Formulation and Evaluation of Dolutegravir Proliposomal Powder for Pediatric HIV Patients

Abstract

Objectives: The objective of the present study was to improve the absorption of dolutegravir sodium by developing oral proliposomal formulation. Methods: Proliposomal formulations were prepared by film deposition on carrier method using cholesterol along with various lipids and different carriers. Three factors (independent variables) such as different lipids (X1), different carriers (X2) and different ratio of lipid: cholesterol (X3) were studied at all three levels, while % entrapment efficiency (%EE) (Y) was taken as the response (dependent variable). The proliposomes were optimized by Taguchi OA (L9) experimental design using Minitab 18 English software. Results and Discussion: Proliposomes were evaluated and the % EE of optimized proliposomal formulation (PL7) found to be 84.02 %. In vitro drug release was performed in 0.1N HCl and in 6.8 pH phosphate buffer with SLS using USP type II dissolution apparatus, the % drug release found to be 12.71 % in 120 min. and 98.95% in 80 min. respectively, which indicates the drug is not released in acidic medium. Surface morphology was coarse, non-porous and irregular in shape, hydration is rapid and complete conversion of proliposomes to liposomes vesicles within 2-3 min. The mean particle size is 276.6 nm, polydispersity index is 0.329 and zeta potential is -9.54 mV, may prevent aggregation of vesicles and formulation is stable. Ex-vivo absorption studies were done using the rat non-everted intestinal sac model, permeation studies revealed that Papp of the optimized proliposomal formulation and IR tablet found to be 1.19 and 0.995 cm/sec respectively indicates enhanced absorption than the pure IR tablet. Conclusion: The proliposomal formulation indicated a stable formulation with significant improvement in absorption of dolutegravir sodium.