VIRTUAL SCREENING OF COFORMERS FOR ATORVASTATIN Co-CRYSTALLIZATION AND THE CHARACTERIZATIONS OF THE Co-CRYSTALS

摘要

Atorvastatin calcium (ATC) is very slightly soluble in water and it is classified under BCS class II drugs. A widely used method to enhance the solubility of drugs is co-crystallization. In this work, we screened six co-formers for ATC by employing molecular docking method. The work was continued by co-crystallization process using slurry method, solubility assay of the mixtures using HPLC, and characterization of the co-crystal by PXRD, DSC and SEM. Based on molecular docking, the best co-former is aspartame (Ei = -4.70 kcal/mol). The docking result fits the solubility assay of the ATC-aspartame co-crystal (136.77% increasing of solubility compared to ATC). ATC-aspartame co-crystal shows better dissolution profile (91.62 % in 60 minutes) than ATC (73.54 % in 60 minutes). The characteristic peaks of ATC and aspartame were gone, whilst new peaks appeared after slurry process. The ATC-aspartame characterization by PXRD, DSC and SEM positively confirmed that the co-crystallization of ATC-aspartame using slurry method was successful.