakshi Bhatia and Munish Ahuja Copyright © 2013 Meenakshi Bhatia and Munish Ahuja. All rights reserved. Radiation Sterilization of Anthracycline Antibiotics in Solid State Sun, 03 Nov 2013 08:26:17 +0000 The impact of ionizing radiation generated by a beam of electrons of 25–400 kGy on the stability of such analogs of anthracycline antibiotics as daunorubicin (DAU), doxorubicin (DOX), and epidoxorubicin (EPI) was studied. Based on EPR results, it was established that unstable free radicals decay exponentially with the half-time of 4 days in DAU and DOX and 7 days in EPI after irradiation. Radiation-induced structural changes were analyzed with the use of spectrophotometric methods (UV-Vis and IR) and electron microscope imaging (SEM). A chromatographic method (HPLC-DAD) was applied to assess changes in the contents of the analogs in the presence of their impurities. The study showed that the structures of the analogs did not demonstrate any significant alterations at the end of the period necessary for the elimination of unstable free radicals. The separation of main substances and related substances (impurities and potential degradation products) allowed determining that no statistically significant changes in the content of particular active substances occurred and that their conversion due to the presence of free radicals resulting from exposure to an irradiation of 25 kGy (prescribed to ensure sterility) was not observed. A. Kaczmarek, J. Cielecka-Piontek, P. Garbacki, K. Lewandowska, W. Bednarski, B. Barszcz, P. Zalewski, W. Kycler, I. Oszczapowicz, and A. Jelińska Copyright © 2013 A. Kaczmarek et al. All rights reserved. Synthesis and Biological Evaluation of 2-Hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(Alkoxycarbonyl)amino]benzoates Tue, 29 Oct 2013 10:33:29 +0000 A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport. Jan Tengler, Iva Kapustíková, Matúš Peško, Rodney Govender, Stanislava Keltošová, Petr Mokrý, Peter Kollár, Jim O'Mahony, Aidan Coffey, Katarína Král'ová, and Josef Jampílek Copyright © 2013 Jan Tengler et al. All rights reserved. Resveratrol-Loaded Polymeric Nanoparticles: Validation of an HPLC-PDA Method to Determine the Drug Entrapment and Evaluation of Its Antioxidant Activity Thu, 24 Oct 2013 13:52:09 +0000 Poly(lactic acid) (PLA) and PLA-poly(ethylene glycol) (PLA-PEG) nanoparticles containing resveratrol (RVT) were developed, and their antioxidant activity was evaluated. An analytical method using high performance liquid chromatography (HPLC)/photodiode array (PDA) detection was also developed and validated for RVT determination in nanoparticles. The mobile phase consisted of methanol : water (51 : 49, v/v) flowed at 0.9 mL/min, and the PDA detector was set at wavelength of 306 nm. The mean diameter of the nanoparticles varied between 180 and 220 nm, and the encapsulation efficiency of RVT ranged from 60% to 88%. The nanoparticles containing RVT were evaluated for their ability to scavenge the radical (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) (ABTS•+). The profile obtained from the PLA nanoparticles containing RVT demonstrated that after 24 h, there was almost no increase in antioxidant activity, which was lower than that of the free RVT and RVT-loaded PLA-PEG nanoparticles. For PLA-PEG nanoparticles, the radical-scavenging activity of RVT was shown to increase with time, and after 48 h, it was similar to that observed with free RVT. Gabriela da Rocha Lindner, Najeh Maissar Khalil, and Rubiana Mara Mainardes Copyright © 2013 Gabriela da Rocha Lindner et al. All rights reserved. Chemically Cross-Linked Poly(acrylic-co-vinylsulfonic) Acid Hydrogel for the Delivery of Isosorbide Mononitrate Wed, 23 Oct 2013 18:30:12 +0000 We report synthesis, characterization, and drug release attributes of a series of novel pH-sensitive poly(acrylic-co-vinylsulfonic) acid hydrogels. These hydrogels were prepared by employing free radical polymerization using ethylene glycol dimethacrylate (EGDMA) and benzyl peroxide (BPO) as cross-linker and initiator, respectively. Effect of acrylic acid (AA), polyvinylsulfonic acid (PVSA), and EGDMA on prepared hydrogels was investigated. All formulations showed higher swelling at high pHs and vice versa. Formulations containing higher content of AA and EGDMA show reduced swelling, but one with higher content of PVSA showed increased swelling. Hydrogel network was characterized by determining structural parameters and loaded with isosorbide mononitrate. FTIR confirmed absence of drug polymer interaction while DSC and TGA demonstrated molecular dispersion of drug in a thermally stable polymeric network. All the hydrogel formulations exhibited a pH dependent release of isosorbide mononitrate which was found to be directly proportional to pH of the medium and PVSA content and inversely proportional to the AA contents. Drug release data were fitted to various kinetics models. Results indicated that release of isosorbide mononitrate from poly(AA-co-VSA) hydrogels was non-Fickian and that the mechanism was diffusion-controlled. Talib Hussain, Mahvash Ansari, Nazar Muhammad Ranjha, Ikram Ullah Khan, and Yasser Shahzad Copyright © 2013 Talib Hussain et al. All rights reserved. Optimization and Evaluation of Desloratadine Oral Strip: An Innovation in Paediatric Medication Mon, 21 Oct 2013 11:41:35 +0000 Patients, especially children, are the most difficult to treat in all groups of population mainly because they can not swallow the solid dosage form. Due to this reason they are often prescribed liquid dosage forms. But these formulations have their own disadvantages (lack of dose accuracy during administration, spitting by children, spillage, lack of stability, difficulty in transportation, etc.). Oral strip technology is one such technology to surpass these disadvantages. Desloratadine, a descarboethoxy derivative of loratadine, is a second generation antihistaminic drug approved for usage in allergic rhinitis among paediatric population and is available in markets as suspension. An attempt has been made to design and optimize the oral strip containing desloratadine as an active ingredient. Oral strip was optimized with the help of optimal experimental design using polymer concentration, plasticizer type, and plasticizer concentration as independent variables. Prepared oral strips were evaluated for physicochemical parameter, mechanical strength parameters, disintegration time, dissolution, surface pH, and moisture sorption tendency. Optimized formulation was further evaluated by scanning electron microscopy, moisture content, and histological alteration in oral mucosa. Accelerated stability studies were also carried out for optimized formulations. Results were analysed with the help of various statistical tools at and . Harmanpreet Singh, Mandeep Kaur, and Hitesh Verma Copyright © 2013 Harmanpreet Singh et al. All rights reserved. Application of HPLC with ELSD Detection for the Assessment of Azelaic Acid Impurities in Liposomal Formulation Tue, 08 Oct 2013 13:50:43 +0000 In the course of research and development of a new pharmaceutical formulation of azelaic acid in the liposomal form, we developed a rapid and accurate method for the detection of impurities using high-performance liquid chromatography. A chromatographic column from Merck (Purospher Star RP C18, 250–4 mm (5 μm) was used in the assay, and the mobile phase gradient consisted of three phases: A—methanol : water (5 : 95) + 1.5% (v/v) acetic acid; B—water : methanol (5 : 95) + 1.5% (v/v) acetic acid; and C—chloroform. Detection of the impurities and the active substance was performed by an evaporative light-scattering detector. The method was validated for selectivity, system precision, method precision, limit of detection, and response rates. The proposed method can be used to detect impurities in the liposomal formulation of azelaic acid. The method enables separation of azelaic acid from the identified and unidentified impurities and from the excipients used in the drug form. Stanislaw Han, Katarzyna Karlowicz-Bodalska, Dorota Szura, Lukasz Ozimek, and Witold Musial Copyright © 2013 Stanislaw Han et al. All rights reserved. Assessment of Antioxidant and Cytotoxicity Activities of Saponin and Crude Extracts of Chlorophytum borivilianum Wed, 02 Oct 2013 17:34:25 +0000 The present paper focused on antioxidant and cytotoxicity assessment