http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Thu, 09 May 2013 14:22:05 +0000 http://www.hindawi.com/journals/jph/2013/107291/ 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. Thu, 02 May 2013 11:29:44 +0000 http://www.hindawi.com/journals/jph/2013/517638/ 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. Tue, 16 Apr 2013 15:41:03 +0000 http://www.hindawi.com/journals/jph/2013/218297/ 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. Thu, 04 Apr 2013 18:26:25 +0000 http://www.hindawi.com/journals/jph/2013/495814/ 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. Thu, 04 Apr 2013 16:11:31 +0000 http://www.hindawi.com/journals/jph/2013/151035/ 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. Thu, 04 Apr 2013 11:12:21 +0000 http://www.hindawi.com/journals/jph/2013/151432/ 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. Thu, 28 Mar 2013 17:59:27 +0000 http://www.hindawi.com/journals/jph/2013/678132/ In the present investigation, mixed-solvency approach has been applied for the enhancement of aqueous solubility of a poorly water- soluble drug, zaltoprofen (selected as a model drug), by making blends (keeping total concentrations 40% w/v, constant) of selected water-soluble substances from among the hydrotropes (urea, sodium benzoate, sodium citrate, nicotinamide); water-soluble solids (PEG-4000, PEG-6000); and co-solvents (propylene glycol, glycerine, PEG-200, PEG-400, PEG-600). Aqueous solubility of drug in case of selected blends (12 blends) ranged from 9.091 ± 0.011 mg/ml–43.055 ± 0.14 mg/ml (as compared to the solubility in distilled water 0.072 ± 0.012 mg/ml). The enhancement in the solubility of drug in a mixed solvent containing 10% sodium citrate, 5% sodium benzoate and 25 % S cosolvent (25% S cosolvent contains PEG200, PEG 400, PEG600, Glycerine and Propylene glycol) was more than 600 fold. This proved a synergistic enhancement in solubility of a poorly water-soluble drug due to mixed cosolvent effect. Each solubilized product was characterized by ultraviolet and infrared techniques. Various properties of solution such as pH, viscosity, specific gravity and surface tension were studied. The developed formulation was studied for physical and chemical stability. This mixed solvency shall prove definitely a boon for pharmaceutical industries for the development of dosage form of poorly water soluble drugs. Shailendra Singh Solanki, Love Kumar Soni, and Rajesh Kumar Maheshwari Copyright © 2013 Shailendra Singh Solanki et al. All rights reserved. Mon, 11 Mar 2013 09:07:38 +0000 http://www.hindawi.com/journals/jph/2013/270472/ Extraction procedure was standardized and for the soluble, glycoside, and wall-bound fractions of phenolic acids from Vetiveria zizanioides. The water soluble alkaline extract which represents the cell wall-bound fraction contained the highest amount of phenolic acids (2.62 ± 1.2 μM/g fwt GA equivalents). Increased phenolic content in the cell wall indicates more lignin deposition which has an important role in plant defense and stress mitigation. Antioxidant property expressed as percentage TEAC value obtained by ABTS assay was correlated with the amount of phenolic acids and showed a Pearson's coefficient 0.988 (significant at 0.01 level). The compounds p-coumaric acid, p-dihydroxybenzoic acid, and ferulic acid were detected in the acidic extracts by HPLC analysis. The plant extracts exhibited considerable antimicrobial activity against tested bacterial and fungal strains. Jha Prajna, Jindal Richa, and Chakraborty Dipjyoti Copyright © 2013 Jha Prajna et al. All rights reserved. Thu, 28 Feb 2013 14:58:37 +0000 http://www.hindawi.com/journals/jph/2013/390425/ Buckysomes, liposome-like vesicles comprised of dendritic C60 subunits that self-assemble into unilamellar vesicles, are unique nanovectors that have utility in drug delivery. We have prepared paclitaxel-embedded buckysomes (PEBs) and examined biodistriubition profiles with commercially available formulations of the drug. As compared to Abraxane, an albumin-bound formulation of paclitaxel, PEBs showed higher tissue accumulation in the liver and the kidney at 45 and 60 minutes and in the lungs at 30 minutes, making them suitable drug-delivery carriers for short-term therapy to the mentioned organs. These buckysomes can be further functionalized to specifically deliver paclitaxel to the tumor site. Delia Danila, Eva Golunski, Ranga Partha, Madonna