Engineering Long‐Releasing Hollow‐like or Condensed Progesterone Hormone Microcrystals with Controlled Polymorphism

Progesterone is an endogenous steroid hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. Progesterone crystallization techniques have previously reported. Among these techniques, solvent crystallization and different solvent:anti‐solvent systems are considered. Herein, the selective development of either hollow‐like or condensed progesterone microcrystals in elevated yield with controlled polymorphism, habit, and release is described for the first time. For the hollow microcrystals, isopropyl alcohol (IPA) and double‐deionized water (DDW) system is developed as solvent:anti‐solvent, while acetonitrile (AcN) and DDW system are developed for the condensed microcrystals. The microcrystals obtained from both developed crystallization systems are thoroughly investigated with varied microscopic techniques, including brightfield and scanning electron microscopy (SEM), thermal analysis by differential scanning calorimetry (DSC), and crystallography by powder X‐ray diffraction (PXRD) and single XRD, and have been compared. Results show that the crystals of the IPA:DDW crystallization system are hollow and exhibit several habits, whereas the microcrystals of the AcN:DDW crystallization system are more condensed. However, both systems are found to have a wide crystal size distribution of one stable polymorph and are thus highly useful for tunable release. More importantly, these microcrystals exhibit elongated and slow release for 14 days under an expedited release conditions model, indicating suitability for long‐term and potential localized release applications.