Journal of Pharmaceutics The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Preparation and In Vitro Evaluation of Ethylcellulose and Polymethacrylate Resins Loaded Microparticles Containing Hydrophilic Drug Thu, 10 Apr 2014 14:13:02 +0000 Objective. The purpose of the recent study was to prepare and estimate sustained release of Ethylcellulose (300 cps) and Eudragit (RS 100 and RL 100) microparticles containing Propranolol hydrochloride used as a treatment of cardiovascular system, especially hypertension. Method. Propranolol hydrochloride was microencapsulated with different polymers (Ethylcellulose, Eudragit RS, and Eudragit RL) using modified hydrophobic (O/O) solvent evaporation method using 1 : 1 combination of acetone and isopropanol as the internal phase. Obtained microparticles were showing higher batch yield with higher encapsulation efficiency. Microparticles were prepared with different ratios of 1 : 1, 1 : 3, 1 : 5, and 1 : 7 (%, wt/wt) using span 80 (%, v/v) as a surfactant. Results. The influence of formulation factors like drug: polymer ratio, internal phase, and type of polymers on obtained microparticles was characterized with respect to particle size distribution, encapsulation efficiency, percentage yield, FTIR, and FE-SEM. Higher encapsulation efficiencies were obtained with various polymers like Ethylcellulose (96.63 ± 0.5) compared to Eudragit RS 100 (83.70 ± 0.6) and RL 100 (89.62 ± 0.6). The in vitro release study was characterized by initial burst. Conclusion. The result of study displays that Ethylcellulose and Eudragit loaded microparticles of Propranolol hydrochloride can be effectively prepared using modified hydrophobic emulsification solvent evaporation technique. Therefore, the modified hydrophobic emulsion technique can also be applied to the preparation of microparticles for low molecular weight and highly water soluble drugs. Satish Pandav and Jitendra Naik Copyright © 2014 Satish Pandav and Jitendra Naik. All rights reserved. Solubility Enhancement of Budesonide and Statistical Optimization of Coating Variables for Targeted Drug Delivery Thu, 10 Apr 2014 07:41:54 +0000 The purpose of the research was to present Budesonide (BUD) as a novel formulation showing improved aqueous solubility, which may decrease variability in and found in inflammatory bowel disease (IBD) patients, and drug targeting to colon. To improve aqueous solubility, solid dispersion (SD) of the BUD with poloxamer 188 was prepared by melting method. Physical characterization of solid dispersion was performed. The SD was used to prepare tablet equivalent to 9 mg of BUD. The tablet was coated with enteric polymers Eudragit S100 and Eudragit L100 to target colon. The ratio of polymers and percentage coating was optimized using statistical design. Variables studied in design were ratio of enteric polymers and the effect of percentage coating on in vitro drug release. Dissolution at different pH showed that drug release in colon could be modified by optimizing the ratio of polymers and percentage coating. The dissolution data showed that the percentage coating and ratio of polymers are very important to get lag time and optimum formulation. The optimized batch from statistical design was kept under accelerated condition for three months. After accelerated stability study, there was no significant change in the drug release. Himanshu Bhatt, Bhargavi Naik, and Abhay Dharamsi Copyright © 2014 Himanshu Bhatt et al. All rights reserved. Recently Investigated Natural Gums and Mucilages as Pharmaceutical Excipients: An Overview Mon, 07 Apr 2014 08:19:01 +0000 Due to advances in drug delivery technology, currently, excipients are included in novel dosage forms to fulfil specific functions and in some cases they directly or indirectly influence the extent and/or rate of drug release and drug absorption. Recent trends towards use of plant based and natural products demand the replacement of synthetic additives with natural ones. Today, the whole world is increasingly interested in natural drugs and excipients. These natural materials have many advantages over synthetic ones as they are chemically inert, nontoxic, less expensive, biodegradable, and widely available. This review discusses majority of the plant-derived polymeric compounds (gums and mucilage’s), their sources, chemical constituents, uses, and some recent investigations as excipients in novel drug delivery systems. Pritam Dinesh Choudhary and Harshal Ashok Pawar Copyright © 2014 Pritam Dinesh Choudhary and Harshal Ashok Pawar. All rights reserved. Fast Disintegrating Combination Tablet of Taste Masked Levocetrizine Dihydrochloride and Montelukast Sodium: Formulation Design, Development, and Characterization Sun, 30 Mar 2014 12:45:45 +0000 The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC). The tablets were prepared using microcrystalline cellulose (MCC) PH 102 as diluent along with crospovidone (CP), croscarmellose sodium (CCM), and sodium starch glycolate (SSG) as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT), and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results. M. M. Gupta, Niraj Gupta, Bhupendra S. Chauhan, and Shweta Pandey Copyright © 2014 M. M. Gupta et al. All rights reserved. Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy Thu, 27 Mar 2014 09:44:36 +0000 The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs) of Amlodipine Besylate (AMLO) to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC) and methyl cellulose (MC) along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30), and sodium lauryl sulphate (SLS) as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w) of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism. K. M. Maheswari, Pavan Kumar Devineni, Sravanthi Deekonda, Salma Shaik, Naga Pravallika Uppala, and Buchi N. Nalluri Copyright © 2014 K. M. Maheswari et al. All rights reserved. Serratiopeptidase Niosomal Gel with Potential in Topical Delivery Thu, 20 Mar 2014 11:26:32 +0000 The objective of present study was to develop nonionic surfactant vesicles of proteolytic enzyme serratiopeptidase (SRP) by adapting reverse phase evaporation (REV) technique and to evaluate the viability of SRP niosomal gel in treating the topical inflammation. The feasibility of SRP niosomes by REV method using Span 40 and cholesterol has been successfully demonstrated in this investigation. The entrapment efficiency was found to be influenced by the molar ratio of Span 40 : cholesterol and concentration of SRP in noisome. The developed niosomes were characterized for morphology, particle size, and in vitro release. Niosomal gel was prepared by dispersing xanthan gum into optimized batch of SRP niosomes. Ex vivo permeation and in vivo anti-inflammatory efficacy of gel formulation were evaluated topically. SRP niosomes obtained were round in nanosize range. At Span 40 : cholesterol molar ratio 1 : 1 entrapment efficiency was maximum, that is, 54.82% ± 2.08, and showed consistent release pattern. Furthermore ex vivo skin permeation revealed that there was fourfold increase in a steady state flux when SRP was formulated in niosomes and a significant increase in the permeation of SRP, from SRP niosomal gel containing permeation enhancer. In vivo efficacy studies indicated that SRP niosomal gel had a comparable topical anti-inflammatory activity to that of dicolfenac gel. Ujwala A. Shinde and Shivkumar S. Kanojiya Copyright © 2014 Ujwala A. Shinde and Shivkumar S. Kanojiya. All rights reserved. Development and Evaluation of Novel Self-Nanoemulsifying Drug Delivery Systems Based on a Homolipid from Capra hircus and Its Admixtures with Melon Oil for the Delivery of Indomethacin Thu, 20 Mar 2014 09:22:32 +0000 In this study, goat fat (Capra hircus) and melon oil were extracted and used to formulate self-nanoemulsifying drug delivery systems (SNEDDS) based on either goat fat alone or its admixture with melon oil by employing escalating ratios of oil(s), surfactant blend (1 : 1 Tween 60 and Tween 80), and cosurfactant (Span 85), with or without carbosil, a glidant, for the delivery of indomethacin. The formulations were encapsulated in hard gelatin capsules and then assessed using isotropicity test, aqueous dilution stability and precipitation propensity, absolute drug content, emulsification time, in vitro drug release, and anti-inflammatory activity. The SNEDDS exhibited low precipitation propensity and excellent stability on copious dilution, as well as high drug release in vitro and in vivo. The inhibition produced by the SNEDDS was comparable to that of indomethacin injection (positive control) for much of the 5 h test period, indicating a high degree of bioavailability of the administered SNEDDS. The absolute drug contents and emulsification times fell within narrow limits. This study has shown that a 1 : 1 ratio of melon oil and goat fat could confer favourable properties with respect to drug release and anti-inflammatory activity on SNEDDS for the delivery of indomethacin, thus encouraging further development of the formulations. Nicholas C. Obitte, Kenneth C. Ofokansi, and Franklin C. Kenechukwu Copyright © 2014 Nicholas C. Obitte et al. All rights reserved. Formulation and Characterization of Solid Dispersion Prepared by Hot Melt Mixing: A Fast Screening Approach for Polymer Selection Wed, 12 Mar 2014 11:41:45 +0000 Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymer-plasticizer-sulindac combinations. The sulindac-polymer-plasticizer combination that was stable with good film forming properties was processed by hot melt mixing, a technique close to hot melt extrusion, to predict its behavior in a hot melt extrusion process. Hot melt mixing is not a substitute to hot melt extrusion but is an aid in predicting the formation of molecularly dispersed form of a given set of drug-polymer-plasticizer combination in a hot melt extrusion process. The formulations were characterized by advanced techniques like optical microscopy, differential scanning calorimetry, hot stage microscopy, dynamic vapor sorption, and X-ray diffraction. Subsequently, the best drug-polymer-plasticizer combination obtained by hot melt mixing was subjected to hot melt extrusion process to validate the usefulness of hot melt mixing as a predictive tool in hot melt extrusion process. Arno A. Enose, Priya K. Dasan, H. Sivaramakrishnan, and Sanket M. Shah Copyright © 2014 Arno A. Enose et al. All rights reserved. Development and Validation of Liquid Chromatographic Method for Estimation of Naringin in Nanoformulation Thu, 06 Mar 2014 11:23:24 +0000 A simple, precise, accurate, rapid, and sensitive reverse phase high performance liquid chromatography (RP-HPLC) method with UV detection has been developed and validated