Enhanced dissolution of curcumin-resorcinol cocrystal by the inhibition effect of HPMCAS on solution-mediated phase transformation

Abstract

The present study aimed to investigate the inhibition effect of polymers on the solution-mediated phase transformation (SMPT) of cocrystals during dissolution. Curcumin-resorcinol (CUR-RES) cocrystal was prepared by slow solvent evaporation, and the best precipitation inhibitor of curcumin (CUR) was selected from five polymers including hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose (HPMC) E5, HPMC E50, Poloxamer 188 (P188) and polyethylene glycol (PEG) 6000 by solvent-shift precipitation test. Then non-sink dissolution tests and intrinsic dissolution rate (IDR) tests were performed with or without HPMCAS to explore the influence of HPMCAS on the dissolution of the cocrystal. It was showed that HPMCAS could effectively inhibit the crystallization of CUR so that the dissolved drug concentration in a predissolved 0.1 % HPMCAS solution at 2 h was nearly 15 μg/mL, which was at least 150 times higher than that without HPMCAS. The red CUR-RES cocrystal turned gradually to yellow CUR during the dissolution tests in the absence of HPMCAS, while the transformation was prevented in the presence of HPMCAS. The present work fully exploits the solubility advantages of CUR-RES cocrystal via the use of precipitation inhibitor and offers important insights into reducing the risk of SMPT during cocrystal dissolution, which is crucial for the development of pharmaceutical cocrystal formulations.