Effect of Formulation Variables on Optimization of Gastroretentive In Situ Rafts of Bosentan Monohydrate HCl by 32 Factorial Design

Abstract

Objectives The study was focused to prepare gastro retentive in situ rafts a controlled release dosage form of Bosentan monohydrate hydrochloride (BMH) through which the administration by oral route becomes easier and retain the drug more time in the stomach, at its absorption window. Materials and Methods Nine (F1–F9) gastro retentive in situ rafts of BMH were formulated using 32 factorial design by taking ratio of polymers, sodium alginate and pectin (X1) and quantity of effervescent (X2) as two variables at 3 levels and characterized to find out the influence of two variables on Gel strength (Y1), Floating time (Y2), Floating lag time (Y3), in vitro drug release (Y4), Viscosity, Gelling time and Drug content. Then, the results of all responses (Y1–Y4) were fit into mathematical model as per the design. Results Release kinetic studies revealed that, F6 formulation shown first order release as the best fit model. Polymers sodium alginate and pectin were found to possess good compatibility with BMH without any mutual interaction as per DSC and FTIR spectra. The best selected formulation F6 has shown in vitro sustained drug release up to 12 h which was also confirmed by in vivo X-ray image studies in rabbits. Conclusion The best selected formulation F6 was found to process in vitro extended release up to 12 h which was also confirmed by in vivo X-ray image studies in rabbits. The stability studies, revealed that, there was no noticeable variation in drug content, floating ability during stability studies.