STUDIES IN OXCARBAZEPINE MICROSPHERES EMPLOYING PLACKETT AND BURMAN DESIGN

Objective: The present work was aimed to screen material and processing parameters affecting encapsulation efficiency and drug release from microspheres. Methods: Oxcarbazepine loaded microspheres were prepared employing multiple emulsion solvent evaporation technique. Ratio of chitosan to ethyl cellulose, ratio of drug to polymer, stirring speed, ratio of dichloromethane to methanol, amount of Span 80 and the volume of aqueous phase were selected as independent variables in the Plackett and Burman design. The microspheres were characterized for percentage yield, percentage encapsulation efficiency, particle size distribution and in vitro drug release. Results: The critical material and processing parameters affecting encapsulation efficiency were chitosan to ethyl cellulose ratio, volume of water, stirring speed and drug to polymer ratio. Initial burst release was affected by volume of water, temperature, dichloromethane to methanol ratio, amount of Span 80 and drug to polymer ratio. FTIR study showed compatibility of the drug with excipients. Conclusion: The outcome of the study shall be used to calculate risk priority number (RPN) and for devising suitable control strategies for the critical factors at industry

Development and optimization of self microemulsifying drug delivery of domperidone

The present investigation is aimed to develop self-microemulsifying drug delivery system (SMEDDS) to improve the in vitro dissolution of a BCS (Biopharmaceutical Classification System) class II anti emetic agent, domperidone. Solubility study was performed to identify the ingredients showing highest solubility of domperidone. The ternary phase diagrams were plotted for selected components to identify the area of microemulsion existence. D-optimal mixture experimental design was applied to optimize a liquid SMEDDS using formulation variables; the oil phase X1 (Oleic acid), the surfactant X2 (Labrasol) and the co-surfactant X3 (Transcutol HP). The liquid SMEDDS were evaluated for droplet size, emulsification time, % transmittance and drug release. Stability study was performed at 40 °C/75% RH. Liquid formulation was solidified by adsorption on carrier Aerosil 300. Solid SMEDDS was evaluated and compared with liquid SMEDDS and marketed formulation. Oleic acid was selected as oil, Labrasol as surfactant and Transcutol HP as co-surfactant for formulation of SMEDDS. The optimized batch showed best results in terms of smaller droplet size (O presente estudo teve como objetivo desenvolver sistemas de liberação auto-microemulsificantes (Self-Microemulsifying Drug Delivery System - SMEDDS) de domperidona, agente antiemético, classe II, segundo o sistema de classificação Biofarmacêutica, para melhorar sua dissolução in vitro. Estudo foi realizado para identificar os componentes que revelaram maior solubilidade da domperidona. Determinaram-se os diagramas de fase ternários para esses componentes selecionados tendo em vista a identificação da região de formação da microemulsão. O planejamento experimental foi empregado para otimizar os SMEDDS líquidos, utilizando as seguintes variáveis de formulação: a fase oleosa X1 (ácido oleico), o agente tensoativo X2 (Labrasol) e co-tensoativo X3 (Transcutol HP). Os SMEDDS líquidos foram avaliados quanto às seguintes características: tamanho da gota, tempo de emulsificação,% de transmitância e liberação do fármaco. O estudo de estabilidade foi realizado a 40 °C/75% de umidade relativa. A formulação foi convertida em forma sólida por sua adsorção em Aerosil 300. Os SMEDDS sólidos foram avaliados e comparados com SMEDDS líquidos e a formulação comercializada. O ácido oléico foi selecionado para a fase oleosa, Labrasol como agente tensoativo e Transcutol como co-tensoativo para a formulação de SMEDDS. O lote otimizado mostrou os melhores resultados: menor tamanho de gota