of crude and total saponin fraction of Chlorophytum borivilianum as an important medicinal plant. In this study, three different antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), ferrous ion chelating (FIC), and β-carotene bleaching (BCB) activity) of crude extract and total saponin fraction of C. borivilianum tubers were performed. Crude extract was found to possess higher free radical scavenging activity (ascorbic acid equivalents 2578 ± 111 mg AA/100 g) and bleaching activity (IC50 = 0.7 mg mL−1), while total saponin fraction displayed higher ferrous ion chelating (EC50 = 1 mg mL−1). Cytotoxicity evaluation of crude extract and total saponin fraction against MCF-7, PC3, and HCT-116 cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) cell viability assay indicated a higher cytotoxicity activity of the crude extract than the total saponin fraction on all cell lines, being most effective and selective on MCF-7 human breast cancer cell line. Mehdi Farshad Ashraf, Maheran Abd Aziz, Johnson Stanslas, Ismanizan Ismail, and Mihdzar Abdul Kadir Copyright © 2013 Mehdi Farshad Ashraf et al. All rights reserved. Design, Development, and Optimization of Polymeric Based-Colonic Drug Delivery System of Naproxen Tue, 01 Oct 2013 08:43:24 +0000 The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting. Pooja Sharma, Anuj Chawla, and Pravin Pawar Copyright © 2013 Pooja Sharma et al. All rights reserved. Synthesis and Properties of Macrocyclic Butanoic Acid Conjugates as a Promising Delivery Formulation for the Nutrition of Colon Wed, 18 Sep 2013 14:02:46 +0000 Butanoic acid plays a significant role in the maintenance of mucosal health and is the preferred energy substrate for the cells in the colon. Here, butanoic acid was selectively conjugated to the secondary hydroxyl group of β-cyclodextrin through ester bond using sodium hydride as the deprotonation reagent. The preliminary release behaviors of butanoic acid in rat gastrointestinal tract contents were investigated at 37°C within 12 h. In the contents of stomach, the conjugates did seldom release butanoic acid, released butanoic acid only 5.8% in the contents of small intestine, and released butanoic acid significantly up to 38.4% in the contents of colon. These results indicate that the conjugate activation took place site specifically in the rat colonic contents, via the biodegradation by glycosidases and hydrolases in the colon. Therefore, the β-cyclodextrin conjugates of butanoic acid may be of value as an orally administered colon-specific formulation for the nutrition of colon. Jingui Cheng, Benpeng Li, Peipei Ma, Mengying Liu, and Zhizhong Wang Copyright © 2013 Jingui Cheng et al. All rights reserved. Isotretinoin Oil-Based Capsule Formulation Optimization Mon, 26 Aug 2013 17:35:54 +0000 The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (), hydrogenated coconut oil (), and soybean oil (). The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM). Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (, , and ) showed more potential influence than that of the main factors (, , and ). An optimal predicted formulation with , , , and release values of 12.3%, 36.7%, 73.6%, and 92.7% at , , and of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile. Pi-Ju Tsai, Chi-Te Huang, Chen-Chou Lee, Chi-Lin Li, Yaw-Bin Huang, Yi-Hung Tsai, and Pao-Chu Wu Copyright © 2013 Pi-Ju Tsai et al. All rights reserved. Stability of a Cosmetic Multiple Emulsion Loaded with Green Tea Extract Sat, 24 Aug 2013 09:59:57 +0000 Multiple emulsions are excellent and exciting potential systems for the delivery of useful cosmetic agents. The work describes stability of a multiple emulsion for cosmetic purpose, loaded with extract of Camellia sinensis L. (Theaceae) in concentration of 5%. The formulation constitutes of cetyl dimethicone copolyol and polyoxyethylene (20) cetyl ether as emulsifiers and was characterised and monitored for various physicochemical aspects. Centrifugation has no devastating effect on physical destabilization/phase separation observed for 30 days. Mean globule sizes of multiple droplets were found in the range of 10.29 ± 4.4 μm to 12.77 ± 5.1 μm and of inner droplets were in the range of 0.8 ± 0.4 μm to 1.6 ± 0.8 μm. All samples exhibited shear thinning behavior with increase in shear stress. The results of the present study indicate that multiple emulsions can be used as carrier of 5% Camellia sinensis L. extract to enhance desired effects. The developed physically and chemically stable system is an effective system for targeting skin layers; however, long-term stability at elevated temperatures may be needed with suitable modifications, if required. Tariq Mahmood and Naveed Akhtar Copyright © 2013 Tariq Mahmood and Naveed Akhtar. All rights reserved. Antibiotic Susceptibility Profile of Aeromonas Species Isolated from Wastewater Treatment Plant Mon, 13 Aug 2012 08:51:12 +0000 This study assessed the prevalence of antibiotic-resistant Aeromonas species isolated from Alice and Fort Beaufort wastewater treatment plant in the Eastern Cape Province of South Africa. Antibiotic susceptibility was determined using the disc diffusion method, and polymerase chain reaction (PCR) assay was employed for the detection of antibiotics resistance genes. Variable susceptibilities were observed against ciprofloxacin, chloramphenicol, nalidixic acid, gentamicin, minocycline, among others. Aeromonas isolates from both locations were 100% resistant to penicillin, oxacillin, ampicillin, and vancomycin. Higher phenotypic resistance was observed in isolates from Fort Beaufort compared to isolates from Alice. Class A pse1 β-lactamase was detected in 20.8% of the isolates with a lower detection rate of 8.3% for blaTEM gene. Class 1 integron was present in 20.8% of Aeromonas isolates while class 2 integron and TetC gene were not detected in any isolate. The antibiotic resistance phenotypes observed in the isolates and the presence of β-lactamases genes detected in some isolates are of clinical and public health concern as this has consequences for antimicrobial chemotherapy of infections associated with Aeromonas species. This study further supports wastewater as potential reservoirs of antibiotic resistance determinants in the environment. Isoken H. Igbinosa and Anthony I. Okoh Copyright © 2012 Isoken H. Igbinosa and Anthony I. Okoh. All rights reserved. Collaboration between HPMC and NaCMC in order to Reach the Polymer Critical Point in Theophylline Hydrophilic Matrices Wed, 01 Aug 2012 09:14:43 +0000 Percolation theory has been applied in order to study the existence of critical points as well as the possibility to find a “combined percolation threshold” for ternary hydrophilic matrices prepared with HPMC, NaCMC, and theophylline. For this purpose, different batches of ternary as well as binary hydrophilic matrices have been prepared. Critical points have been found for binary hydrophilic matrices between 21.5 and 31.3% (v/v) of HPMC and between 39 and 54% (v/v) of NaCMC, respectively. In a previous work carried out with the same polymers but a much more soluble drug (KCl), it was demonstrated the existence of a partial collaboration between the polymers in order to establish the gel layer. In this work, it has been observed for the first time the need of a minimum concentration of one of the matrix-forming polymer (between 10 and 20% v/v, approximately) for establishing an effective collaboration. L. Contreras, L. M. Melgoza, A. Aguilar-de-Leyva, and I. Caraballo Copyright © 2012 L. Contreras et al. All rights reserved. In Vitro Evaluation of Antiprotozoal and Antiviral Activities of Extracts from Argentinean Mikania Species Tue, 31 Jul 2012 10:48:15 +0000 The aim of this study was to investigate the antiprotozoal and antiviral activities of four Argentinean Mikania species. The organic and aqueous extracts of Mikania micrantha, M. parodii, M. periplocifolia, and M. cordifolia were tested on Trypanosoma cruzi epimastigotes, Leishmania braziliensis promastigotes, and dengue virus type 2. The organic extract of M. micrantha was the most active against T. cruzi and L. braziliensis exhibiting a growth inhibition of 77.6±4.5% and 84.9±6.1%, respectively, at a concentration of 10 μg/ml. The bioguided fractionation of M. micrantha organic extract led to the identification of two active fractions. The chromatographic profile