McManus, Tina Little, and Jodie Conyers Copyright © 2013 Delia Danila et al. All rights reserved. Wed, 27 Feb 2013 16:28:47 +0000 http://www.hindawi.com/journals/jph/2013/315902/ In present investigation liquisolid compact technique is investigated as a tool for enhanced dissolution of poorly water-soluble drug Rosuvastatin calcium (RVT). The model drug RVT, a HMG-Co A reductase inhibitor was formulated in form of directly compressed tablets and liquisolid compacts; and studied for in-vitro release characteristics at different dissolution conditions. In this technique, liquid medications of water insoluble drugs in non-volatile liquid vehicles can be converted into acceptably flowing and compressible powders. Formulated systems were assessed for precompression parameters like flow properties of liquisolid system, Fourior transform infra red spectra (FTIR) analysis, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and post compression parameters like content uniformity, weight variation, hardness and friability, disintegration test, wetting time, in vitro dissolution studies, effect of dissolution volume on drug release rate, and estimation of fraction of molecularly dispersed drug in liquid medication. As liquisolid compacts demonstrated significantly higher drug release rates, we lead to conclusion that it could be a promising strategy in improving the dissolution of poor water soluble drugs and formulating immediate release solid dosage forms. V. J. Kapure, V. V. Pande, and P. K. Deshmukh Copyright © 2013 V. J. Kapure et al. All rights reserved. Sun, 24 Feb 2013 08:55:15 +0000 http://www.hindawi.com/journals/jph/2013/417682/ A sensitive and precise RP-HPLC method has been developed for the simultaneous estimation of clidinium bromide (CDB) and chlordiazepoxide (CDZ) in pure and pharmaceutical formulations. The separation was achieved on a Nucleodur C8 ( mm i.d., 5 μm particle size) column at 25°C. CH3CN-MeOH-NH4OAc 0.1M (30 : 40 : 30, v/v/v) was used as the mobile phase at a flow rate of 1.0 mL min−1 and detector wavelength at 218 nm. Almotriptan (ALT) was used as internal standard. The validation of the proposed method was carried out for linearity, accuracy, precision, LOD, LOQ, and robustness. The method showed good linearity in the ranges of 2.5–300.0 and 3.0–500.0 μg mL−1 for CDB and CDZ, respectively. The percentage recovery obtained for CDB and CDZ was 100.40–103.38 and 99.98–105.59%, respectively. LOD and LOQ were 0.088 and 0.294 μg mL−1 for CDB and 0.121 and 0.403 μg mL−1 for CDZ, respectively. The proposed method was successfully applied to the determination of CDB and CDZ in combined dosage forms and the results tallied well with the label claim. Safwan Ashour and Nuha Kattan Copyright © 2013 Safwan Ashour and Nuha Kattan. All rights reserved. Thu, 21 Feb 2013 14:10:08 +0000 http://www.hindawi.com/journals/jph/2013/875906/ Although atomic force microscopy (AFM) has been used extensively to characterize cell membrane structure and cellular processes such as endocytosis and exocytosis, the corrugated surface of the cell membrane hinders the visualization of extracellular entities, such as liposomes, that may interact with the cell. To overcome this barrier, we used 90 nm nanogold particles to label FITC liposomes and monitor their endocytosis on human coronary artery endothelial cells (HCAECs) in vitro. We were able to study the internalization process of gold-coupled liposomes on endothelial cells, by using AFM. We found that the gold-liposomes attached to the HCAEC cell membrane during the first 15–30 min of incubation, liposome cell internalization occurred from 30 to 60 min, and most of the gold-labeled liposomes had invaginated after 2 hr of incubation. Liposomal uptake took place most commonly at the periphery of the nuclear zone. Dynasore monohydrate, an inhibitor of endocytosis, obstructed the internalization of the gold-liposomes. This study showed the versatility of the AFM technique, combined with fluorescent microscopy, for investigating liposome uptake by endothelial cells. The 90 nm colloidal gold nanoparticles proved to be a noninvasive contrast agent that efficiently improves AFM imaging during the investigation of biological nanoprocesses. Ana-María Zaske, Delia Danila, Michael C. Queen, Eva Golunski, and Jodie L. Conyers Copyright © 2013 Ana-María Zaske et al. All rights reserved. Thu, 21 Feb 2013 11:41:33 +0000 http://www.hindawi.com/journals/jph/2013/791370/ Hydrotropy is a phenomenon where the presence of a large quantity of one solute enhances the solubility of another solute. The mechanism of this phenomenon remains a topic of debate. This study employed molecular dynamics simulation to investigate the hydrotropic mechanism of a series of urea derivatives, that is, urea (UR), methylurea (MU), ethylurea (EU), and butylurea (BU). A poorly water-soluble compound, nifedipine (NF), was used as the model solute that was solubilized. Structural, dynamic, and energetic changes upon equilibration were analyzed to supply insights to the solubilization mechanism. The study demonstrated that NF and urea derivatives underwent significant nonstoichiometric molecular aggregation in the aqueous solution, a result consistent with the self-aggregation of urea derivatives under the same conditions. The analysis of hydrogen bonding and energy changes revealed that the aggregation was driven by the partial restoration of normal water structure. The energetic data also suggested that the promoted solubilization of NF is favored in the presence of urea derivatives. While the solutes aggregated to a varying degree, the systems were still in single-phase liquid state as attested by their active dynamics. Yong Cui Copyright © 2013 Yong Cui. All rights reserved. Tue, 29 Jan 2013 14:00:21 +0000 http://www.hindawi.com/journals/jph/2013/527380/ The objective of the present work was to enhance the solubility and dissolution of practically water-insoluble drug raloxifene HCl (RLX), for the same two approaches that were used. In the first approach, drug was kneaded with hydroxypropyl-β-cyclodextrin (HPβCD), and in the second one drug was cogrinded with modified guar gum (MGG). The drug-cyclodextrin complex and drug-MGG cogrind mixtures were characterized by differential scanning calorimetry, X-ray diffraction studies, scanning electron microscopy, and Fourier transform infrared spectroscopy. The solubility and dissolution study reveals that solubility and dissolution rate of RLX remarkably increased in both methods. It was concluded that the prepared inclusion complex showed a remarkable increase in solubility and dissolution of poorly water-soluble drug raloxifene. In the cogrinding mixture, a natural modified gum is used as a surfactant and enhances the solubility and dissolution of RLX without requiring addition of organic solvent or high temperature for its preparation; thus, process is less cumbersome and cost effective. But when both methods were compared; HPβCD complexation method showed significant enhancement of drug solubility. Payal H. Patil, Veena S. Belgamwar, Pratibha R. Patil, and Sanjay J. Surana Copyright © 2013 Payal H. Patil et al. All rights reserved. Sun, 20 Jan 2013 07:26:21 +0000 http://www.hindawi.com/journals/jph/2013/386546/ Bladder pain is a characteristic disorder of interstitial cystitis. Diazepam is well known for its antispasmodic activity in the treatment of muscular hypertonus. The aim of this work was to develop and characterize vaginal pessaries as an intravaginal delivery system of diazepam for the treatment of interstitial cystitis. In particular, the performance of two types of formulations, with and without beta-glucan, was compared. In particular, the preparation of pessaries, according to the modified Pharmacopeia protocol, the setup of the analytical method to determine diazepam, pH evaluation, dissolution profile, and photostability assay were reported. Results showed that the modified protocol permitted obtaining optimal vaginal pessaries, without air bubbles, with good consistency and handling and with good pH profiles. In order to determine the diazepam amount, calibration curves with good correlation coefficients were obtained, by the spectrophotometric method, using placebo pessaries as matrix with the addition of diazepam standard solution. This method was demonstrated sensible and accurate to determine the amount of drug in batches. Dissolution profiles showed a complete diazepam release just after 15 minutes, even if beta-glucan pessaries released drug more gradually. Finally, a possible drug photodegradation after exacerbated UV-visible exposition was evaluated. P. Capra, P. Perugini, M. Bleve, P. Pavanetto, G. Musitelli, B. Rovereto, and D. Porru Copyright © 2013 P. Capra et al. All rights reserved. Thu, 17 Jan 2013 15:54:48 +0000 http://www.hindawi.com/journals/jph/2013/907525/ A series of 3-[-(Substitutedbenzylideneamino)phenyl]-2-methyl-6-substituted quinazolin-4-ones (5–10), 3-[-(-chloro--oxo--substitutedphenylazetidin--yl)phenyl]-2-methyl-6-substitutedquinazolin-4-ones (11–16), and 3-[-(-substitutedphenyl--oxo-,-thiazolidin--yl)phentl]-2-methyl-6-substitutedquinazolin-4-ones (17–22) have been synthesized in the present study. