FORMULATION ANDCHARACTERIZATION OF OLANZEPINELOADED MUCOADHESIVE MICROSPHERES

Objective: The objective of this research was to formulate and evaluate olanzapine (OLE) mucoadhesive microsphere prepared using carbopol and sodium combination. OLE having extensive hepatic first pass metabolism and low bioavailability problem, determined the need for the development of sustained release formulation.Methods: OLE mucoadhesive microspheres were prepared by ionic gelation method. OLE mucoadhesive microspheres were prepared by ionic gelation method by using calcium chloride as crosslinking agent. The OLE mucoadhesive microsphere was characterized by particle size measurement, process yield, morphology of microsphere, drug entrapment efficiency, mucoadhesion test, differential scanning calorimetry, powder X-ray diffraction, Fourier transforms infrared (FTIR) study and in-vitro drug release.Results: The OLE mucoadhesive microsphere having mean particle size ranged from 546.0 µm to 554.3 µm, and the entrapment efficiencies ranged from 73% to 96%. All the olanzapine (OLE) microsphere batches showed good in-vitro mucoadhesive property ranging from 75.89% to 96.47% and in the in-vitro wash off test ranging from 68.12% to 81.3%. FTIR studies indicated the no drug-polymer interactions in the ideal formulation F9. Therewere no compatibility issues, and the crystallinity of OLE was found to be reduced shoeing less intense peak in prepared mucoadhesive microspheres, which were confirmed by differential scanning calorimeter and X-ray diffraction studies. Among different formulations, the OLE microspheres of batch F9 had shown the optimum percent drug entrapment of microspheres. Release pattern of OLE from F9 microspheres batch followed Higuchi kinetic model. Stability studies were carried out for F9 formulation at 4°C/ambient, 25±2°C/60±5%, 40±2°C/75±5% relative humidity revealed that the drug entrapment, mucoadhesive behavior, and drug release were within permissible limits.Conclusion: The results obtained in this work demonstrate the use of carbopol and sodium alginate polymer for preparation of mucoadhesive microsphere.Keywords: Ionic gelation method, Gastroretentive delivery, Mucoadhesive microsphere, Carbopol

IMMEDIATE RELEASE SOLID DISPERSION TABLET OF AZILSARTAN: FORMULATION STRATEGY TO ENHANCE ORAL BIOAVAILABILITY

Objective: Objective of the present study was to develop an immediate release solid dispersion tablet to enhance oral bioavailability of Azilsartan. Methods: Solid dispersion of azilsartan was developed using Soluplus® as a novel solubility enhancer by the solvent evaporation technique. 32factorial design was used in a fully randomized order to study effect of amount of azilsartan and Soluplus on solubility (µg/ml) and % drug dissolved in 30 min. Prepared solid dispersion was evaluated for different micromeritic properties, saturation solubility, and wettability. Then solid dispersion of all the batches compressed into an immediate-release tablet using sodium starch glycolate as a super disintegrant. Developed tablet formulations were evaluated for various post-compression parameters and satisfactory formulation among these were further studied for Fourier-transform infrared spectroscopy (FTIR), Differential Scanning Colorimeter (DSC), X-Ray Diffraction (XRD), in vivo absorption and stability study. Results: Results of micromeritic properties of solid dispersion showed that good flowability, compressibility, wettability, and saturation solubility. Post compression parameters of immediate-release tablets were found to be in acceptable limits. Batch ASD2 containing 40 mg Diacerein and 80 mg of Soluplus showed maximum drug release i.e. 99.82 % within 30 min. Compatibility study using FTIR, DSC, and XRD showed that drug is compatible with Soluplus. In vivo absorption study showed that, 2.67 fold increase in Area Under Curve (AUC) as compared to plain Azilsartan. Relative bioavailability was found to be 267.11 %. Results of stability study indicate that developed formulations were stable at accelerated temperature and humidity conditions. Conclusion: Study concluded that solid dispersion using Soluplus as a solubility enhancer is a suitable formulation strategy to enhance solubility, dissolution, and bioavailability of poorly water-soluble drug-like Azilsartan