for quantification of naringin (NAR) in novel pharmaceutical formulation. NAR is a polyphenolic flavonoid present in most of the citrus plants having variety of pharmacological activities. Method optimization was carried out by considering the various parameters such as effect of pH and column. The analyte was separated by employing a C18 ( mm, 5 μm) column at ambient temperature in isocratic conditions using phosphate buffer pH 3.5: acetonitrile (75 : 25% v/v) as mobile phase pumped at a flow rate of 1.0 mL/min. UV detection was carried out at 282 nm. The developed method was validated according to ICH guidelines Q2(R1). The method was found to be precise and accurate on statistical evaluation with a linearity range of 0.1 to 20.0 μg/mL for NAR. The intra- and interday precision studies showed good reproducibility with coefficients of variation (CV) less than 1.0%. The mean recovery of NAR was found to be 99.33 ± 0.16%. The proposed method was found to be highly accurate, sensitive, and robust. The proposed liquid chromatographic method was successfully employed for the routine analysis of said compound in developed novel nanopharmaceuticals. The presence of excipients did not show any interference on the determination of NAR, indicating method specificity. Kranti P. Musmade, M. Trilok, Swapnil J. Dengale, Krishnamurthy Bhat, M. S. Reddy, Prashant B. Musmade, and N. Udupa Copyright © 2014 Kranti P. Musmade et al. All rights reserved. A Critical Appraisal of Solubility Enhancement Techniques of Polyphenols Mon, 03 Mar 2014 10:58:59 +0000 Polyphenols constitute a family of natural substances distributed widely in plant kingdom. These are produced as secondary metabolites by plants and so far 8000 representatives of this family have been identified. Recently, there is an increased interest in the polyphenols because of the evidence of their role in prevention of degenerative diseases such as neurodegenerative diseases, cancer, and cardiovascular diseases. Although a large number of drugs are available in the market for treatment of these diseases, however, the emphasis these days is on the exploitation of natural principles derived from plants. Most polyphenols show low in vivo bioavailability thus limiting their application for oral drug delivery. This low bioavailability could be associated with low aqueous solubility, first pass effect, metabolism in GIT, or irreversible binding to cellular DNA and proteins. Therefore, there is a need to devise strategies to improve oral bioavailability of polyphenols. Various approaches like nanosizing, self-microemulsifying drug delivery systems (SMEDDS), microencapsulation, complexation, and solid dispersion can be used to increase the bioavailability. This paper will highlight the various methods that have been employed till date for the solubility enhancement of various polyphenols so that a suitable drug delivery system can be formulated. Harkiran Kaur and Gurpreet Kaur Copyright © 2014 Harkiran Kaur and Gurpreet Kaur. All rights reserved. Formulation Development and Evaluation of Fast Disintegrating Tablet of Cetirizine Hydrochloride: A Novel Drug Delivery for Pediatrics and Geriatrics Tue, 18 Feb 2014 12:19:55 +0000 Recent developments in fast disintegrating tablets have brought convenience in dosing to pediatric and elderly patients who have trouble in swallowing tablets. The objective of the present study was to prepare the fast disintegrating tablet of Cetirizine Hydrochloride for allergic and respiratory disorders. As precision of dosing and patient's compliance become important prerequisite for a long-term treatment, there is a need to develop a formulation for this drug which overcomes problems such as difficulty in swallowing, inconvenience in administration while travelling, and patient’s acceptability. Hence, the present investigation was undertaken with a view to develop a fast disintegrating tablet of Cetirizine Hydrochloride which offers a new range of products having desired characteristics and intended benefits. Superdisintegrants such as Sodium Starch Glycolate were optimized. Different binders were optimized along with optimized superdisintegrant concentration. The tablets were prepared by direct compression technique. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time and uniformity of content. Optimized formulation was evaluated by in vitro dissolution test, drug excipient compatibility and accelerated stability study. It was concluded that fast disintegrating tablets of Cetirizine Hydrochloride were formulated successfully with desired characteristics which disintegrated rapidly, provide rapid onset of action, and enhance the patient convenience and compliance. Deepak Sharma, Mankaran Singh, Dinesh Kumar, and Gurmeet Singh Copyright © 2014 Deepak Sharma et al. All rights reserved. The Population Pharmacokinetic Models of Tacrolimus in Chinese Adult Liver Transplantation Patients Thu, 13 Feb 2014 17:10:48 +0000 Aim. The aim of this study was to establish population pharmacokinetic models of tacrolimus in Chinese adult liver transplantation patients. Methods. Tacrolimus dose and concentration data were obtained from 47 Chinese adult liver transplant recipients, and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. Results. The structural model was a two-compartment model with first-order absorption. The typical population