and infrared analysis of these fractions revealed the presence of sesquiterpene lactones. None of the tested extracts were active against dengue virus type 2. Laura C. Laurella, Fernanda M. Frank, Andrea Sarquiz, María R. Alonso, Gustavo Giberti, Lucia Cavallaro, Cesar A. Catalán, Silvia I. Cazorla, Emilio Malchiodi, Virginia S. Martino, and Valeria P. Sülsen Copyright © 2012 Laura C. Laurella et al. All rights reserved. Design Space Approach in Optimization of Fluid Bed Granulation and Tablets Compression Process Tue, 31 Jul 2012 08:52:03 +0000 The aim of this study was to optimize fluid bed granulation and tablets compression processes using design space approach. Type of diluent, binder concentration, temperature during mixing, granulation and drying, spray rate, and atomization pressure were recognized as critical formulation and process parameters. They were varied in the first set of experiments in order to estimate their influences on critical quality attributes, that is, granules characteristics (size distribution, flowability, bulk density, tapped density, Carr's index, Hausner's ratio, and moisture content) using Plackett-Burman experimental design. Type of diluent and atomization pressure were selected as the most important parameters. In the second set of experiments, design space for process parameters (atomization pressure and compression force) and its influence on tablets characteristics was developed. Percent of paracetamol released and tablets hardness were determined as critical quality attributes. Artificial neural networks (ANNs) were applied in order to determine design space. ANNs models showed that atomization pressure influences mostly on the dissolution profile, whereas compression force affects mainly the tablets hardness. Based on the obtained ANNs models, it is possible to predict tablet hardness and paracetamol release profile for any combination of analyzed factors. Jelena Djuriš, Djordje Medarević, Marko Krstić, Ivana Vasiljević, Ivana Mašić, and Svetlana Ibrić Copyright © 2012 Jelena Djuriš et al. All rights reserved. Development and Validation of an RP-HPLC Method for CB13 Evaluation in Several PLGA Nanoparticle Systems Mon, 18 Jun 2012 10:28:24 +0000 A simple, fast, and reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed and validated for determining of a cannabinoid derivate, which displays potent antihyperalgesic activity, 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) into PLGA nanoparticles. Separation was achieved in a C18 column using a mobile phase consisting of two solvents: solvent A, consisting of acetonitrile : water : acetic acid (75 : 23.7 : 1.3 v/v), and solvent B, consisting of acetonitrile. An isocratic method (70 : 30 v/v), with a flow rate of 1.000 mL/min, and a diode array detector were used. The developed method was precise, accurate, and linear over the concentration range of analysis with a limit of detection and a limit of quantification of 0.5 and 1.25 μg/mL, respectively. The developed method was applied to the analysis of CB13 in nanoparticles samples obtained by three different procedures (SEV, FF, and NPP) in terms of encapsulation efficiency and drug release. Nanoparticles size and size distribution were also evaluated founding that NPP method presented the most lowest particle sizes with narrow-size distribution (≈320 nm) and slightly negative zeta potential (≈−25 mV) which presumes a suitable procedure for the synthesis of PLGA-CB13 nanoparticles for oral administration. J. Álvarez-Fuentes, L. Martín-Banderas, I. Muñoz-Rubio, M. A. Holgado, and M. Fernández-Arévalo Copyright © 2012 J. Álvarez-Fuentes et al. All rights reserved. Total Flavonoids Content in the Raw Material and Aqueous Extractives from Bauhinia monandra Kurz (Caesalpiniaceae) Mon, 04 Jun 2012 16:02:05 +0000 The aim of this work was to evaluate the spectrophotometric methodology for determining the total flavonoid content (TFC) in herbal drug and derived products from Bauhinia monandra Kurz. Several analytical parameters from this method grounded on the complex formed between flavonoids and AlCl3 were evaluated such as herbal amount (0.25 to 1.25 g); solvent composition (ethanol 40 to 80%, v/v); as well as the reaction time and AlCl3 concentration (2 to 9%, w/v). The method was adjusted to aqueous extractives and its performance studied through precision, linearity and preliminary robustness. The results showed an important dependence of the method response from reaction time, AlCl3 concentration, sample amount, and solvent mixture. After choosing the optimized condition, the method was applied for the matrixes (herbal material and extractives), showing precision lower than 5% (for both parameters repeatability and intermediate precision), coefficient of determination higher than 0.99, and no important influence could be observed for slight variations from wavelength or AlCl3 concentration. Thus, it could be concluded that the evaluated analytical procedure was suitable to quantify the total flavonoid content in raw material and aqueous extractives from leaves of B. monandra. Ana Josane Dantas Fernandes, Magda Rhayanny Assunção Ferreira, Karina Perrelli Randau, Tatiane Pereira de Souza, and Luiz Alberto Lira Soares Copyright © 2012 Ana Josane Dantas Fernandes et al. All rights reserved. General Analytical Schemes for the Characterization of Pectin-Based Edible Gelled Systems Thu, 03 May 2012 08:23:48 +0000 Pectin-based gelled systems have gained increasing attention for the design of newly developed food products. For this reason, the characterization of such formulas is a necessity in order to present scientific data and to introduce an appropriate finished product to the industry. Various analytical techniques are available for the evaluation of the systems formulated on the basis of pectin and the designed gel. In this paper, general analytical approaches for the characterization of pectin-based gelled systems were categorized into several subsections including physicochemical analysis, visual observation, textural/rheological measurement, microstructural image characterization, and psychorheological evaluation. Three-dimensional trials to assess correlations among microstructure, texture, and taste were also discussed. Practical examples of advanced objective techniques including experimental setups for small and large deformation rheological measurements and microstructural image analysis were presented in more details. Maryam Haghighi and Karamatollah Rezaei Copyright © 2012 Maryam Haghighi and Karamatollah Rezaei. All rights reserved. Production of Gymnemic Acid Depends on Medium, Explants, PGRs, Color Lights, Temperature, Photoperiod, and Sucrose Sources in Batch Culture of Gymnema sylvestre Wed, 02 May 2012 17:56:12 +0000 Gymnema sylvestre (R.Br.) is an important diabetic medicinal plant which yields pharmaceutically active compounds called gymnemic acid (GA). The present study describes callus induction and the subsequent batch culture optimization and GA quantification determined by linearity, precision, accuracy, and recovery. Best callus induction of GA was noticed in MS medium combined with 2,4-D (1.5 mg/L) and KN (0.5 mg/L). Evaluation and isolation of GA from the calluses derived from different plant parts, namely, leaf, stem and petioles have been done in the present case for the first time. Factors such as light, temperature, sucrose, and photoperiod were studied to observe their effect on GA production. Temperature conditions completely inhibited GA production. Out of the different sucrose concentrations tested, the highest yield (35.4 mg/g d.w) was found at 5% sucrose followed by 12 h photoperiod (26.86 mg/g d.w). Maximum GA production (58.28 mg/g d.w) was observed in blue light. The results showed that physical and chemical factors greatly influence the production of GA in callus cultures of G. sylvestre. The factors optimized for in vitro production of GA during the present study can successfully be employed for their large-scale production in bioreactors. A. Bakrudeen Ali Ahmed, A. S. Rao, M. V. Rao, and Rosna Mat Taha Copyright © 2012 A. Bakrudeen Ali Ahmed et al. All rights reserved. Novel Ecdysteroids from Serratula wolffii Wed, 02 May 2012 15:01:53 +0000 Two new and one known ecdysteroids were identified in the methanolic extract of the roots of Serratula wolffii. The new compounds isolated were