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Inventi Impact - NDDS

Articles

  • Inventi:pndds/23828/17
    DEVELOPMENT AND OPTIMIZATION OF SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM FOR BOSENTAN MONOHYDRATE BY D-OPTIMAL MIXTURE DESIGN: IN-VITRO AND IN-VIVO EVALUATION
    Ankit Patel, Nilima Pandya, Hemal Tandel*

    The aim of the present study was to develop and optimize the self-microemulsifying drug delivery formulation of bosentan monohydrate (BM) and assess the pharmacokinetic parameters in rats. Poor aqueous solubility of bosentan monohydrate (BM) is a major determinant of its low oral bioavailability. Screening of various components of SMEDDS was done by solubility study. Clove oil as oil, tween 80 and labrasol as surfactants, PEG 400 as co-surfactant and ethanol (99.5 %w/v) as co-solvent to minimize the chance of drug precipitation were chosen for SMEDDS formulation. Pseudoternary phase diagram was plotted to identify the self-emulsification region and surfactant to co-surfactant ratio. Further formulation was optimized by applying D-optimal mixture design with three independent variables X1 (Oil %w/w), X2 (Surfactants %w/w) and X3 (cosurfactant %w/w). Predicted compositions were evaluated for two responses: globule size (nm) and %transmittance. Enhancement of bioavailability was confirmed by pharmacokinetic study in rats. Optimized batch containing 12.5 mg of BM drug loading was predicted to 9% w/w clove oil, 56% w/w surfactant mixture (tween 80 and labrasol), 33% w/w PEG 400 and 2%w/w ethanol (99.5%w/w) using design. Responses were predicted to 15.29 nm globule size and 99.7 % transmittance with 0.976 batch desirability. Good agreement was observed between experimental and predicted responses. From the bioavailability study it was found that BM SMEDDS shows 2.55 times improvement in oral bioavailability compared to standard suspension of BM in rats.

    How to Cite this Article
    Ankit Patel, Nilima Pandya, Hemal Tandel. Development and Optimization of Self- Microemulsifying Drug Delivery System for Bosentan Monohydrate by D-Optimal Mixture Design: In-Vitro and In-Vivo Evaluation. Inventi Impact: NDDS, 2018(1):1-15, 2018.
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