cg5b00699_si_002.cif (18.8 kB)

Lenalidomide–Gallic Acid Cocrystals with Constant High Solubility

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posted on 07.10.2015 by Jia-Xi Song, Jia-Mei Chen, Tong-Bu Lu
Pharmaceutical cocrystals are an efficient approach to improve the solubility of insoluble active pharmaceutical ingredients (APIs), while the dissolution profiles of pharmaceutical cocrystals usually exhibit a type of “spring and rapid parachute” effect that influences stability and pharmacodynamic sustainability, in which the high apparent solubility induced by the formation of cocrystals can only be maintained for a short time (usually minutes) in the metastable zone and then decreases rapidly afterwords. Herein we reported the preparation and structures of two lenalidomide cocrystals with gallic acid (1, 2). After the formation of cocrystals, the intrinsic dissolution rate and apparent solubility of lenalidomide were found to be enhanced. The high solubility of cocrystals can keep for 48 h without dropping. The result of phase solubility study indicates gallic acid (GA) forms a 1:1 complex with lenalidomide (Rev) in aqueous solution, with a stability constant of 1713.2 L/mol. The multiple hydrogen bonding interactions between GA and Rev are attributed to the formation of GA-Rev complex in aqueous solution and subsequently the constant high solubility of cocrystals.