ponasterone A-22-apioside (1) and 3-epi-shidasterone (3), together with the known 3-epi-22-deoxy-20-hydroxyecdysone (2). The structures of compounds 1–3 were determined by extensive spectroscopic techniques, including one- and two-dimensional NMR methods. Attila Ványolós, Zoltán Béni, Miklós Dékány, András Simon, and Mária Báthori Copyright © 2012 Attila Ványolós et al. All rights reserved. Preparation and In Vitro Evaluation of Tacrolimus-Loaded Ethosomes Wed, 02 May 2012 13:52:56 +0000 The main objective of the present work was to prepare and assess dermal delivery of tacrolimus-loaded ethosomes versus classic liposomes. Both delivery systems were characterized for particle size, polydispersity index, and entrapment efficiency (EE), by dynamic laser diffraction and ultrafiltration or dialysis methods, respectively. The results indicated that presence of ethanol in the formulations affected the particle size. In addition, ultrafiltration method was selected to determine EE due to relatively short period as compared with dialysis method. Ethosomes exhibited a significant higher EE and amount of drug in dermis in contrast to classic liposomes suggesting that ethosomes with higher entrapment capacity prompted more amount of tacrolimus to permeate through stratum corneum and reach the target of atopic dermatitis (AD). Physical stability was very well for tacrolimus-loaded ethosomes under storage condition (4°C). Our results demonstrated that the ethosomal system might be a promising candidate for dermal delivery of tacrolimus for AD. Guiling Li, Chao Fan, Xinru Li, Yating Fan, Xiaoning Wang, Mei Li, and Yan Liu Copyright © 2012 Guiling Li et al. All rights reserved. Synthesis and Neuropharmacological Evaluation of Some Novel Quinoxaline 2, 3-Dione Derivatives Wed, 02 May 2012 11:53:44 +0000 Quinoxaline-2, 3-dione obtained from cyclocondensation reaction of o-phenylene diamine with oxalic acid was reacted with three different ketones and formaldehyde to give the corresponding Mannich bases in satisfactory yield. Their structures were confirmed by using 1H NMR, IR, and mass analysis. In pharmacological evaluation, the synthesized compounds showed its curative effect against ethidium-bromide-induced demyelination in rats. For the purpose, different screening methods such as open field exploratory behavior test, rota rod test, grip strength test, beam walk test, and photo actometer test were performed. Ethidium bromide induction showed muscle weakness; muscle discoordination; loss of locomotor activity, and so forth, the synthesized drugs reversed all the above-mentioned neuromuscular disorders caused by ethidium bromide administration. Selvaraj Jubie, Rajamanickam Gayathri, and Rajagopal Kalirajan Copyright © 2012 Selvaraj Jubie et al. All rights reserved. Robust Optimization of Alginate-Carbopol 940 Bead Formulations Tue, 01 May 2012 19:03:28 +0000 Formulation process is a very complex activity which sometimes implicates taking decisions about parameters or variables to obtain the best results in a high variability or uncertainty context. Therefore, robust optimization tools can be very useful for obtaining high quality formulations. This paper proposes the optimization of different responses through the robust Taguchi method. Each response was evaluated like a noise variable, allowing the application of Taguchi techniques to obtain a response under the point of view of the signal to noise ratio. A 𝐿18 Taguchi orthogonal array design was employed to investigate the effect of eight independent variables involved in the formulation of alginate-Carbopol beads. Responses evaluated were related to drug release profile from beads (𝑡50% and AUC), swelling performance, encapsulation efficiency, shape and size parameters. Confirmation tests to verify the prediction model were carried out and the obtained results were very similar to those predicted in every profile. Results reveal that the robust optimization is a very useful approach that allows greater precision and accuracy to the desired value. J. M. López-Cacho, Pedro L. González-R, B. Talero, A. M. Rabasco, and M. L. González-Rodríguez Copyright © 2012 J. M. López-Cacho et al. All rights reserved. Tautomerism in 11-Hydroxyaklavinone: A DFT Study Tue, 01 May 2012 15:59:50 +0000 The antharquinone-based chromophore of 11-hydroxyaklavinone is present in the structure of an anticancer agent, daunomycin. On the other hand, aklavinone is the parent aglycone of certain anthracycline antibiotics that possess anti-cancer activity too. The structures of aklavinone and its 11-hydroxy derivative have many –OH groups, and two keto groups which may take place in certain tautomeric equilibria. Of these tautomeric forms, presently the one involving the anthraquinone based tautomers of 11-hydroxyaklavinone has been investigated quantum chemically in the framework of the density functional theory at the levels of RB3LYP/6-31G(d) and RB3LYP/6-31G(d,p). Lemi Türker Copyright © 2012 Lemi Türker. All rights reserved. PHBV/PCL Microparticles for Controlled Release of Resveratrol: Physicochemical Characterization, Antioxidant Potential, and Effect on Hemolysis of Human Erythrocytes Tue, 01 May 2012 15:57:11 +0000 Microparticles of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) containing resveratrol were successfully prepared by simple emulsion/solvent evaporation. All formulations showed suitable encapsulation efficiency values higher than 80%. PHBV microparticles revealed spherical shape with rough surface and presence of pores. PCL microparticles were spherically shaped with smooth surface. Fourier-transformed infrared spectra demonstrated no chemical bond between resveratrol and polymers. X-ray powder diffraction patterns and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. These PHBV/PCL microparticles delayed the dissolution profile of resveratrol. Release profiles were better fitted to biexponential equation. The hypochlorous-acid-scavenging activity and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation discoloration assay confirmed that the antioxidant activity of PHBV/PCL microparticles was kept, but was dependent on the microparticle morphology and dissolution profile. Resveratrol-loaded PHBV/PCL microparticles showed no cytotoxic effect on red blood cells. Jessica Bitencourt Emilio Mendes, Manoela Klüppel Riekes, Viviane Matoso de Oliveira, Milton Domingos Michel, Hellen Karine Stulzer, Najeh Maissar Khalil, Sônia Faria Zawadzki, Rubiana Mara Mainardes, and Paulo Vitor Farago Copyright © 2012 Jessica Bitencourt Emilio Mendes et al. All rights reserved. Microbial Transformations of 7-Hydroxyflavanone Mon, 30 Apr 2012 13:36:34 +0000 Microbial transformations of racemic 7-hydroxyflavanone using strains of genus Aspergillus (A. niger KB, A. niger 13/5, A. ochraceus 456) and the species Penicillium chermesinum 113 were studied. The products of O-methylation, O-methylation along with hydroxylation at C-3′ and C-4′, reduction of the carbonyl group, reduction of the carbonyl group along with hydroxylation at C-5, and dehydrogenation of C-2 and C-3 were obtained. Most of the products (with the exception of the O-methylation one) have stronger antioxidant properties than the initial substrate. Edyta Kostrzewa-Susłow and Tomasz Janeczko Copyright © 2012 Edyta Kostrzewa-Susłow and Tomasz Janeczko. All rights reserved. Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation Sun, 29 Apr 2012 15:40:18 +0000 The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC) and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P) ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP) as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant temperature of 37∘C±0.1. Similarity factor 𝑓2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including 𝐶max, 𝑇max and AUC0-𝑡 were compared which showed an optimized 𝐶max and 𝑇max (𝑃<0.05). A good correlation was obtained between in vitro drug release and in vivo drug absorption with correlation value (𝑅2=0.934). Relative bioavailability was found to be 93%. Reproducibility of manufacturing process and accelerated stability of the developed tablets were performed in stability chamber at 40±2∘C and 75±5% relative humidity for a period of 6 months and were found to be stable throughout the stability period. Kifayat Ullah Shah and Gul Majid Khan Copyright © 2012 Kifayat Ullah Shah and Gul Majid Khan. All rights reserved. A Study on Solubilization of Poorly Soluble Drugs by Cyclodextrins and Micelles: Complexation and Binding Characteristics of Sulfamethoxazole and Trimethoprim Sun, 29 Apr 2012 10:19:38 +0000 The present study is focused on the characterization of solubilization of poorly soluble drugs, that is, sulfamethoxazole (SMX) and trimethoprim (TMP) by cyclodextrins (α-, β-, and γ-CDs) and anionic surfactant sodium dodecyl sulfate (SDS). The phase solubility diagrams drawn from UV spectral measurements are of the AL type and indicate an enhancement of SMX and TMP solubility in the presence of CDs. Complex formation tendency of TMP with CDs followed the order: γ-CD > β-CD > α-C. However, the complex formation constant values, for SMX-CD system yielded the different affinity and follow the order: β-CD > γ-CD > α-CD. With taking into consideration of solubilization capacity of SDS micelles, it has been found that the solubility enhancement of TMP is much higher than that of SMX in the presence of SDS micelles. The binding constants of SMX and TMP obtained from the Benesi-Hildebrand equation are also confirmed by the estimated surface properties of SDS, employing the surface tension measurements. In order to elucidate the solubilization characteristics the surface tension measurements were also performed for nonionic surfactant Triton X-100. Polarity of the microenvironment and probable location of SMX and TMP were also discussed in the presence of various organic solvents. Sinem Göktürk, Elif Çalışkan, R. Yeşim Talman, and Umran Var Copyright © 2012 Sinem Göktürk et al. All rights reserved. Temperature-Sensitive Gels for Intratumoral Delivery of β-Lapachone: Effect of Cyclodextrins and Ethanol Tue, 24 Apr 2012 11:40:55 +0000 This work evaluated the potential of Pluronics (varieties F127 and P123) in combination with solubilizing agents to be used as syringeable in situ gelling depots of intratumoral β-lapachone (βLAP). Pluronic dispersions prepared at various concentrations in the absence and the presence of ethanol and randomly methylated β-cyclodextrin (RMβCD) were characterized regarding their rheological properties, drug solubilization capacity, and in vitro release. Pluronic F127 (18–23%) formulations combined high ability to solubilize βLAP (enhancement solubility factor up to 50), adequate gel temperature range (over 25°C), and gel strength at 37°C enough to guarantee the permanence of the formulation in the administration site for a period of time. βLAP release rate was finely tuned by the concentration of the polymer and the addition of RMβCD (diffusion coefficient ranging between 9 and 69 μg·cm−2). The ethanol increases βLAP release rate but simultaneously led to weak gels. This paper shows that βLAP formulations involving temperature-reversible Pluronic gels may be suitable for intratumoral drug delivery purposes. Marcilio S. S. Cunha-Filho, Carmen Alvarez-Lorenzo, Ramón Martínez-Pacheco, and Mariana Landin Copyright © 2012 Marcilio S. S. Cunha-Filho et al. All rights reserved. Simple Reversed-Phase HPLC Method with Spectrophotometric Detection for Measuring Acetaminophen-Protein Adducts in Rat Liver Samples Thu, 19 Apr 2012 13:09:00 +0000 A simple reversed-phase HPLC method for measuring hepatic levels of acetaminophen- (APAP-) protein adduct following an overdose of APAP was developed. An aliquot of liver homogenate in phosphate-buffered saline pH 7.4 (PBS) was placed on a Nanosep centrifugal device, which was centrifuged to obtain a protein residue. This residue was incubated with a solution of p-aminobenzoic acid (PABA), the internal standard, and bacterial protease in PBS, transferred to a Nanosep centrifugal device, and centrifuged. A 100 μL portion of the filtrate was analyzed on a YMC-Pack ODS-AMQ C18 column, using 100 mM potassium dihydrogen phosphate-methanol-acetic acid (100 : 0.6 : 0.1) as the mobile phase, a flow rate of 1 mL/min, and photometric detection at 254 nm. PABA and APAP-cystein-S-yl (APAP-Cys) eluted at ~14.7 min and 22.7 min, respectively. Method linearity, based on on-column concentrations of APAP-Cys, was observed over the range 0.078–40 μg. Recoveries of APAP-Cys from spiked blank liver homogenates ranged from ~83% to 91%. Limits of detection and of quantification of APAP-Cys, based on column concentrations, were 0.06 μg and 0.14 μg, respectively. RSD values for interday and intraday analyses of a blank liver homogenate spiked with APAP-Cyst at three levels were, in all cases, ≤1.0% and <1.5%, respectively. The proposed method was found appropriate for comparing the antidotal properties of N-acetylcysteine and taurine in a rat model of APAP poisoning. Miteshkumar Acharya and Cesar A. Lau-Cam Copyright © 2012 Miteshkumar Acharya and Cesar A. Lau-Cam. All rights reserved. Docking Studies, Synthesis, Characterization and Evaluation of Their Antioxidant and Cytotoxic Activities of Some Novel Isoxazole-Substituted 9-Anilinoacridine Derivatives Thu, 19 Apr 2012 11:10:53 +0000 A convenient synthesis of novel isoxazole-substituted 9-anilinoacridine derivatives 5a–j was reported. The compounds were confirmed by physical and analytical data and screened for in vitro antioxidant activity by DPPH method, reducing power assay and total antioxidant capacity method. The cytotoxic activity of the compounds was also studied in HEp-2 cell line. The docking studies of the synthesized compounds were performed towards the key nucleoside dsDNA by using AutoDock vina 4.0 programme. All the isoxazole-substituted compounds have significant activities. R. Kalirajan, M. H. Mohammed Rafick, S. Sankar, and S. Jubie Copyright © 2012 R. Kalirajan et al. All rights reserved. Effect of Potent Ethyl Acetate Fraction of Stereospermum suaveolens Extract in Streptozotocin-Induced Diabetic Rats Thu, 19 Apr 2012 10:57:30 +0000 To evaluate the antihyperglycemic effect of ethyl acetate fraction of ethanol extract of Stereospermum suaveolens in streptozotocin-(STZ-) induced diabetic rats by acute and subacute models. In this paper, various fractions of ethanol extract of Stereospermum suaveolens were prepared and their effects on blood glucose levels in STZ-induced diabetic rats were studied after a single oral administration (200?mg/kg). Administration of the ethyl acetate fraction at 200?mg/kg once daily for 14 days to STZ-induced diabetic rats was also carried out. The parameters such as the fasting blood glucose, hepatic glycogen content, and pancreatic antioxidant levels were monitored. In the acute study, the ethyl acetate fraction is the most potent in reducing the fasting serum glucose levels of the STZ-induced diabetic rats. The 14-day repeated oral administration of the ethyl acetate fraction significantly reduced the fasting blood glucose and pancreatic TBARS level and significantly increased the liver glycogen, pancreatic superoxide dismutase, and catalase activities as well as reduced glutathione levels. The histopathological studies during the subacute treatment have been shown to ameliorate the STZ-induced histological damage of pancreas. This paper concludes that the ethyl acetate fraction from ethanol extract of Stereospermum suaveolens possesses potent antihyperglycemic and antioxidant properties, thereby substantiating the use of plant in the indigenous system of medicine. T. Balasubramanian, Tapan Kumar Chatterjee, G. P. Senthilkumar, and Tamizh Mani Copyright © 2012 T. Balasubramanian et al. All rights reserved. In Vitro Conservation of Twenty-Three Overexploited Medicinal Plants Belonging to the Indian Sub Continent Thu, 19 Apr 2012 10:56:39 +0000 Twenty-three pharmaceutically important plants, namely, Elaeocarpus spharicus, Rheum emodi, Indigofera tinctoria, Picrorrhiza kurroa, Bergenia ciliata, Lavandula officinalis, Valeriana wallichii, Coleus forskohlii, Gentiana kurroo, Saussurea lappa, Stevia rebaudiana, Acorus calamus, Pyrethrum cinerariaefolium, Aloe vera, Bacopa monnieri, Salvia sclarea, Glycyrrhiza glabra, Swertia cordata, Psoralea corylifolia, Jurinea mollis, Ocimum sanctum, Paris polyphylla, and Papaver somniferum, which are at the verge of being endangered due to their overexploitation and collection from the wild, were successfully established in vitro. Collections were made from the different biodiversity zones of India including Western Himalaya, Northeast Himalaya, Gangetic plain, Western Ghats, Semiarid