Preparation of sterile long-acting injectable medroxyprogesterone acetate microcrystals based on anti-solvent precipitation and crystal habit control Rong Sun Yuting Guo Na Yin Jiaojiao Yin Tian Yin Haibing He Jingxin Gou Yu Zhang Xing Tang 10.6084/m9.figshare.9851969.v1 https://tandf.figshare.com/articles/journal_contribution/Preparation_of_sterile_long-acting_injectable_medroxyprogesterone_acetate_microcrystals_based_on_anti-solvent_precipitation_and_crystal_habit_control/9851969 <p><b>Background</b>: To overcome the rigorous aseptic process widely adopted by commercial long-acting injections, this work aimed to prepare a sterile MPA injection by manipulating the crystal habit through a bottom-up method.</p> <p><b>Methods</b>: The habit of the precipitated crystals was modified by changing the process conditions. Wherein, the cubic crystal (MPA-C) was obtained by mixing acetonitrile and water at a ratio of 1:4 (v/v) under an ultrasonic condition. Spherical crystal (MPA-S) was prepared with acetonitrile-water mixture (1:20, v/v). The addition of external additives could stop a certain crystal surface growth to obtain rod-like crystal (MPA-R) and branched crystal (MPA-B).</p> <p><b>Results</b>: All these crystals were proved to be of the same crystal form with different preferential growth orientation by PXRD, DSC, and SEM. The <i>in vitro</i> release of MPA-R microcrystal suspensions is faster than MPA-DP, while that of MPA-C is slightly slower. The relative bioavailability of MPA-C and MPA-R was 103.3% and 68.5%, respectively. The PK profile of MPA-C was most close to the commercial Depo-Provera® (MPA-DP) after intramuscular administration to male SD rats.</p> <p><b>Conclusions</b>: A cubic crystal of MPA was successfully prepared by anti-solvent precipitation method with the aid of sonication, providing an alternative strategy for the preparation of long-acting injections.</p> 2019-09-16 14:22:55 Medroxyprogesterone acetate crystal habit anti-solvent method formation mechanism