values of tacrolimus for the pharmacokinetic parameters of apparent clearance (), apparent distribution volume of the central compartment (), intercompartmental clearance (), apparent distribution volume of the peripheral compartment (), and absorption rate () were 11.2 L/h, 406 L, 57.3 L/h, 503 L, and 0.723 h−1, respectively. The interindividual variabilities of these parameters were 16.2%, 163%, 19.7%, 199%, and 74.3%, respectively, and the intraindividual variability of observed concentration was 26.54%. The covariates retained in the final models were postoperative days (POD) and dosage per day (DOSE) on . Conclusion. Population pharmacokinetic models of tacrolimus were developed in Chinese adult liver transplant patients. These results could provide the interpretation of the outcome of pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy. Liqin Zhu, Hao Wang, Xiaoye Sun, Wei Rao, Wei Qu, Yuan Zhang, and Liying Sun Copyright © 2014 Liqin Zhu et al. All rights reserved. Microbicides for the Treatment of Sexually Transmitted HIV Infections Wed, 12 Feb 2014 11:20:37 +0000 Approximately 34 million people were living with human immunodeficiency virus (HIV-1) at the end of 2011. From the last two decades, researchers are actively involved in the development of an effective HIV-1 treatment, but the results intended are still doubtful about the eradication of HIV. The HIV-1 virus has gone from being an “inherently untreatable” infectious agent to the one liable to be affected by a range of approved therapies. Candidate microbicides have been developed to target specific steps in the process of viral transmission. Microbicides are self-administered agents that can be applied to vaginal or rectal mucosal surfaces with the aim of preventing, or reducing, the transmission of sexually transmitted infections (STIs) including HIV-1. The development of efficient, widely available, and low-cost microbicides to prevent sexually transmitted HIV infections should be given high priority. In this review, we studied the various forms of microbicides, their mechanism of action, and their abundant approaches to control the transmission of sexually transmitted infections (STIs). Onkar Singh, Tarun Garg, Goutam Rath, and Amit K. Goyal Copyright © 2014 Onkar Singh et al. All rights reserved. Development and Evaluation of Taste Masked Granular Formulation of Satranidazole by Melt Granulation Technique Wed, 12 Feb 2014 08:48:56 +0000 Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and pediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets. Satranidazole is a new nitro-imidazole derivative with bitter taste and is available in market as film coated tablet. The purpose of this research was to mask the bitter taste of Satranidazole by coating complexation with low melting point wax and Eudragit EPO. Different types of wax (glyceryl monostearate, stearic acid and cetyl alcohol) were tried for taste masking. The drug to stearic acid ratio 1 : 2 was found to be optimum on the basis of taste evaluation and in vitro release. The formulated granules were found to possess good flow property. FTIR studies confirmed that there was no interaction between drug and excipients. Scanning Electron Microscopy of drug and the optimized batch of granules was performed. The in vitro release of drug from granules was compared with marketed tablet formulation. The taste masked granules of optimized batch showed 87.65% release of drug in 1 hr which is comparable to that of marketed tablet formulation. Harshal Ashok Pawar and Pooja Rasiklal Joshi Copyright © 2014 Harshal Ashok Pawar and Pooja Rasiklal Joshi. All rights reserved. Combinative Particle Size Reduction Technologies for the Production of Drug Nanocrystals Mon, 06 Jan 2014 12:33:04 +0000 Nanosizing is a suitable method to enhance the dissolution rate and therefore the bioavailability of poorly soluble drugs. The success of the particle size reduction processes depends on critical factors such as the employed technology, equipment, and drug physicochemical properties. High pressure homogenization and wet bead milling are standard comminution techniques that have been already employed to successfully formulate poorly soluble drugs and bring them to market. However, these techniques have limitations in their particle size reduction performance, such as long production times and the necessity of employing a micronized drug as the starting material. This review article discusses the development of combinative methods, such as the NANOEDGE, H 96, H 69, H 42, and CT technologies. These processes were developed to improve the particle size reduction effectiveness of the standard techniques. These novel technologies can combine bottom-up and/or top-down techniques in a two-step process. The combinative processes lead in general to improved particle size reduction effectiveness. Faster production of drug nanocrystals and smaller final mean particle sizes are among the main advantages. The combinative particle size reduction technologies are very useful formulation tools, and they will continue acquiring importance for the production of drug nanocrystals. Jaime Salazar, Rainer H. Müller, and Jan P. Möschwitzer Copyright © 2014 Jaime Salazar et al. All rights reserved. Transdermal Delivery of Small Interfering RNA with Elastic Cationic Liposomes in Mice Thu, 26 Dec 2013 14:04:46 +0000 We developed elastic cationic liposomal vectors for transdermal siRNA delivery. These liposomes were prepared with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid and sodium cholate (NaChol) or Tween 80 as an edge activator. When NaChol or Tween 80 was included at 5, 10, and 15% (w/w) into DOTAP liposomal formulations (C5-, C10-, and C15-liposomes and T5-, T10-, and T15-liposomes), C15- and T10-liposomes showed 2.4- and 2.7-fold-higher elasticities than DOTAP liposome, respectively. Although the sizes of all elastic liposomes prepared in this study were about 80–90 nm, the sizes of C5-, C10- and C15-liposome/siRNA complexes (lipoplexes) were about 1,700–1,800 nm, and those of T5-, T10-, and T15-lipoplexes were about 550–780 nm. Their elastic lipoplexes showed strong gene suppression by siRNA without cytotoxicity when transfected into human cervical carcinoma SiHa cells. Following skin application of the fluorescence-labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution. These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally. Yoshiyuki Hattori, Masataka Date, Shohei Arai, Kumi Kawano, Etsuo Yonemochi, and Yoshie Maitani Copyright © 2013 Yoshiyuki Hattori et al. All rights reserved. Isolation and Evaluation of Mucilage of Adansonia digitata Linn as a Suspending Agent Tue, 24 Dec 2013 15:06:44 +0000 Natural excipients can serve as alternative to synthetic products because of local accessibility, biodegradability, eco-friendly nature and cost effectiveness as compared to synthetic products. Therefore, it is a current need to explore natural excipients that can be used as an effective alternative excipient for the formulation of pharmaceutical dosage forms. Adansonia digitata (Malvaceae) has been traditionally used as febrifuge, antiasthmatic and also in the treatment of dysentery, smallpox, and measles. Reports have indicated that mucilage of the leaves of the plant is edible and nontoxic; hence, the present study is an attempt of isolation and evaluation of mucilage obtained from leaves of Adansonia digitata as suspending agent. Various physicochemical as well as suspending agent properties of mucilage were studied. Mucilage obtained from leaves has shown comparable results with sodium carboxy methyl cellulose. S. S. Deshmukh, Y. S. Katare, S. S. Shyale, S. S. Bhujbal, S. D. Kadam, D. A. Landge, D. V. Shah, and J. B. Pawar Copyright © 2013 S. S. Deshmukh et al. All rights reserved. Development of Orodispersible Tablets of Candesartan Cilexetil-β-cyclodextrin Complex Tue, 24 Sep 2013 15:18:04 +0000 The aim of this study was to investigate the use of inclusion complexation technique employing β-cyclodextrin in improving the dissolution profile of candesartan cilexetil, a BCS class-II drug, and to formulate the inclusion complex into orodispersible tablets. The inclusion complexes were formed by physical mixing, kneading, coevaporation, and lyophilisation methods. Inclusion complexes were characterized by FTIR, DSC, XRD, NMR, and mass spectral studies. Inclusion complexes prepared using kneading, and lyophilisation techniques in the molar ratio 1 : 5 with β-cyclodextrin were used for formulating orodispersible tablets by direct compression with different superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, and low substituted hydroxypropyl cellulose in varying concentrations. The directly compressible powder was evaluated for precompression parameters, and the prepared orodispersible tablets were evaluated for postcompression parameters. Drug-excipient compatibility studies showed no interaction, and characterization proved the formation of inclusion complex. In vitro disintegration time was found to be within 3 minutes, and all the formulations showed complete drug release of 100% within 20 minutes. The optimized formulation was found to be stable after 6 months and showed no significant change in drug content. This work proved β-cyclodextrins to be effective solubilizing agent in improving the solubility of poorly water soluble drugs. Maddukuri Sravya, Rajamanickam Deveswaran, Srinivasan Bharath, Basappa Veerbadraiah Basavaraj, and Varadharajan Madhavan Copyright © 2013 Maddukuri Sravya et al. All rights reserved. Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles Thu, 12 Sep 2013 10:11:47 +0000 Neurodegeneration is characterized by progressive loss of structure and function of neurons. Several therapeutic methods and drugs are available to alleviate the symptoms of these diseases. The currently used delivery strategies such as implantation of catheters, intracarotid infusions, surgeries, and chemotherapies are invasive in nature and pose a greater risk of postsurgical complications, which can have fatal side effects. The current study utilizes a peptide (TAT and MGF) tagged PEGylated chitosan nanoparticle formulation for siRNA delivery, administered intranasally, which can bypass the blood brain barrier. The study investigates the optimal dose, duration, biodistribution, and toxicity, of the nanoparticle-siRNA formulation, in-vivo. The results indicate that 0.5 mg/kg of siRNA is delivered successfully to the hippocampus, thalamus, hypothalamus, and Purkinje cells in the cerebellum after 4 hrs of post intranasal delivery. The results indicate maximum delivery to the brain in comparison to other tissues with no cellular toxic effects. This study shows the