Preparation and characterization of efavirenz cocrystals: An endeavor to improve the physicochemical parameters

Abstract

Cocrystallization technique has gained increasing interest due to its ability to modify the physicochemical properties of a drug substance. Efavirenz comes under biopharmaceutical classification system class II compounds that denote the low solubility and high permeability nature of the drug. Thus, the main aim of this study is to develop efavirenz cocrystals using different coformers other than previously reported to enhance the dissolution behavior and solubility of efavirenz. Further, to draw a meaningful conclusion about selecting the coformers to synthesize the cocrystals. The cocrystals of efavirenz with four different water soluble coformers such as DL-alanine, oxalic acid, maleic acid, and nicotinamide (1:1 molar ratio) were prepared using slow solvent evaporation strategy. The cocrystals characterization was done using FT-IR, DSC, PXRD and SEM. Further, the stability, solubility and dissolution studies were performed along with fitting the dissolution data into kinetic models. The FT-IR data revealed the negligible shift in –C=O and –N-H/-O-H stretching frequencies in prepared cocrystals compared to a pure drug. However, the thermal behavior of prepared cocrystals showed the strong interactions between pure drug and coformers indicating the existence of hydrogen bond between drug and coformer. The PXRD patterns of cocrystals indicated different 2ϴ values compared to their starting materials. Although all the coformers are water soluble, the increased dissolution profile was seen only for efavirenz-DL-alanine and efavirenz-oxalic acid cocrystal, whereas efavirenz-maleic acid and efavirenz-nicotinamide cocrystals exhibited decreased dissolution compared to pure efavirenz. Nevertheless, the cocrystals were found to be stable for at least six months in ambient conditions. This concludes that cocrystallization is an apt strategy to improve the physicochemical properties of an active pharmaceutical ingredient only with suitable coformers.