Efavirenz cocrystals with Ascorbic acid: A Strategy for Polymorphic Modification and improvement of Dissolution properties

Abstract

The objective of this research was to improve the solubility and dissolution rate of Efavirenz (EFA), a BCS II drug utilized for HIV infection treatment, by cocrystallization with ascorbic acid (AA). An in silico analysis indicated that EFA and AA exhibited physical interaction and compatibility. EFA exists in two polymorphic forms, I and II, with varying crystalline habits, where polymorph II presents better solubility and dissolution rate. Cocrystals were prepared using the solvent evaporation method by varying AA concentration and temperature. FTIR and NMR analysis confirmed the absence of chemical interaction between EFA and AA. Increasing AA concentration and temperature significantly increased the saturation solubility. DSC, XRD and SEM analysis revealed a shift in the endothermic peak of EFA, change in intensity with 2θ values, and modified surface morphology respectively. This also confirmed a polymorphic structure change in the cocrystals due to high heating rates and maximum crystallization rate. The dissolution rate of the cocrystals was enhanced by the optimized batch, which contained an intermediate concentration of AA and was subjected to the highest temperature condition, and the data fitted well with the Higuchi model of kinetics. The stability of the cocrystals was also evaluated by accelerated stability testing to determine the percentage of drug content. Thus, cocrystallization with AA proved to be a suitable approach for enhancing the dissolution characteristics and polymorphic modification of BCS II drugs, such as EFA.