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, NMR, and mass spectral data. All the newly synthesized compounds were screened for anti-inflammatory and analgesic activities. Chatrasal Singh Rajput and Shiwani Singhal Copyright © 2013 Chatrasal Singh Rajput and Shiwani Singhal. All rights reserved. Thu, 17 Jan 2013 15:32:26 +0000 http://www.hindawi.com/journals/jph/2013/418346/ The present investigation includes the preparation of liquid filling formulations for soft gels using an antihypertensive drug, valsartan (VAL), in order to improve its dissolution properties and thereby its bioavailability. Formulations were prepared using excipients like polyethylene glycol 400 (PEG 400), propylene glycol (PG), polyvinylpyrrolidone (PVP K-30), antioxidants, ethanol, and purified water. Prepared formulations were evaluated for appearance, pH, drug content percentage, viscosity, stability, and in vitro dissolution studies. The compatibility between the drug and excipients in formulations was confirmed by FTIR spectra. The drug contents were in the range of 99.62-99.63 and the viscosity was in the range of 60.9–591.7 cps with all the formulations developed. Formulations containing 10 mg PVP K 30 gave better dissolution properties when compared to formulations without PVP K 30, and a complete drug dissolution was observed within 10 min and followed the first-order release kinetics. Stability studies were conducted for selected formulations (F4–F9) for a period of 6 months at room temperature (~30°C/65% RH). From the studies, it can be concluded that VAL liquid filling formulations for soft gels were successfully prepared with in vitro dissolution properties superior when compared to VAL itself. Jyothi Sanaboina, K. M. Maheswari, Seetha Sunkara, Sravanthi Deekonda, and Buchi N. Nalluri Copyright © 2013 Jyothi Sanaboina et al. All rights reserved. Tue, 08 Jan 2013 18:10:00 +0000 http://www.hindawi.com/journals/jph/2013/501082/ The purpose of the present study was to develop and optimize the emulgel system for MTZ (Metronidazole), a poorly water soluble drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of Capmul 908 P, Acconon MC8-2, and propylene glycol. The emulgel was optimized using a three-factor, two-level factorial design, the independent variables selected were Capmul 908 P, and surfactant mixture (Acconon MC8-2 and gelling agent), and the dependent variables (responses) were a cumulative amount of drug permeated across the dialysis membrane in 24 h () and spreadability (). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses and . The statistical validity of the polynomials was established, and optimized formulation factors were selected. Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology. Emulgel system of MTZ was developed and optimized using 23 factorial design and could provide an effective treatment against topical infections. Monica Rao, Girish Sukre, Sheetal Aghav, and Manmeet Kumar Copyright © 2013 Monica Rao et al. All rights reserved. Thu, 27 Dec 2012 15:17:44 +0000 http://www.hindawi.com/journals/jph/2013/571464/ The investigation of ultradiluted (homeopathic) drugs is extremely interesting and challenging, and from that point of view this study shows novelty. A study of in vivo changes in heart rate of the Indian Bufo melanostictus caused by commercially available serially ultra-diluted and agitated extract of Digitalis purpurea has been tried in order to understand their pharmacological role. RR interval (of ECG) was compared after intraperitoneal administration of serially diluted and agitated Digitalis purpurea extract, diluent rectified spirit, and Digoxin in anesthetized animals. The study revealed statistically significant changes in the heart rate after application of these drugs except in case of Digoxin and the 200th serial dilution of Digitalis purpurea. The duration of RR intervals after application of the drugs was corroborative of the effect of Digoxin and Digitalis purpurea extract up to 30th dilution. Emission spectra were obtained for the experimental ultra-diluted Digitalis