Design and Development of Darunavir loaded Self Micro Emulsifying Drug Delivery System using Extreme Vertices Mixture Design in a Quality by Design Framework

Abstract:

Aim: The therapeutic utility of many poorly water-soluble drugs are severely restricted for their bioavailability. The present study was aimed to development of self-micro emulsifying drug delivery (SMEDDS) system for a poorly water soluble anti-retroviral drug - Darunavir by the application of Quality by Design (QbD) to increase its bioavailability. Methodology: Extreme Vertices Mixture Design (EVMD), based on its utility and the applicability to the formulation problem in hand was selected for the study. The different responses selected for this design were drug release in 15 min (%), drug loading (mg/ml), emulsification time (seconds) and droplet size (nm). The factors or the independent variables considered in the design are oil, surfactant and cosurfactant. Ten different formulations were prepared and evaluated to check the model fit. The optimization and model verification were done by conducting experimental runs. Results: The studies revealed that application of EVMD and development of the formulation in a QbD framework resulted in a robust and sustainable method for improving the bioavailability of the drug as evidenced by the characterization studies of optimized batch In vitro drug release in 15 min (92.43 %), drug loading (98.95 mg/ml), emulsification time (31.5 sec) and droplet size (222.2 nm). The Transmission electron micrographs (TEM) obtained for optimized formulation showed a uniform spherical morphology. Conclusion: The development of hard to achieve formulation techniques like SMEDDS involving BCS class 2 and 4 drugs can be sustainably achieved with minimal time and resources, matching regulatory requirements can be attained by the application of EVMD, under QbD framework.

Key words: Antiretroviral, Darunavir, Extreme vertices, Self-emulsified system, QbD.