Formulation and Evaluation of Β-Cyclodextrin Inclusion Complexes of Dolutegravir Sodium for Solubility Enhancement

Abstract

Background: Dolutegravir sodium, a second-generation integrase strand transfer inhibitor used in the treatment of HIV, exhibits high permeability but poor aqueous solubility, thereby classifying it as a BCS Class II compound. Poor solubility limits its oral bioavailability, necessitating the development of formulation strategies to enhance dissolution and absorption. Objective: The present study aimed to enhance the solubility and dissolution rate of Dolutegravir sodium through the formation of β-cyclodextrin inclusion complexes and to evaluate the physicochemical and pharmaceutical properties of the prepared complexes and tablets. Methods: Phase solubility studies were performed following the Higuchi and Connors method to determine the stoichiometry of complexation. Inclusion complexes were prepared using the kneading technique and characterized by FTIR, DSC, XRD, drug content analysis, and in vitro dissolution studies. Tablets were formulated using the direct compression method with spray-dried lactose as a diluent. Stability studies were conducted under ambient and accelerated conditions for two months. Results: FTIR analysis confirmed the absence of chemical interactions between the drug and β-cyclodextrin, indicating compatibility. Phase solubility analysis revealed a 1:1 drug-to-β-cyclodextrin complex formation with a solubility enhancement ratio ranging from 1 to 4. DSC and XRD studies confirmed inclusion complex formation and the transformation of the drug into an amorphous form. The optimized formulation (F5) showed superior drug release—30.70%–38.57% at pH 1.2 and 88.58%–98.60% at pH 6.8—outperforming the marketed formulation. The prepared tablets exhibited excellent flow and compressibility, and stability studies demonstrated no significant change in drug content or dissolution profile. Conclusion: The study concludes that inclusion complexation of Dolutegravir sodium with β-cyclodextrin effectively enhances its solubility and dissolution rate, thereby potentially improving its oral bioavailability. The optimized formulation (F5) demonstrated stability and superior performance compared to the marketed product, making it a promising approach for improving the therapeutic efficacy of Dolutegravir sodium.