FORMULATION AND DEVELOPMENT OF BOSENTAN LOADED ONCE A DAILY TABLET FOR PULMONARY ARTERY HYPERTENSION USING LIPID MATRICES BY 32 FULL FACTORIAL DESIGN

To avoid problems of conventional therapy of drug delivery and reduced dose, sustained release matrix tablet of Bosentan was prepared using lipid base material as matrices. Primary screening of polymer was done by selecting different lipid base materials like Compritol 888 ATO, Precirol ATO 5, Eudragit RSPO, Glycerly monostearate (GMS) and cetosteryl alcohol. All the batches were prepared by direct compression method. Theoretical drug release profile was carried out for dose calculation up to 24 h. All the batches were evaluated for hardness, weight variation, thickness and friability (physicochemical parameters). In-vitro drug release and FTIR study was carried out along with experimental design. From the drug release profile it was observed that Compritol 888 ATO (F1) shows batter retardant effect and Precirol ATO 5 (F2) shows effective burst release. But remaining formulations (F3-F5) were not able to release the drug as per theoretical drug release profile. After selecting lipid matrices it was optimized by 3² full factorial design by applying analysis of variance (ANOVA). Concentration of Compritol 888 ATO and Precirol ATO 5 were selected as independent factor and time require for 20% drug release (Y1) and time require for 80% drug release (Y2) were selected as response. Optimized batch showing drug release 99.45% at 24 h. With desire burst release. Pharmacokinetic study shows best fit model is Higuchi model having R² value 0.9886. Combination of two lipid base material Compritol 888 ATO and Precirol ATO 5 shows most desire sustained release as compare to individual.