ABSTRACT:
Adoption of Novel Drug Delivery System approaches to make therapeutically viable formulation of BCS class 2 & 4 is most followed approach. In this work the Etravirine (ETV) is formulated as a SMEDDS formulation in a lean QbD approach and it was characterized by conventional In-vitro methods further augmented by Insilco approaches as well. The Critical Quality Attributes (CQAs) drawn from the Quality Target Product Profile (QTPP) were coded into the Extreme Vertices Mixture Design (EVMD) and the factors that would return with the required responses were identified and optimized. The optimized formulation method was characterized by In-vitro methods and also was further augmented with the application of Insilco prediction methods to understand the In-vivo performance characteristics of the formulation. The ETV drug showed Papp value of zero and was considered to have poor permeability. Whereas, SMEDDS formulation of ETV exhibited a Papp value of 2.63X10-6cm/s. The cell line study confirms the enhancement in the permeability of BCS Class 4 drug through dissolution enhancement of drug, and increased mucosal permeability due to the presence of lipoidal excipients in the formulation. The Monte Carlo population simulation predicted the Cmax and Tmax of 0.57729ug/ml and 3.9624h respectively for ETV-SMEDDS. The percentage bioavailability was predicted at 91.67% for the formulation. The research work confirms the better identification of formulation problems with minimal resources commitment and also develops a robust scalable process with knowledge to design space transition.