DEVELOPMENT OFRIZATRIPTAN BENZOATE MICROSPHERES FOR NOSE TO BRAIN TARGETING

Objective: Oral administration of rizatriptan benzoate shows poor bioavailability due to first pass metabolism, which can be avoided by nasal administration of drugs. Additionally, the nasal administration provides faster onset of action, which is desired to get relief from the intense pain of a migraine. The present research work was emphasised on design, development and evaluation of mucoadhesive microspheres for nasal delivery of rizatriptan benzoate through a systematic approach. Methods: The microspheres of rizatriptan benzoate were prepared by the w/o/w double emulsion solvent diffusion method using the non-aqueous medium. Critical formulation and process parameters were identified through preliminary trial batches and 2[4-1] fractional factorial design was employed using polymer concentration (X1:2-5%), drug to polymer ratio (X2:1:2-1:6), amount of liquid paraffin (X3:100-200 ml) and the amount of magnesium stearate (X4:100-150 mg) as independent variables. Results: Design batches were evaluated for percent yield (50-78%), percent entrapment efficiency (62-85%), drug loading (7.5-30%), % mucoadhesion (47-75%) and drug release at 6 h (44-78%). Scanning electron microscopic (SEM) study showed that microspheres were of 50 µm in size and spherical in shape with a smooth surface. The optimised batch (D10) showed 85% entrapment efficiency and 66.6% drug release within 6 h. The developed microspheres could be used to deliver rizatriptan benzoate through nasal administration for treatment of a migraine. Conclusion: The developed microspheres can be considered as a promising system for nasal delivery system of rizatriptan benzoat

Anti-Inflammatory and Antioxidative Stress Effects of Oryzanol in Glaucomatous Rabbits

Purpose. γ-Oryzanol works by anti-inflammatory and radical scavenging activity as a neuroprotective, anticancer, antiulcer, and immunosuppressive agent. The present study was conducted to investigate effect of oryzanol in acute and chronic experimental glaucoma in rabbits. Methods. Effect of oryzanol was evaluated in 5% dextrose induced acute model of ocular hypertension in rabbit eye. Chronic model of glaucoma was induced with subconjunctival injection of 5% of 0.3 ml phenol. Treatment with oryzanol was given for next two weeks after induction of glaucoma. From anterior chamber of rabbit eye aqueous humor was collected to assess various oxidative stress parameters like malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, nitric oxide, and inflammatory parameters like TNF-α and IL-6. Structural damage in eye was examined by histopathological studies. Results. In acute model of ocular hypertension oryzanol did not alter raised intraocular pressure. In chronic model of glaucoma oryzanol exhibited significant reduction in oxidative stress followed by reduction in intraocular pressure. Oryzanol treatment reduced level of TNF-α and IL-6. Histopathological studies revealed decreased structural damage of trabecular meshwork, lamina cribrosa, and retina with oryzanol treatment. Conclusions. Oryzanol showed protective effect against glaucoma by its antioxidative stress and anti-inflammatory property. Treatment with oryzanol can reduce optic nerve damage

Drug Design, Synthesis and Biological Evaluation of Heterocyclic Molecules as Anti-Inflammatory Agents

Non-steroidal anti-inflammatory drugs (NSAIDs) are generally utilized for numerous inflammatory ailments. The long-term utilization of NSAIDs prompts adverse reactions such as gastrointestinal ulceration, renal dysfunction and hepatotoxicity; however, selective COX-2 inhibitors prevent these adverse events. Various scientific approaches have been employed to identify safer COX-2 inhibitors, as in any case, a large portion of particular COX-2 inhibitors have been retracted from the market because of severe cardiovascular events. This study aimed to develop and synthesize a novel series of indomethacin analogues with potential anti-inflammatory properties and fewer side effects, wherein carboxylic acid moiety was substituted using DCC/DMAP coupling. This study incorporates the docking of various indomethacin analogues to detect the binding interactions with COX-2 protein (PDB ID: 3NT1). MD simulation was performed to measure the stability and flexibility of ligand–protein interactions at the atomic level, for which the top-scoring ligand–protein complex was selected. These compounds were evaluated in vitro for COX enzymes inhibition. Likewise, selected compounds were screened in vivo for anti-inflammatory potential using the carrageenan-induced rat paw oedema method and their ulcerogenic potential. The acute toxicity of compounds was also predicted using in silico tools. Most of the compounds exhibited the potent inhibition of both COX enzymes; however, 3e and 3c showed the most potent COX-2 inhibition having IC50 0.34 µM and 1.39 µM, respectively. These compounds also demonstrated potent anti-inflammatory potential without ulcerogenic liability. The biological evaluation revealed that the compound substituted with 4-nitrophenyl was most active