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

Objective: Atazanavir (ATZ) sulfate is widely prescribed as an antiretroviral drug belonging to BCS class II with low solubility. This research aims to design, formulate, and optimization of floating sustained-release tablets of ATZ through Box-Behnken design (BBD). Method: The formulation parameters were optimized using the BBD. Methocel K100M (A) was chosen as the primary release-retarding polymer, Sodium Bicarbonate (B) served as the gas-generating agent, Ethyl Cellulose (C) was utilized as an additional release-retarding polymer, and Cetyl Alcohol as a floating assistant. In this design, A, B, and C were designated as independent variables, while three response variables floating lag time (FLT) (Y1), swelling index (Y2), and percentage drug release (Y3) were selected as the dependent variables. The compatibility of the drug and excipients was evaluated through Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and morphology by scanning electron microscopy. Tablets were prepared through the direct compression method and subsequently evaluated for parameters including FLT, flotation time, swelling index, hardness, drug content, friability, in vitro drug release, and drug release kinetics. Results: FTIR and DSC investigations revealed no interaction between the drug and the excipients, physical mixture of the drug and the excipients indicated the amorphous state of ATZ. All the evaluated tablets showed satisfactory results. The drug release from the validated optimized tablets was gradual and sustained over 12 h (99.76±0.75) following zero-order kinetics. Conclusion: The optimized tablets with desirable formulation characters were determined through a statistical optimization model and the optimized formulation remarkably sustained the drug release for up to 12 h, indicating its improved therapeutic potential for the treatment of HIV.