The aim of the present study was to develop and optimize the self-microemulsifying drug delivery formulation of\nbosentan monohydrate (BM) and assess the pharmacokinetic parameters in rats. Poor aqueous solubility of bosentan\nmonohydrate (BM) is a major determinant of its low oral bioavailability. Screening of various components of SMEDDS was done\nby solubility study. Clove oil as oil, tween 80 and labrasol as surfactants, PEG 400 as co-surfactant and ethanol (99.5 %w/v) as\nco-solvent to minimize the chance of drug precipitation were chosen for SMEDDS formulation. Pseudoternary phase diagram\nwas plotted to identify the self-emulsification region and surfactant to co-surfactant ratio. Further formulation was optimized by\napplying D-optimal mixture design with three independent variables X1 (Oil %w/w), X2 (Surfactants %w/w) and X3 (cosurfactant\n%w/w). Predicted compositions were evaluated for two responses: globule size (nm) and %transmittance.\nEnhancement of bioavailability was confirmed by pharmacokinetic study in rats. Optimized batch containing 12.5 mg of BM drug\nloading was predicted to 9% w/w clove oil, 56% w/w surfactant mixture (tween 80 and labrasol), 33% w/w PEG 400 and\n2%w/w ethanol (99.5%w/w) using design. Responses were predicted to 15.29 nm globule size and 99.7 % transmittance with\n0.976 batch desirability. Good agreement was observed between experimental and predicted responses. From the\nbioavailability study it was found that BM SMEDDS shows 2.55 times improvement in oral bioavailability compared to standard\nsuspension of BM in rats.
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