DEVELOPMENT OF SOLID SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM OF DIACEREIN FOR ENHANCED DISSOLUTION RATE

Objective: The objective of the present study was to develop solid self-microemulsifying drug delivery system (S-SMEDDS) of diacerein (DCN) for enhancement of dissolution rate. Methods: Three batches of liquid SMEDDS were prepared using oleic acid, Tween 80, and polyethylene glycol 200 as oil, surfactant, and cosurfactant, respectively. Microemulsion region was recognized by constructing a pseudoternary phase diagram containing a different proportion of oil, surfactant, and cosurfactant. Prepared liquid SMEDDS was evaluated for thermodynamic stability study, dispersibility tests, globule size, zeta potential, and viscosity. Liquid SMEDDS was then converted to S-SMEDDS by adsorption technique using Neusilin US2 as a solid carrier. Prepared S-SMEDDS was evaluated for different micromeritic properties, drug content, reconstitution properties, in vitro dissolution study, Fourier transform infrared, and scanning electron microscopy. Results: The results showed that all batches of liquid SMEDDS were found to be thermodynamically stable. Reconstitution properties of S-SMEDDS showed spontaneous microemulsification with globule size 0.271 μm and −16.18 mV zeta potential. From the results of in vitro dissolution study, it was found that the release of DCN was significantly increased as compared with plain DCN. Conclusion: The study concluded that dissolution rate of poorly water-soluble drug like DCN can be increased by developing S-SMEDDS formulation

Disseminated peritoneal hydatidosis following blunt abdominal trauma: A case report

A middle age lady presented with abdominal pain was diagnosed to have multiple peritoneal and hepatic hydatid cysts on CT scan. Retrospectively she was found to have suffered blunt abdominal trauma

DESIGN, DEVELOPMENT AND CHARACTERIZATION OF PACLITAXEL LOADED SOLID LIPID NANOPARTICLES AS A COLLOIDAL DRUG CARRIER

Objective: This study was aimed to design and characterize Paclitaxel-loaded Solid Lipid Nanoparticles (SLNs) to achieve site specificity,reduce toxicity and sustained release pattern. Methods: Paclitaxel-loaded solid lipid nanoparticles were fabricated by microemulsion followed by probe sonication technique using stearic acid as lipid and stabilized of the mixture of surfactants. In this study, 32 full factorial design was employed for optimizing the concentration of lipid as stearic acid and surfactant (soya lecithin) for the nanoparticles. The optimization was done by studying the dependent variable of particle size and % entrapment efficiency. Results: The results showed that the paclitaxel-loaded solid lipid nanoparticles prepared with the concentration of 33.31 % stearic acid and 500 mg of soya lecithin were optimum characteristic than other formulations. They showed the average particles size 149±4.10 nm and PDI 250±2.04. The zeta potential, % EE and % drug loading capacity was found to be respectively-29.7, 93.38±1.90 and 0.81±0.01. The optimized batch of Paclitaxel SLNs exhibited spherical shape with smooth surface analyzed by Transmission Electron Microscopy. In vitro study showed sustained release profile and was found to follow Higuchi Kinetics Equation. Conclusion: The SLNs of paclitaxel m et al. l the requirements of a colloidal drug delivery system. They had a particle size in nanosize; their size distribution was narrow and all the particles were in a spherical shape

Synthesis and antimicrobial studies on novel sulfonamides containing 4-azidomethyl coumarin

A series of new and novel coumarin-6-sulfonamides with a free C4-azidomethyl group have been synthesized as antimicrobials in three steps starting from 7-methyl-4-bromomethylcoumarin 1. The reaction of 1 with chlorosulfonic acid was found to yield the corresponding 6-sulfonylchloride 2, which when treated with sodium azide led to intermediate 3. The title sulfonamides 5a-y were obtained from the reaction of 3 with various aromatic amines 4 in refluxing benzene. The chemical structures of the compounds were elucidated by IR, NMR and LC-MS spectral data. All the synthesized compounds have been screened for their in vitro anti-bacterial and anti-fungal activities. Some of the compounds have been found to be active against both bacterial species at a concentration of 1 μg/mL. © 2009 Elsevier Masson SAS. All rights reserved