Virtual screening of coformers and solubility test for glibenclamide cocrystallization

Abstract

Background: The therapeutic effectiveness of active pharmaceutical ingredients (API) depends on their solubility. API, which has poorly soluble drugs, can cause low bioavailability. According to the biopharmaceutical classification system (BCS), glibenclamide is classified under BCS Class II drugs), which has low solubility and high permeability. Cocrystallization is one method to enhance the physical properties of drugs, especially the solubility. Aims and Objectives: In this study, we apply the approach to the solid state to estimate the probability of cocrystal formation using virtual screening, and then, study the solubility and dissolution test of one of the best coformers. Materials and Methods: We used virtual screening of coformers for glibenclamide by employing the molecular docking method. AutoDock was used for docking, and the type and energy (Ei) of interaction were observed. The work was continued by the cocrystallization process using dry grinding. Solubility and dissolution tests have referred to the Higuchi and Connor methods using the ultraviolet spectrophotometer. Results: Based on molecular docking, the best of three from coformers were oxalic acid (Ei = −1.6 kcal/mol), benzoic acid (Ei = −2.6 kcal/mol), and ascorbic acid (Ei = −2.1 kcal/mol). The result of the solubility test showed that glibenclamide oxalic acid increases by 81.6% compared to pure glibenclamide at 24 h. The result of the dissolution test showed that glibenclamide oxalic acid has a better curve (77.3% in 60 min) that pures glibenclamide (44.52% in 60 min). Conclusion: This study indicated that oxalic acid as a coformer can increase the dissolution profile of glibenclamide by the approach cocrystalization method.