purpurea extract and Digoxin to identify and characterize them. The observed RR pattern and emission spectra show an association. The quality assessment of the commercial ultra-diluted organic drugs obtained from natural products may be initiated by monitoring in vivo studies on animal models. Anup Sharma and Bulbul Purkait Copyright © 2013 Anup Sharma and Bulbul Purkait. All rights reserved. Tue, 18 Dec 2012 09:49:41 +0000 http://www.hindawi.com/journals/jph/2013/906178/ In the present investigation, pulsatile release beads were prepared by ionic gelation technique. Lornoxicam dual cross-linked beads were prepared by dropping dispersed phase of lornoxicam, pectin, and sodium alginate into the dispersion phase of different concentrations of calcium chloride solution followed by aluminium chloride solution. The formulated beads were further coated by Eudragit L & S 100 in the ratio 1 : 2 w/w in order to achieve desired lag time. In vitro release study showed lag time of 5–8 h before release of lornoxicam from the formulated beads. Thus, formulated dual cross-linked beads when administered at bed time may release lornoxicam when needed most for chronotherapeutics of early morning rheumatoid arthritis attacks in chronic patients. Abanesh kumar Bansal and Vishal Pande Copyright © 2013 Abanesh kumar Bansal and Vishal Pande. All rights reserved. Thu, 06 Dec 2012 15:41:10 +0000 http://www.hindawi.com/journals/jph/2013/629593/ The objective of this study was to evaluate the influence of oxatomide β-cyclodextrin inclusion complex on the physicochemical properties and bioavailability of the drug. Oxatomide β-cyclodextrin solid complex was prepared with equimolar ratio of both oxatomide and β-cyclodextrin in presence or absence of water soluble polymers using different techniques. The coevaporated complex prepared in presence of PVP-K15 showed a prompt drug release and significantly increased % dissolution efficiency compared to the pure oxatomide. Moreover, the results of bioavailability evaluation of this complex in rabbits compared to commercial drug product indicated a 73.15% increase in the oral bioavailability of oxatomide. In conclusion, inclusion complex of oxatomide with β-cyclodextrin prepared by coevaporation in presence of PVP-K15 not only results in an enhancement of the oxatomide dissolution rate but also improves the bioavailability of oxatomide. Fahima M. Hashem, Mohamed Mostafa, Mahmoud Shaker, and Mohamed Nasr Copyright © 2013 Fahima M. Hashem et al. All rights reserved. Wed, 05 Dec 2012 14:27:56 +0000 http://www.hindawi.com/journals/jph/2013/892632/ The effect of hygrothermal conditions (air temperature and relative humidity) on the dehydration of theophylline monohydrate was investigated. Firstly, the equilibrium states of theophylline were investigated. The data from gravimetric analysis at constant temperature and humidity were reported as desorption isotherms. The PXRD analysis was used to identify the different polymorphic forms of theophylline: the monohydrate, the metastable anhydrate, and the stable anhydrate. Solid-solid phase diagrams for two processing times were proposed. Secondly, the dehydration kinetics were studied. The water content evolutions with time were recorded at several temperatures from 20°C to 80°C and several relative humidities from 4% to 50%. Different mathematical models were used to fit the experimental data. The spatially averaged solution of 2D Fickian transient diffusion equation best represented the water mass loss versus time experimental relationship. The dehydration rate constant was found to increase exponentially with air temperature and to decrease exponentially with air relative humidity. Amira Touil, Roman Peczalski, Souad Timoumi, and Fethi Zagrouba Copyright © 2013 Amira Touil et al. All rights reserved. Wed, 05 Dec 2012 14:12:12 +0000 http://www.hindawi.com/journals/jph/2013/103527/ Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed. Catherine Tomaro-Duchesneau, Shyamali Saha, Meenakshi Malhotra, Imen Kahouli, and Satya Prakash Copyright © 2012 Catherine Tomaro-Duchesneau et al. All rights reserved. Mon, 26 Nov 2012 11:45:03 +0000 http://www.hindawi.com/journals/jph/2013/792186/ The aim of study was to develop and validate two simple, sensitive, and extraction-free spectrophotometric methods for the estimation of risperidone in both pure and pharmaceutical preparations. They are based on the charge transfer