Zone, and Central Highlands. Aseptic cultures were raised at the morphogenic level of callus, suspension, axillary shoot, multiple shoot, and rooted plants. Synseeds were also produced from highly proliferating shoot cultures of Bacopa monnieri, Glycyrrhiza glabra, Stevia rebaudiana, Valeriana wallichii, Gentiana kurroo, Lavandula officinalis, and Papaver somniferum. In vitro flowering was observed in Papaver somniferum, Psoralea corylifolia, and Ocimum sanctum shoots cultures. Out of 23 plants, 18 plants were successfully hardened under glasshouse conditions. Priyanka Verma, Ajay Kumar Mathur, Sheetal Prasad Jain, and Archana Mathur Copyright © 2012 Priyanka Verma et al. All rights reserved. Lithium-Acetate-Mediated Biginelli One-Pot Multicomponent Synthesis under Solvent-Free Conditions and Cytotoxic Activity against the Human Lung Cancer Cell Line A549 and Breast Cancer Cell Line MCF7 Thu, 19 Apr 2012 10:33:12 +0000 Various Biginelli compounds (dihydropyrimidinones) have been synthesized efficiently and in high yields under mild, solvent-free, and eco-friendly conditions in a one-pot reaction of 1,3-dicarbonyl compounds, aldehydes, and urea/thiourea/acetyl thiourea using lithium-acetate as a novel catalyst without the addition of any proton source. Comparative catalytic efficiency of lithium-acetate and polyphosphoric acid to catalyze Biginelli condensation is also studied under neat conditions. The reaction is carried out in the absence of any solvent and represents an improvement of the classical Biginelli protocol and an advantage in comparison with FeCl3·6H2O, NiCl2·6H2O and CoCl2·6H2O that were used with HCl as a cocatalyst. Compared to classical Biginelli reaction conditions, the present method has advantages of good yields, short reaction times, and experimental simplicity. The obtained products have been identified by spectral (1H NMR and IR) data and their melting points. The prepared compounds are evaluated for anticancer activity against two human cancer cell lines (lung cancer cell line A549 and breast cancer cell line MCF7). Harshita Sachdeva and Diksha Dwivedi Copyright © 2012 Harshita Sachdeva and Diksha Dwivedi. All rights reserved. Improvement of the Bioavailability and Glycaemic Metabolism of Cinnamon Oil in Rats by Liquid Loadable Tablets Sun, 01 Apr 2012 08:02:42 +0000 The purpose of this study is to investigate the bioavailability and glycaemic metabolism of cinnamon oil (CIO) carried by liquid-loadable tablets (CIO-LLTs), the carrier of a CIO self-emulsifying formulation (CIO-LS). The results of tests performed to evaluate the physical properties of the CIO-LLT complied with Chinese Pharmacopeia (2010). The release profile suggested that the CIO-LLT preserved the enhancement of in vitro dissolution of cio. After orally administration, the plasma concentration-time profile and pharmacokinetic parameters suggested that a significant increase (𝑃<0.0001) in the 𝐶max, AUC and F were observed in the CIO-LLT. The blood glucose and the HbA1c were significantly decreased in alloxan-induced hyperglycemic rats (𝑃<0.05, 𝑃<0.01, resp.), while the level of insulin secretion was markedly elevated in alloxan-induced hyperglycemic rats (𝑃<0.05). The alloxan-damaged pancreatic 𝛽-cells of the rats were partly recovered gradually after the rats were administered with CIO-LLT 45 days later. CIO-LLT could improve the bioavailability and glycaemic metabolism of CIO. Chunchao Han and Bo Cui Copyright © 2012 Chunchao Han and Bo Cui. All rights reserved. Influence of the Flexible Liposomes on the Skin Deposition of a Hydrophilic Model Drug, Carboxyfluorescein: Dependency on Their Composition Mon, 12 Mar 2012 15:43:51 +0000 This study focuses on the effect of different flexible liposomes containing sodium cholate, Tween 80, or cineol on skin deposition of carboxyfluorescein (CF). Size distribution, morphology, zeta potential, and stability of the prepared vesicles were evaluated. The influence of these systems on the skin deposition of CF utilizing rat skin as membrane model was investigated. Results showed that all of the investigated liposomes had almost spherical shapes with low polydispersity (PDI < 0.3) and particles size range from 83 to 175 nm. All liposomal formulations exhibited negative zeta potential, good drug entrapment efficiency, and stability. In vitro skin deposition data showed that flexible liposomes gave significant deposition of CF on the skin compared to conventional liposomes and drug solutions. This study revealed that flexible liposomes, containing cineole, were able to deliver higher amount of CF suggesting that the hydrophilic drugs delivery to the skin was strictly correlated to the vesicle composition. Mohamed Badran, Khaled Shalaby, and Abdullah Al-Omrani Copyright © 2012 Mohamed Badran et al. All rights reserved. A Novel Murine Model for the In Vivo Study of Transdermal Drug Penetration Wed, 04 Jan 2012 10:58:09 +0000 Enhancement of the transdermal penetration of different active agents is an important research goal. Our aim was to establish a novel in vivo experimental model which provides a possibility for exact measurement of the quantity of penetrated drug. The experiments were performed on SKH-1 hairless mice. A skin fold in the dorsal region was fixed with two fenestrated titanium plates. A circular wound was made on one side of the skin fold. A metal cylinder with phosphate buffer was fixed into the window of the titanium plate. The concentration of penetrated drug was measured in the buffer. The skin fold was morphologically intact and had a healthy microcirculation. The drug appeared in the acceptor buffer after 30 min, and its concentration exhibited a continuous increase. The presence of ibuprofen was also detected in the plasma. In conclusion, this model allows an exact in vivo study of drug penetration and absorption. Gábor Erős, Petra Hartmann, Szilvia Berkó, Eszter Csizmazia, Erzsébet Csányi, Anita Sztojkov-Ivanov, István Németh, Piroska Szabó-Révész, István Zupkó, and Lajos Kemény Copyright © 2012 Gábor Erős et al. All rights reserved. Candidate Gene in Predicting In Vivo Ovarian Cancer Response to Combination Therapy with Paraplatin and Paclitaxel Mon, 01 Jan 1900 00:00:00 +0000 Ramin Mirhashemi, J. Fernando Arena, Tony Frudakis, Nicholas Lambrou, Jane Arboleda, Marsha Hunt, Maria Medranda, Hervy Averette, and Manuel Penalver Copyright © 2002 Ramin Mirhashemi et al. All rights reserved. 8-Chloro-cAMP-Related Changes on Mice Uteri Mon, 01 Jan 1900 00:00:00 +0000 Histopathological effects of cAMP analog (8-Chloro-cAMP), tamoxifen, and medroxyprogesterone, alone or combined, upon BALB/c mice uteri are reported. 8-Chloro-cAMP diminished uterine weight, but did not modify its histopathology or estral cycle significantly. Tamoxifen diminished uterine weight showing cystic hyperplasia and an estral cycle arrested at diestrus. Medroxyprogesterone increased uterine weight, caused a swelling of the endometrium and a pseudopregnancy estrus. When combined with 8-Chloro-cAMP, tamoxifen or medroxyprogesterone always had a predominant effect. We concluded that the effects of 8-Chloro-cAMP on mice uteri did not cause significant changes on its histopathology, but diminished its weight. Andrea Actis, Maximo Croci, Emanuel Levin, and Rosa Bergoc Copyright © 2002 Andrea Actis et al. All rights reserved. Metallic Magnetic Nanoparticles Mon, 01 Jan 1900 00:00:00 +0000 In this paper, we reviewed some relevant aspects of the magnetic properties of metallic nanoparticles with small size (below 4 nm), covering the size effects in nanoparticles of magnetic materials, as well as the appearance of magnetism at the nanoscale in materials that are nonferromagnetic in bulk. These results are distributed along the text that has been organized around three important items: fundamental magnetic properties, different fabrication procedures, and characterization techniques. A general introduction and some experimental results recently obtained in Pd and Au nanoparticles have also been included. Finally, the more promising applications of magnetic nanoparticles in biomedicine are indicated. Special care was taken to complete the literature available on the subject. A. Hernando, P. Crespo, and M. A. García Copyright © 2005 A. Hernando et al. All rights reserved. Can Drug–Drug Interactions Be Predicted from In Vitro Studies? Mon, 01 Jan 1900 00:00:00 +0000 