Preparation of sterile long-acting injectable medroxyprogesterone acetate microcrystals based on anti-solvent precipitation and crystal habit control.

Abstract:

:Background: 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. Methods: 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). Results: All these crystals were proved to be of the same crystal form with different preferential growth orientation by PXRD, DSC, and SEM. The in vitro 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. Conclusions: 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.

journal_name

Expert Opin Drug Deliv

authors

Sun R,Guo Y,Yin N,Yin J,Yin T,He H,Gou J,Zhang Y,Tang X

doi

10.1080/17425247.2019.1662394

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

1133-1144

issue

10

eissn

1742-5247

issn

1744-7593

journal_volume

16

pub_type

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