complexation reactions between risperidone (RSP) as n-electron donor and p-chloranilic acid (p-CA) in method A and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in method B as π-acceptors. In method A, RSP reacts with p-CA in methanol to produce a bright pink-colored chromogen measured at 530 nm whereas, in method B, RSP reacts with DDQ in dichloromethane to form orange-colored complex with a maximum absorption at 460 nm. Beer's law was obeyed in the concentration range of 0–25 and 0–50 μg/mL with molar absorptivity of and L/moL/cm for RSP in methods A and B, respectively. The effects of variables such as reagents, time, and stability of the charge transfer complexes were investigated to optimize the procedures. The proposed methods have been successfully applied to the determination of RSP in pharmaceutical formulations. Results indicate that the methods are accurate, precise, and reproducible (relative standard deviation %). Hemavathi Nagaraju Deepakumari and Hosakere Doddarevanna Revanasiddappa Copyright © 2013 Hemavathi Nagaraju Deepakumari and Hosakere Doddarevanna Revanasiddappa. All rights reserved. Mon, 26 Nov 2012 08:37:16 +0000 http://www.hindawi.com/journals/jph/2013/396468/ The aim was to determine the release-modifying effect of carboxymethyl xyloglucan for oral drug delivery. Sustained release matrix tablets of tramadol HCl were prepared by wet granulation method using carboxymethyl xyloglucan as matrix forming polymer. HPMC K100M was used in a small amount to control the burst effect which is most commonly seen with natural hydrophilic polymers. A simplex centroid design with three independent variables and two dependent variables was employed to systematically optimize drug release profile. Carboxymethyl xyloglucan , HPMC K100M , and dicalcium phosphate were taken as independent variables. The dependent variables selected were percent of drug release at 2nd hour and at 8th hour . Response surface plots were developed, and optimum formulations were selected on the basis of desirability. The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours. The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (). Polynomial mathematical models, generated for various response variables using multiple regression analysis, were found to be statistically significant (). The statistical models developed for optimization were found to be valid. Ashwini R. Madgulkar, Mangesh R. Bhalekar, Rahul R. Padalkar, and Mohseen Y. Shaikh Copyright © 2012 Ashwini R. Madgulkar et al. All rights reserved. Sun, 25 Nov 2012 14:17:17 +0000 http://www.hindawi.com/journals/jph/2013/680580/ The purpose of study is to formulate and evaluate ufasomal gel of dexamethasone. Ufasomal suspension was made by sonication method using different concentrations of Span 80, Span 20 and cholesterol along with 25 mg of drug. Ufasomal gel was formulated by hydration method using carbopol 940. Ufasomal vesicles appeared as spherical and multilamellar under Transmission Electron Microscope. Ufasomal formulation prepared with drug to oleic acid molar ratio 8:2 (UF-2) produced greater number of vesicles and greater entrapment efficiency. UF-2 was optimized for further evaluation. The transdermal permeation and skin partitioning of from optimized formulation was significantly higher () as compared to plain drug and plain gel formulation which is due to presence of surfactant acting as permeation enhancer. Permeation of optimized formulation was found to be about 4.7 times higher than plain drug gel. Anti-inflammatory activity evaluated by inhibition Carrageenan induced rat paw edema model. Significant reduction of edema () was observed in comparison to the commercial product. Hence oleic acid based vesicles can be used as alternate carrier for topical delivery. Rajkamal Mittal, Arvind Sharma, and Sandeep Arora Copyright © 2013 Rajkamal Mittal et al. All rights reserved. Sun, 25 Nov 2012 09:01:45 +0000 http://www.hindawi.com/journals/jph/2013/546324/ The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed , prolonged absorption time, decreased , and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms. Bipul Nath and Lila Kanta Nath Copyright © 2013 Bipul Nath and Lila Kanta Nath. All rights reserved. Sat, 24 Nov 2012 14:47:45 +0000 http://www.hindawi.com/journals/jph/2013/983702/ Darifenacin is a urinary antispasmodic. The oral absorption of darifenacin is poor due to its low solubility and poor