V. Sai Kishore

  The aim of the present work was to improve the solubility and dissolution rate of simvastatin, a drug used for the treatment of hyperlipidemia. Simvastatin is a selective competitive inhibitor of HMG CoA reductase. However its absolute bioavailability is 5 %. To increase the solubility of drug solid dispersion was prepared. Solid dispersion preliminary solubility analysis was carried out for the selection of carriers and solid dispersion was prepared with PEG 4000 and PVP-K30. These solid dispersions were analyzed for the solubility and In-vitro dissolution profile, solid dispersion of drug with PEG 4000 had shown enhanced solubility with improved dissolution rate. Further FTIR, X-Ray studies were carried out. Solid dispersion prepared with PEG 4000 in 1:5 ratio shows the presence of amorphous form confirmed by the characterization study .The study also shows the that dissolution rate of Simvastatin can be enhanced to considerable extent by solid dispersion technique with PEG4000. Key words: Hyperlipidemia, solid dispersion, PEG4000, PVP-K30.

  Diltiazem hydrochloride, a calcium channel blocker, is widely used for the treatment of angina pectoris, hypertension and arrhythmias. The usual dose of diltiazem hydrochloride is 180-240 mg/day. The conventional tablet or capsule is administered 3 or 4 times a day due to its low biological half-life of about 3.7 h. The problems of frequent administration and variable low bioavailability (36-50%) after oral administration of conventional tablet or capsules have been attenuated by designing diltiazem hydrochloride in the form of mucoadhesive microspheres. Diltiazem hydrochloride loaded mucoadhesive microspheres were successfully prepared by emulsification-internal gelation technique with a maximum encapsulation efficiency of 99.48± 0.32%.The order of increasing release rate observed with various microspheres was as follows Sodium alginate < Sodium alginate+ NaCMC < Sodium alginate+ HPMC. The order of increasing release rate observed with various cross linking agents was as follows Aluminum chloride < Barium chloride< Calcium chloride. The release behaviour of microspheres, with different cross-linking agents depends upon the valency and size of the cations of the respective cross-linking agent. The dissolution profiles follow zero order kinetics and the mechanism of drug release was governed by peppas model. The in vitro wash-off test indicated that the wash-off was faster at simulated intestinal fluid (phosphate buffer, pH 7.4) than that at simulated gastric fluid (0.1 M HCl, pH 1.2). The mucoadhesive microspheres formulated with sodium alginate+HPMC and calcium chloride showed a satisfactory sustained release profile for 12 hours.