potential of peptide-tagged PEGylated chitosan nanoparticles to be delivered intranasally and target brain tissue for the treatment of neurological disorders. Meenakshi Malhotra, Catherine Tomaro-Duchesneau, Shyamali Saha, and Satya Prakash Copyright © 2013 Meenakshi Malhotra et al. All rights reserved. Preparation, Characterization, and In Vivo Evaluation of Olanzapine Poly(D,L-lactide-co-glycolide) Microspheres Mon, 12 Aug 2013 17:18:59 +0000 The aim of this study was to prepare injectable depot formulations of Olanzapine using four poly(D,L-lactide-co-glycolide) (PLGA) polymers of varying molecular weight and copolymer composition, and evaluate in vivo performance in rats. In vivo release profiles from the formulations were governed chiefly by polymer molecular weight and to a lesser extent, copolymer composition. Formulations A and B, manufactured using low molecular weight PLGA and administered at 10 mg/kg dose, released drug within 15 days. Formulation C, prepared from intermediate molecular weight PLGA and administered at 20 mg/kg dose, released drug in 30 days, while Formulation D, manufactured using a high molecular weight polymer and administered at 20 mg/kg dose, released drug in 45 days. A simulation of multiple dosing at 7- and 10-day intervals for Formulations A and B revealed that steady state was achieved within 7–21 days and 10–30 days, respectively. Similarly, simulations at 15-day intervals for Formulations C and D indicated that steady state levels were reached during days 15–45. Overall, steady state levels for 7-, 10-, or 15-day dosing ranged between 45 and 65 ng/mL for all the formulations, implying that Olanzapine PLGA microspheres can be tailored to treat patients with varying clinical needs. Susan D’Souza, Jabar A. Faraj, Stefano Giovagnoli, and Patrick P. DeLuca Copyright © 2013 Susan D’Souza et al. All rights reserved. Quantum Dot-Loaded Liposomes to Evaluate the Behavior of Drug Carriers after Oral Administration Thu, 18 Jul 2013 12:34:08 +0000 We have developed submicron-sized liposomes modified with a mucoadhesive polymer to enhance peptide drug absorption after oral administration. Liposomal behavior in the gastrointestinal tract is a critical factor for effective peptide drug delivery. The purpose of this study was to prepare quantum dot- (QD-) loaded submicron-sized liposomes and examine liposomal behavior in the body after oral administration using in vivo fluorescence imaging. Two types of CdSe/CdZnS QDs with different surface properties were used: hydrophobic (unmodified) QDs and hydrophilic QDs with glutathione (GSH) surface modifications. QD- and GSH-QD-loaded liposomes were prepared by a thin film hydration method. Transmission electron microscopy revealed that QDs were embedded in the liposomal lipid bilayer. Conversely, GSH-QDs were present in the inner aqueous phase. Some of the GSH-QDs were electrostatically associated with the lipid membrane of stearylamine-bearing cationic liposomes. QD-loaded liposomes were detected in Caco-2 cells after exposure to the liposomes, and these liposomes were not toxic to the Caco-2 cells. Furthermore, we evaluated the in vivo bioadhesion and intestinal penetration of orally administered QD-loaded liposomes by observing the intestinal segment using confocal laser scanning microscopy. Kohei Tahara, Shiho Fujimoto, Fumihiko Fujii, Yuichi Tozuka, Takashi Jin, and Hirofumi Takeuchi Copyright © 2013 Kohei Tahara et al. All rights reserved. Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells Sun, 23 Jun 2013 13:18:24 +0000 Traditional anticancer chemotherapy often displays toxic side effects, poor bioavailability, and a low therapeutic index. Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index. Here we report a polymersome-based system to deliver gemcitabine to Panc-1 cells in vitro. The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL. We showed that we can encapsulate gemcitabine within stable 200 nm vesicles with a 10% loading efficiency. These vesicles displayed a controlled release of gemcitabine with 60% release after 2 days at physiological pH. Upon treatment of Panc-1 cells in vitro, vesicles were internalized as verified with fluorescently labeled polymersomes. Clonogenic assays to determine cell survival were performed by treating Panc-1 cells with varying concentrations of unencapsulated gemcitabine (FreeGem) and polymersome-encapsulated gemcitabine (PolyGem) for 48 hours. 1 μM PolyGem was equivalent in tumor cell toxicity to 1 μM FreeGem, with a one log cell kill observed. These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer. Nimil Sood, Walter T. Jenkins, Xiang-Yang Yang, Nikesh N. Shah, Joshua S. Katz, Cameron J. Koch, Paul R. Frail, Michael J. Therien, Daniel A. Hammer, and Sydney M. Evans Copyright © 2013 Nimil Sood et al. All rights reserved. Self-Microemulsifying Drug Delivery System: Formulation and Study Intestinal Permeability of Ibuprofen in Rats Mon, 10 Jun 2013 16:29:48 +0000 The study was aimed at developing a self-microemulsifying drug delivery system (SMEDDS) of Ibuprofen for investigating its intestinal transport behavior using the single-pass intestinal perfusion (SPIP) method in rat. Methods. Ibuprofen loaded SMEDDS (ISMEDDS) was developed and was characterized. The permeability behavior of Ibuprofen over three different concentrations (20, 30, and 40 µg/mL) was studied