bioavailability (15–19%). Darifenacin was complexed with hydroxylropyl beta-cyclodextrin (Hpβ-CD). The best results were obtained with the coevaporation that interacts in a 1 : 1 drug : cyclodextrin molar ratio. The solid inclusion complexes were found to be amorphous in the characterization. The dissolution rate of darifenacin from the Hpβ-CD solid inclusion complex was increased compared to the powdered drug. The controlled release buccoadhesive patches for the delivery of darifenacin were prepared using HPMC K100M CR and HPMC K15. The coevaporation complex of the drug was used in the formulation due to its increased saturation solubility and increased ease of dissolution. The patches were evaluated for their surface pH, folding endurance, swelling, mucoadhesive properties, in vitro residence time, vapour transmission test, and in vitro and ex vivo release studies. Formulations Hb2 (2%) and Pb4 (4%) were found to be optimized. These two formulations can be used for buccal delivery of darifenacin which avoids first pass effect and leads to increased bioavailability of darifenacin. Swati C. Jagdale, Prachyasuman Mohanty, Aniruddha R. Chabukswar, and Bhanudas S. Kuchekar Copyright © 2013 Swati C. Jagdale et al. All rights reserved. Wed, 07 Nov 2012 10:02:15 +0000 http://www.hindawi.com/journals/jph/2013/381910/ Some pharmacodynamic effects of cefepime, a new injectable semisynthetic cephalosporin, were studied in laboratory animals and the following results were obtained. Cefepime maximally stimulated isolated guinea pig's ileum, rat's colon (80 μg/mL bath), and rabbit's duodenum (400 μg/mL bath). Contrarily, complete relaxation of isolated rat's fundic strip was produced by 80 μg/mL bath. Effects of cefepime on isolated rat's uterine muscle were different according to stage of sex cycle. Cefepime did not induce any effects on the resting tonus of isolated guinea pig's tracheal chain and rabbit's aortic strip. Concentrations of 200 and 400 μg/mL bath induced marked inhibition in the force of muscular twitches of the isolated frog's gastrocnemius muscle which was less potent than that induced by procaine hydrochloride 2%. Cefepime completely blocked the neuromuscular transmission of frog's rectus abdominis muscle (40 μg/mL bath) and rat's phrenic nerve hemidiaphragm preparation (200 μg/mL bath). This blockade was reversed by acetylcholine and neostigmine. Cefepime produced dose-dependent negative inotropic effect on isolated rabbit's heart and guinea pig's auricles. There were no changes in blood pressure and rate of respiration in anaesthetized dog after cefepime injection. These findings indicate that cefepime has a low potential to produce adverse reactions at therapeutic doses. Mossad Gamaleddin Ahmed Elsayed, Ashraf Abdelhakim Ahmed Elkomy, and Mohamed Elbadawy Copyright © 2013 Mossad Gamaleddin Ahmed Elsayed et al. All rights reserved. Sat, 03 Nov 2012 13:28:10 +0000 http://www.hindawi.com/journals/jph/2013/753928/ Nowadays monitoring pharmaceutical residues from surface waters is a widespread analytical task. Most of the studies are conducted from river waters or sewage treatment plants and mainly in Western Europe or North America. Such studies are seldom published from Eastern Europe, especially from stream waters, even though the prescription and consumption patterns of drugs as well as wastewater treatment procedures are very dissimilar. In Hungary the active substance of the most often prescribed drugs are cardiovascular and antiulcer agents. Hence in our study compounds belonging to these two groups were seasonally monitored in two main streams encompassing the Buda side of the Hungarian capital city and flowing into the Danube. To obtain data on the occurrence, fate, and seasonal variation of the compounds, samples were taken from altogether eleven points located near wastewater treatment plants and confluences. The results gave no identifiable pattern in the seasonal variation of concentrations but the contribution of the tributaries and wastewater treatment plants could be followed as expected. From the runoff corrected estuary concentrations the annual contribution of these streams to pharmaceutical pollution of the Danube could be estimated to be in excess of 1 kilogram for atenolol, famotidine, metoprolol, ranitidine, and sotalol. Renáta Varga, Iván Somogyvári, Zsuzsanna Eke, and Kornél Torkos Copyright © 2012 Renáta Varga et al. All rights reserved.