Abstract
The present investigation aims to develop novel curcumin-ascorbic acid cocrystal for enhancing the solubility, stability, and complementary biological activities for curcumin. Based on in silico approach to screen ascorbic acid as a coformer for curcumin, cocrystals were prepared by the solvent evaporation method, and further evaluated for saturation solubility, cocrystal propensity, physicochemical interactions (FTIR and DSC), XRD, drug dissolution, etc. In silico findings confirmed the suitability (H_ex, G_mix) of ascorbic acid for the cocrystallization of curcumin. The DSC and XRD data of the solvent evaporated curcumin-ascorbic acid mixture confirmed the formation of cocrystal, eutectic, and binary mixture with an excess of coformer. The binary phase diagram implied 0.5 to the 0.65-mole fraction of curcumin, essential for cocrystallization with ascorbic acid. The novel curcumin ascorbic acid cocrystals revealed extraordinary improvement in aqueous solubility of curcumin, especially, 576 fold in distilled water, 10 fold in the buffer pH 1.2, and 9 fold in the buffer pH 6.8. The curcumin-ascorbic acid cocrystal system exhibited a superior dissolution profile compared to neat curcumin. Thus, ascorbic acid has enunciated its role as a coformer for curcumin in cocrystal formation, which has been complemented by predicted complementary biological activities, and stability (acidic milieu).
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