in each isolated region of rat intestine by SPIP method at a flow rate of 0.2 mL/min. The human intestinal permeability was predicted using the Lawrence compartment absorption and transit (CAT) model since effective permeability coefficients () values for rat are highly correlated with those of human, and comparative intestinal permeability of Ibuprofen was carried out with plain drug suspension (PDS) and marketed formulation (MF). Results. The developed ISMEDDS was stable, emulsified upon mild agitation with 44.4 nm ± 2.13 and 98.86% ± 1.21 as globule size and drug content, respectively. Higher in colon with no significant difference in jejunum, duodenum, and ileum was observed. The estimated human absorption of Ibuprofen for the SMEDDS was higher than that for PDS and MF . Conclusion. Developed ISMEDDS would possibly be advantageous in terms of minimized side effect, increased bioavailability, and hence the patient compliance. Bharat Bhushan Subudhi and Surjyanarayan Mandal Copyright © 2013 Bharat Bhushan Subudhi and Surjyanarayan Mandal. All rights reserved. Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability Mon, 03 Jun 2013 15:25:18 +0000 Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9%) due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN). Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC). Stable quetiapine fumarate SLNs having a mean particle size of 200–250 nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2 months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism. Arjun Narala and Kishan Veerabrahma Copyright © 2013 Arjun Narala and Kishan Veerabrahma. All rights reserved. Pentoxifylline Loaded Floating Microballoons: Design, Development and Characterization Thu, 09 May 2013 14:22:05 +0000 The floating microballoons have been utilized to obtain prolonged and uniform release in the stomach. The objective of the present study involves design, development, and characterization of pentoxifylline loaded floating microballoons to prolong their gastric residence time. Pentoxifylline (trisubstituted xanthine derivative) loaded microballoons were prepared by the solvent evaporation technique using different concentrations of polymers like HPMC K4M and ethyl cellulose (EC) in ethyl alcohol and dichloromethane organic solvent system. Microballoons were characterized for their particle size, surface morphology, production yield, loading efficiency, buoyancy percentage, and in vitro drug release studies. From the characterization it was observed that increases in amount of polymers (HPMC K4M and EC) led to increased particle size, loading efficiency, and buoyancy percentage, and retarded drug release. The particle size, particle yield, loading efficiency, buoyancy percentage and in vitro drug release for optimized formulation (F3) were found to be  µm, %, %, %, and %, respectively. The data was fitted to different kinetic models to illustrate its anomalous (non-Fickian) diffusion. The in vitro result showed that formulations comprised of varying concentrations of ethyl cellulose in higher proportion exhibited much retarded drug release as compared to formulations comprised of higher proportion of varying concentrations of HPMC K4M. Prashant Malik, Upendra Nagaich, Raj Kaur Malik, and Neha Gulati Copyright © 2013 Prashant Malik et al. All rights reserved. Antibacterial Derivatives of Ciprofloxacin to Inhibit Growth of Necrotizing Fasciitis Associated Penicillin Resistant Escherichia coli Thu, 02 May 2013 11:29:44 +0000 Escherichia coli (E. coli) is associated with necrotizing fasciitis (type I) and can induce enough damage to tissue causing hypoxia. Three ester derivatives of the broad-spectrum antibiotic ciprofloxacin were placed into bacteria culture simultaneously with the parent ciprofloxacin (drug 1) to ascertain the level of antibacterial activity. The n-propyl (drug 2), n-pentyl (drug 3), and n-octyl (drug 4) esters of ciprofloxacin were synthesized under mixed phase conditions and by microwave excitation. The formation of ester derivatives of ciprofloxacin modified important molecular properties such as Log P and polar surface area which improves tissue penetration, yet preserved strong antibacterial activity. The Log P values for drugs 1, 2, 3, and 4 became −0.701, 0.437, 1.50, and 3.02, respectively. The polar surface areas for drugs 1, 2, 3, and 4 were determined to be 74.6 Angstroms2, 63.6 Angstroms2, 63.6 Angstroms2, and 63.6 Angstroms2, respectively. These values of Log P and polar surface area improved tissue penetration, as indicated by the determination of dermal permeability coefficient () and subsequently into the superficial fascial layer. All drugs induced greater than 60% bacterial cell death at concentrations less than 1.0 micrograms/milliliter. The ester derivatives of ciprofloxacin showed strong antibacterial activity toward penicillin resistant E. coli. Ronald Bartzatt, Suat L. G. Cirillo, and Jeffrey D. Cirillo Copyright © 2013 Ronald Bartzatt et al. All rights reserved. Cellular Redox Status Regulates Emodin-Induced Radiosensitization of Nasopharyngeal Carcinoma Cells In Vitro and In Vivo Tue, 16 Apr 2013 15:41:03 +0000 Here, we report that regulation of cellular redox status is required for radiosensitization of nasopharyngeal carcinoma (NPC) cells by emodin. We evaluated emodin’s radiosensitivity-enhancing ability by using NPC cells