Preparation and pharmacokinetics study of albumin-coated crystalline progesterone long-acting microcapsules for injection

Progesterone spherical crystals (PSCs) were prepared by emulsion-like solvent diffusion (QESD), and then human serum albumin (HSA) was wrapped on the outer surface of PSCs by spray drying technique to prepare albumin-coated progesterone spherical crystal microcapsules with high drug loading capacity (PH-MCs). The appearance morphology, particle size, size distribution, and in vitro release of PSCs were used as indicators to screen the emulsifier types and concentration, the types of good solvent, and the temperature difference between organic and aqueous phases to determine the prescription process of PH-MCs. The results showed that the bioavailability of PH-MCs was 1.66 times higher than that of the same dose of commercially available oil solution, and there was no significant burst release. The microcapsules were able to satisfy a one-week sustained drug release in vivo (higher than the therapeutic dose of 5 ng). The stimulatory properties of intramuscular progesterone microcapsules were studied on SD rats by foot-licking test and hematoxylin-eosin (H&E) staining. The results showed that PH-MCs were significantly less irritating at the injection site compared to the commercially available progesterone oil solution, indicating that PH-MCs are biocompatible with muscle tissue.