Progesterone long-acting injection for assisted reproduction: Formulation and in vivo pharmacokinetic behavior

Abstract

Abstract Progesterone (PG) is a key hormone that maintains the normal physiology of female reproductive system. However, due to its insolubility, the drugs used for assisted reproduction in clinical are mainly oil injections, patients with multiple injections are prone to adverse reactions such as redness, pain, induration and even muscle necrosis. In this study, we developed the progesterone long-acting injection which was administered every 7 days and could substantially reduce injection-site adverse reactions after long term administration. The progesterone long-acting injection containing 20% (w/v) progesterone was first prepared using solvent–antisolvent precipitation method. The particle size, X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and in vitro dissolution were carried out to evaluate the characteristics. The results showed that the particle size of the progesterone long-acting injection was Dv10 8.128µm, Dv50 15.457µm, DV90 26.942µm and the crystal form was form α. In addition, the physical stability was also investigated after storage for 6 months at 40℃ and no obvious change in particle size was observed and the sample resuspension was well, indicating that the selected formulation was reasonable. The in vivo toxicology studies and pharmacokinetics tests showed that the progesterone long-acting injection had lower irritation than progesterone oil injection and could achieve sustained release for 7 days with a flat trend in plasma concentrations. Therefore, it was obvious that the progesterone long-acting injection we designed exhibited a lower muscle irritation and longer release period, which could be a better dosage form than progesterone oil injection and significantly increase patient compliance.