Potential drug–drug interactions as well as drug–xenobiotic interactions are a major source of clinical problems, sometimes with dramatic consequences. Investigation of drug–drug interactions during drug development is a major concern for the drug companies while developing new drugs. Pierre Kremers Copyright © 2002 Pierre Kremers. All rights reserved. Structural Models for Cytochrome P450�Mediated Catalysis Mon, 01 Jan 1900 00:00:00 +0000 This review focuses on the structural models for cytochrome P450 that are improving our knowledge and understanding of the P450 catalytic cycle, and the way in which substrates bind to the enzyme leading to catalytic conversion and subsequent formation of mono-oxygenated metabolites. Various stages in the P450 reaction cycle have now been investigated using X-ray crystallography and electronic structure calculations, whereas homology modelling of mammalian P450s is currently revealing important aspects of pharmaceutical and other xenobiotic metabolism mediated by P450 involvement. These features are explored in the current review on P450-based catalysis, which emphasises the importance of structural modelling to our understanding of this enzyme's function. In addition, the results of various QSAR analyses on series of chemicals, which are metabolised via P450 enzymes, are presented such that the importance of electronic and other structural factors in explaining variations in rates of metabolism can be appreciated. David F.V. Lewis Copyright © 2003 David F.V.�Lewis. All rights reserved. Differences Between Lovastatin and Simvastatin Hydrolysis in Healthy Male and Female Volunteers: Gut Hydrolysis of Lovastatin is Twice that of Simvastatin Mon, 01 Jan 1900 00:00:00 +0000 The aim of this pharmacokinetic evaluation was to show the effect of the extra methyl group in simvastatin on esterase hydrolysis between lovastatin and simvastatin in male and female volunteers. This study was based on the plasma concentration-time curves and the pharmacokinetics of lovastatin and simvastatin with its respective active metabolite statin-β-hydroxy acid obtained from two different bioequivalence studies, each with 18 females and 18 males. Results were: 1-The group of female volunteers showed a higher yield of the active metabolite β-hydroxy acid than the group of males (p < 0.002) for both lovastatin and simvastatin. This difference was not related to the body weight of both groups. 2-In the male/female groups, subject-dependent yield of active metabolite β-hydroxy acid was demonstrated, which was independent of the formulation. The variation in plasma/liver hydrolysis resulted in a fan-shaped distribution of data points when the AUCt lovastatin was plotted vs. that of the β-hydroxy acid metabolite. In the fan of data points, subgroups could be distinguished, each showing a different regression line and with a different Y-intercept (AUCtβ-hydroxy acid). 3-Lovastatin hydrolysis was higher than simvastatin hydrolysis. 4-It was possible to discriminate between hydrolysis of both lovastatin and simvastatin by plasma/liver or tissue esterase activity. Tom B. Vree, Erik Dammers, Ivan Ulc, Stefan Horkovics-Kovats, Miroslav Ryska, and IJsbrand Merkx Copyright © 2003 Tom B. Vree et al. All rights reserved. Rosiglitazone Add-On in Treatment of Depressed Patients with Insulin Resistance: a Pilot Study Mon, 01 Jan 1900 00:00:00 +0000 A number of cross-sectional studies have suggested an association between insulin resistance (IR) and affective disorders. However, limited data exist on potential changes in IR in a prospective treatment of depression. The present pilot study tested the hypothesis that improvement of IR with the addition of an insulin-sensitizing agent would improve mood in nondiabetic patients with unipolar or bipolar depression, who had surrogate blood markers suggestive of IR. Surrogate IR-criteria blood markers were fasting plasma glucose >100 mg/dl or triglyceride (TG) to high density lipoprotein (HDL) ratio >3.0. Open-label rosiglitazone, titrated to a dose of 8 mg/day, was administered for 12 weeks to 12 patients with depressive disorder receiving treatment as usual (TAU). Eight patients who completed the 12-week study exhibited significant declines in both depression severity by the Hamilton Depression Rating Scale and the Clinical Global Impression scale, with moderate effect sizes noted. Modest improvement in Matsuda Index scores was also noted at 12 weeks, yet declines in depression severity scores were not associated with improvements in the endocrine markers (Matsuda Index, TG/HDL ratio, and body mass index). These results suggest the potential novel use for an insulin-sensitizing agent in the treatment of depressive disorders. Larger placebo-controlled studies are warranted. Natalie L. Rasgon, Heather A. Kenna, Katherine E. Williams, Bevin Powers, Tonita Wroolie, and Alan F. Schatzberg Copyright © 2010 Natalie L. Rasgon et al. All rights reserved. New Therapeutic Targets for Mood Disorders Mon, 01 Jan 1900 00:00:00 +0000 Existing pharmacological treatments for bipolar disorder (BPD) and major depressive disorder (MDD) are often insufficient for many patients. Here we describe a number of targets/compounds that clinical and preclinical studies suggest could result in putative novel treatments for mood disorders. These include: (1) glycogen synthase kinase-3 (GSK-3) and protein kinase C (PKC), (2) the purinergic system, (3) histone deacetylases (HDACs), (4) the melatonergic system, (5) the tachykinin neuropeptides system, (6) the glutamatergic system, and (7) oxidative stress and bioenergetics. The paper reviews data on new compounds that have shown antimanic or antidepressant effects in subjects with mood disorders, or similar effects in preclinical animal models. Overall, an improved understanding of the neurobiological underpinnings of mood disorders is critical in order to develop targeted treatments that are more effective, act more rapidly, and are better tolerated than currently available therapies. Rodrigo Machado-Vieira, Giacomo Salvadore, Nancy DiazGranados, Lobna Ibrahim, David Latov, Cristina Wheeler-Castillo, Jacqueline Baumann, Ioline D. Henter, and Carlos A. Zarate Copyright © 2010 Rodrigo Machado-Vieira et al. All rights reserved. Pharmaceutical Compounds in Wastewater: Wetland Treatment as a Potential Solution Mon, 01 Jan 1900 00:00:00 +0000 Pharmaceutical compounds are being released into the aquatic environment through wastewater discharge around the globe. While there is limited removal of these compounds within wastewater treatment plants, wetland treatment might prove to be an effective means to reduce the discharge of the compounds into the environment. Wetlands can promote removal of these pharmaceutical compounds through a number of mechanisms including photolysis, plant uptake, microbial degradation, and sorption to the soil. We review relevant laboratory research on these various mechanisms and provide data on the few studies that have examined wetland removal. There is a need to document the degree to which various pharmaceutical compounds are removed in full-scale treatment wetlands, as there is a paucity of data on overall pharmaceutical removal rates. John R. White, Marco A. Belmont, and Chris D. Metcalfe Copyright © 2006 John R. White et al. All rights reserved. The Use of Spreadsheets for Pharmacokinetic Simulations Mon, 01 Jan 1900 00:00:00 +0000 The use of simple spreadsheets is described to create simulations of complex pharmacokinetic phenomena. The basics of spreadsheets are first described and are developed to demonstrate classical pharmacokinetics without the use of differential or integral calculus. Using standard spreadsheet commands, the technique is shown to be applicable to the full range of advanced pharmacokinetic simulations. Demonstrations of the effect of a variety of physiological eventualities are included to show the versatility of the technique. The technique is very simple to use and is always in the complete control of the modeller. Joseph Chamberlain Copyright © 2003 Joseph Chamberlain. All rights reserved. Molecular Binding Interactions: Their Estimation and Rationalization in QSARs in Terms of Theoretically Derived Parameters Mon, 01 Jan 1900 00:00:00 +0000 An extensive survey of molecular binding interactions and parameters used in QSARs is reported, which includes consideration