PREPARATION AND INVITRO CHARACTERISATION OF BOSENTAN MONOHYDRATE MUCOADHESIVE MICROSPHERES

Ch. S. Vijaya Vani and Vidyavathi Maravajala*

ABSTRACT

The present study involves the preparation and in vitro characterization of mucoadhesive microspheres of Bosentan Monohydrate a dual Endothelin receptor antagonist used in Pulmonary Arterial Hypertension with the aim to achieve controlled drug profiles in blood, to improve the therapeutic efficacy andthe patient compliance to use as an alternative therapy to conventional dosage form. The microspheres were prepared by emulsification solvent evaporation method using different polymer combinations in different ratios with HPMC K4M, HPMCK100M, Ethyl Cellulose andCarbopol 940P. Drug interaction studies by FTIR and DSC revealed that drug is compatible with the polymers in study. The prepared microspheres were charecterized for various parameters like particle size, practical yield, drug entrapment efficiency, swelling studies,in vitro drug release characteristics( in pH 1.2 buffer for first 2hrs, in pH 6.8 buffer up to 8 hrs and in pH 7.4 buffer up to 24 hrs.), in vitro mucoadhesion using goat intestine, muco adhesive strength and muco adhesive force. All the microspheres showed good swelling, mucoadhesive properties and good controlled release of drug. Among the different combinations of polymers in different ratios studied, the desired in vitro drug release(94.81% for 24 hrs) and highest in vitro mucoadhesion of 89% was found with the combination of Carbopol 940P and HPMC K100M with drug in the ratio of 1: 0.75:0.75(F3). The drug release from the F3 formulation followed Higuchi’s matrix and Peppa’s model.The invitro drug release of optimised formulation F3 was also compared with that of the marketed film coated tablets.The marketed formulation released 91% of drug with in one hour whereas the optimised formulation F3 showed a release of 94.81% of the drug over 24 hrs confirmed the prolonged release of the drug.

Keywords: Bosentan Monohydrate, Pulmonary Arterial Hypertension, Solvent evaporation,drug entrapment efficiency, in vitro mucoadhesion ,controlled release.