Improving the Stability, Dissolution, and Bioavailability of Isotretinoin by Cocrystallization

Abstract

Isotretinoin (13-cis retinoic acid, ITT) is a gold standard therapy for the treatment of severe acne. However, because of its poor absorption, ITT must be taken with fatty meals to increase bioavailability. The coadministration of food could reduce the compliance of patients and increase the risk of inconsistent serum levels because of different eating habits. In this work, we designed and synthesized four cocrystals of ITT. The cocrystal between ITT and ethyl nicotinate (ENT), namely, ITT-ENT, presented better chemical stability, dissolution, and absorption than ITT itself. The AUC0–10h of ITT-ENT cocrystal capsules is 2.6 times as that of the commercially available ITT capsules in the fasted state. Because of the high bioavailability in the fasted state, the food has a marginal effect on the absorption of cocrystal capsules. This work sets a good example for applying cocrystal technology to enhance the absorption and mitigate the food effect of drugs.