of lipophilicity and the derivation of Linear Free Energy Relationships associated with drug-receptor binding, together with an overview of the various contributions to binding energy. The lipophilic parameter, log P, and its relevance to desolvation energy is outlined and explanation of the parameters derived from electronic structure calculation is provided, leading into a summary of molecular dynamics simulations. David F.V. Lewis and Howard B. Broughton Copyright © 2002 David F.V. Lewis and Howard B. Broughton. All rights reserved. Comparison of Quantitative Structure-Activity Relationship Model Performances on Carboquinone Derivatives Mon, 01 Jan 1900 00:00:00 +0000 Quantitative structure-activity relationship (qSAR) models are used to understand how the structure and activity of chemical compounds relate. In the present study, 37 carboquinone derivatives were evaluated and two different qSAR models were developed using members of the Molecular Descriptors Family (MDF) and the Molecular Descriptors Family on Vertices (MDFV). The usual parameters of regression models and the following estimators were defined and calculated in order to analyze the validity and to compare the models: Akaike?s information criteria (three parameters), Schwarz (or Bayesian) information criterion, Amemiya prediction criterion, Hannan-Quinn criterion, Kubinyi function, Steiger's Z test, and Akaike's weights. The MDF and MDFV models proved to have the same estimation ability of the goodness-of-fit according to Steiger's Z test. The MDFV model proved to be the best model for the considered carboquinone derivatives according to the defined information and prediction criteria, Kubinyi function, and Akaike's weights. Sorana D. Bolboaca and Lorentz Jäntschi Copyright © 2009 Sorana-D Bolboacă and Lorentz Jäntschi. All rights reserved. Treatment of Lowland Frogs From the Spawn Stage with Homeopathically Prepared Thyroxin (10-30) Mon, 01 Jan 1900 00:00:00 +0000 The influence of a highly diluted agitated, i.e. homeopathically prepared thyroxin solution (10-30, final concentration in the basin water 10-35 parts by weight after the first application) on metamorphosis in lowland Rana temporaria from the spawn stage on was studied. The treatment with homeopathically prepared thyroxin solution (10-30) starts at the frogspawn stage. It represents a tool to learn more about the previously standardized amphibian model, where the thyroxin solution was applied from the two- legged stage on only. Lowland frogs were pretreated by immersing spawn in an aqueous molecular thyroxin dilution (10-8 parts by weight). In later stages of development (2 to 4 legged), this has been found to speed up metamorphosis by around 15%. In accordance with the homeopathic idea of detoxication or cure, hyperstimulated animals (spawn or, in subsequence, larvae) were treated either with thyroxin that had been highly diluted and agitated in successive steps, i.e. homeopathically prepared (10-30), or analogously prepared blank solution (water). Development was monitored by documenting the number of animals that had entered the four-legged stage. It has been found that animals treated with the test solution metamorphosed more slowly than the control animals, i.e. the effect of the homeopathically prepared thyroxin was opposed to the usual effect of molecular thyroxin. The number of test animals that reached the 4- legged stage at defined points in time was slightly smaller in the group treated with homeopathically prepared thyroxin at some, but not at all points in time, compared to control. The results in this study sustain the previous multi researcher findings that highly diluted homeopathically prepared thyroxin is able to slow down metamorphosis of Rana temporaria. Helmut Graunke, P. Christian Endler, Waltraud Scherer-Pongratz, Heinz Spranger, Michael Frass, and Harald Lothaller Copyright © 2007 Helmut Graunke et al. All rights reserved. Conditioned Place Preference Induced by Licit Drugs: Establishment, Extinction, and Reinstatement Mon, 01 Jan 1900 00:00:00 +0000 The conditioned place preference (CPP) model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine. Yu Liu, Bernard Le Foll, Yanli Liu, Xi Wang, and Lin Lu Copyright © 2008 Yu Liu et al. All rights reserved. Variable Absorption of Clavulanic Acid After an Oral Dose of 25 mg/kg of Clavubactin® and Synulox® in Healthy Cats Mon, 01 Jan 1900 00:00:00 +0000 The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration-time curves of amoxicillin and clavulanic acid in cats, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration-time curves obtained following a single-dose, open, randomised, two-way crossover phase-I study, each involving 24 female cats treated with two Amoxi-Clav formulations (formulation A was Clavubactin® and formulation was B Synulox® ; 80/20 mg, 24 animals, 48 drug administrations). Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods. The half-life of elimination of amoxicillin is 1.2 h (t1/2 = 1.24 ± 0.28 h, Cmax = 12.8 ± 2.12 μg/ml), and that of clavulanic acid 0.6 h (t1/2 = 0.63 ± 0.16 h, Cmax = 4.60 ± 1.68 μg/ml). There is a ninefold variation in the AUCt of clavulanic acid for both formulations, while the AUCt of amoxicillin varies by a factor of two. The highest clavulanic acid AUCt values indicate the best absorption; all other data indicate less absorption. Taking into account that the amoxicillin–to–clavulanic acid dose ratio in the two products tested was 4:1, the blood concentration ratios may actually vary much more, apparently without compromising the products’ high efficacy against susceptible microorganisms. Tom B. Vree, Eric Dammers, and Eri van Duuren Copyright © 2002 Tom B. Vree et al. All rights reserved. Big Pharma, Big Bucks, and a Big Pile o’ Pigs Mon, 01 Jan 1900 00:00:00 +0000 Nature leads this week with a story about the Bush administration’s surprisingly liberal overtures to Third World countries that want to develop inexpensive AIDS medications. Efforts to unify the European research effort are the focus of Science’s lead article. Copyright © 2001 TheScientificWorldJOURNAL. All rights reserved. The Homeopathic Preparation Neurexan® vs. Valerian for the Treatment of Insomnia: An Observational Study Mon, 01 Jan 1900 00:00:00 +0000 Insomnia is prevalent and complementary therapies are common, but data are lacking on the effectiveness and tolerability of preparations beyond valerian. Here we report on an open-label, prospective cohort study in 89 German centers offering both conventional and complementary therapies. Subjects received the homeopathic preparation Neurexan® or valerian for 28 days. Doses were at physicians' judgments. Sleep duration and latency were evaluated based on patients' sleep diaries over 14 days; sleep quality was evaluated at 28 ± 1 days. A total of 409 subjects were enrolled. The groups were balanced at baseline for age, sex, weight, and sleep disturbances. At day 14, both groups reported improved sleep latency and duration; latency was reduced from baseline by 37.3 ± 36.3 min with Neurexan and by 38.2 ± 38.5 min with valerian. The duration of sleep increased by 2.2 (±1.6) h in the Neurexan group and by 2.0 (±1.5) h in the valerian group. Differences between the groups in improvement on sleep duration were significantly in favor of Neurexan therapy at days 8, 12, and 14. At day 28, quality of sleep was improved in both groups with no significant differences between the treatments. Significantly more patients reported lack of daytime fatigue with Neurexan than with valerian therapies (49% vs. 32%; p < 0.05 for the comparison). For patients favorable towards a CAM-based therapy, Neurexan might be an effective and well-tolerated alternative to conventional valerian-based therapies for the treatment of mild to moderate insomnia. Rainer Waldschütz and Peter Klein Copyright © 2008 Rainer Waldschütz and Peter Klein. All rights reserved. Modulation of Apoptosis As a Therapeutic Strategy Mon, 01 Jan 1900 00:00:00 +0000 Kevin J. Tomaselli Copyright © 2001 Kevin J. Tomaselli. All rights reserved. Elucidation of Protein Structural and Pharmacophore Features Based on Sequence Clustering by Common Neighbor Comparisons Mon, 01 Jan 1900 00:00:00 +0000 Richard Kho, Mark Hansen, Brian Baker, Joe Newman, Daniel S. Sem, Richard Jack, and Hugo Villar Copyright © 2002 Richard Kho et al. All rights reserved.