Quality by Design Based Development of Self Nano Emulsifying Drug Delivery System of Ritonavir

Abstract

Objectives: Ritonavir is an antiretroviral agent which belongs to Biopharmaceutical Classification System (BCS) II having poor water solubility. The purpose of this study was to design Self-Nano Emulsifying Drug Delivery System (SNEDDS) for a poorly water-soluble anti-retroviral drug-Ritonavir by implementing Quality by Design (QbD). Methods: In a DoE based development, Mixture design was used for the development and simultaneous optimization of the Ritonavir-SNEDDS. Droplet size (nm), Emulsification time (seconds), Polydispersity Index (PDI) and % Transmittance were the various responses selected for the study. Labrafil® M 1944 CS (oil), Tween 80 (surfactant) and PEG 6000 (cosurfactant) are the independent variables considered in the design. Eight formulations were prepared and tested for model fit. The simultaneous optimization of formulation was done by the Global desirability function approach obtained through Prediction profiler. Results: The developed optimal Ritonavir -SNEDDS through QbD approach resulted in a robust and sustainable method for improving the oral bioavailability of Ritonavir and confirmed by the characterisation studies- droplet size (264.7 nm), emulsification time (46.1 sec), PDI (0.415) and % transmittance (94.8). Conclusion: The results conclude the potentiality of SNEDDS formulation to improve Ritonavir oral bioavailability under the QbD framework. Key words: Critical Material attributes, Critical Quality Attributes, Quality by design Ritonavir, Self-Nano Emulsifying Drug Delivery System (SNEDDS), Smix, Risk Estimation Matrix.