FORMULATION AND OPTIMIZATION OF FLOATING SUSTAINED RELEASE TABLETS OF RITONAVIR THROUGH BOX-BEHNKEN DESIGN

Objective: The purpose of this study is to design and evaluate floating sustained-release tablets of ritonavir (RTZ) employing box-behnken development (BBD). Methods: The BBD was utilized to improve the formulation parameters. The main release-retarding polymers were selected as independent variables: methocel K100M (A), the gas-generating agent was sodium bicarbonate (B), the secondary release-retarding polymer was ethyl cellulose (C), and the floating aid was Cetyl alcohol and which was kept constant. Floating lag time (FLT) (Y1), swelling index (SI) (Y2), and percentage drug release (Y3) were chosen as the dependent variables. Differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) were used to assess the compatibility of the drug and excipient. FLT, flotation time, SI, hardness, drug content, friability, in vitro drug release, and drug release kinetics were assessed after the tablets were manufactured using the direct compression method. Results: FTIR and DSC analyses showed no interaction between the drug and the excipients. Every tablet that was tested produced positive outcomes. The validated optimized (VO) tablets exhibited zero-order kinetics, with a steady and sustained drug release over 12 hours (95.76±0.75 %), FLT of VO formulation was found to be 53±0.5sec with 91.21±1.6% of SI. In vivo bioavailability of optimized formulation shows a 1.5-fold increase in bioavailability. Conclusion: Using a statistical optimization model, the optimized tablets with the desired formulation characteristics were identified. The optimized formulation remarkably maintained the drug release for up to 12 hours, suggesting improved therapeutic potential for HIV therapy.