in vitro and xenografts in vivo. A clonogenic assay was performed to evaluate NPC cell survival and to determine dose modification factors. Flow cytometry, western blot analysis, and in vivo radiation-induced tumor regrowth delay assays were performed to characterize emodin’s effects. Exposure of CNE-1 NPC cells to emodin enhanced their radiosensitivity. HIF-1 expression significantly increased under hypoxic conditions but did not change after treatment with emodin alone. Emodin downregulated mRNA and protein expression of HIF-1. Cells exposed to radiation and emodin underwent significant cell cycle arrest at the G2/M phase. The percentage of apoptotic cells and reactive oxygen species (ROS) levels were significantly higher in the group exposed to emodin and radiation hypoxic group than in the other groups. Compared to the CNE-1 xenografts exposed to radiation alone, CNE-1 xenografts exposed to radiation with emodin showed significantly enhanced radiation effects. Our data suggest that emodin effectively enhanced the radiosensitivity of CNE-1 cells in vitro and in vivo. The mechanism appears to involve ROS generation and ROS-mediated inhibition of HIF-1 expression. Huaxin Hou, Danrong Li, Daohai Cheng, Li Li, Ying Liu, and Yi Zhou Copyright © 2013 Huaxin Hou et al. All rights reserved. Determination of Zalcitabine in Medicaments by Differential Pulse Voltammetry Thu, 04 Apr 2013 18:26:25 +0000 The zalcitabine (ddC) has been extensively used in the treatment of HIV patients due to its antiretroviral activity. The quality control of this active principle in medications is of outstanding importance to public health. The principal objective of the current study was the development of an alternative analytical methodology for the zalcitabine determination using a voltammetric process. The zalcitabine gives a reduction peak (at  V versus Ag/AgCl) at the hanging mercury drop electrode (HMDE). The differential pulse voltammetric response is evaluated with respect to the scan rate (20 mV/s), pulse amplitude (50 mV), support electrolyte (Clark-Lubs buffer), pH (2.0), and other variables. The response is linear over the 10.0 to 28.0 mg/L (47 to 133 μM) concentration range, and the detection limit is 2.08 mg/L. The validation of this method was realized using a governmental Brazilian document (Inmetro, 2007) and the results are reported for medication drugs. Katia Christina Leandro, Josino Costa Moreira, and Pércio Augusto Mardini Farias Copyright © 2013 Katia Christina Leandro et al. All rights reserved. Plantago ovata F. Mucilage-Alginate Mucoadhesive Beads for Controlled Release of Glibenclamide: Development, Optimization, and In Vitro-In Vivo Evaluation Thu, 04 Apr 2013 16:11:31 +0000 The current study deals with the development and optimization of ispaghula (Plantago ovata F.) husk mucilage- (IHM-) alginate mucoadhesive beads containing glibenclamide by ionotropic gelation technique. The effects of sodium alginate (SA) to IHM and cross-linker (CaCl2) concentration on the drug encapsulation efficiency (DEE, %), as well as cumulative drug release after 10 hours (, %), were optimized using 32 factorial design based on response surface methodology. The observed responses were coincided well with the predicted values by the experimental design. The optimized mucoadhesive beads exhibited % w/w of DEE and good mucoadhesivity with the biological membrane in wash-off test and sustained drug release profile over 10 hours. The beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads was followed by controlled release (zero-order) pattern with super case-II transport mechanism. The optimized glibenclamide-loaded IHM-alginate mucoadhesive beads showed significant antidiabetic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Amit Kumar Nayak, Dilipkumar Pal, and Kousik Santra Copyright © 2013 Amit Kumar Nayak et al. All rights reserved. Artemether-Soluplus Hot-Melt Extrudate Solid Dispersion Systems for Solubility and Dissolution Rate Enhancement with Amorphous State Characteristics Thu, 04 Apr 2013 11:12:21 +0000 This work studied artemether (ARTM) solid dispersion (SD) formulation using mixture of polymer excipient Soluplus, PEG 400, Lutrol F127, and Lutrol F68 melts at temperatures lower than the melting point of ARTM using a laboratory-size, single-screw rotating batch extruder. The effects of three surfactants PEG 400, Lutrol F127, and Lutrol F68 and parameters like mixing temperature, screw rotating speed, and residence time were systematically studied. SEM, XRD, and FT-IR were employed to investigate the evolution of ARTM’s dissolution into the molten excipient. Differential scanning calorimetry (DSC) was used to quantitatively study the melting enthalpy evolution of the drug. The results showed that the dissolution rate increased with increasing the ratio of polymer and surfactant to that of drug. It was concluded that the dissolution of the drug in the polymer melt is a convective diffusion process and that laminar distributive mixing can significantly enhance the dissolution rate. The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced. In vitro antimalarial studies revealed marked improvement in IC50 values. Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of ARTM. Ritesh A. Fule, Tarique S. Meer, Ajay R. Sav, and Purnima D. Amin Copyright © 2013 Ritesh A. Fule et al. All rights reserved.