Solubility and dissolution rate of progesterone cocrystals using 4-fluorobenzoic acid and 2-hydroxy-6-naphthoic acid as coformers

• Improve the solubility and consequently enhance the oral bioavailability of progesterone (P). • Use a suitable co-former to convert the parent compound progesterone into a co-crystal. • Using solution crystallization technology in the stoichiometric ratio of 1: 4 and 1: 2. • The results show that the co-crystal can improve the solubility of progesterone in water. • Pharmaceutical cocrystal can solve the problem of poorly soluble APIs. The objective of our study was to improve the solubility and consequently enhance the oral bioavailability of progesterone, an endogenous steroid with poor water solubility, by synthesizing cocrystals. Progesterone cocrystals with pharmaceutically acceptable conformers, namely, 4-fluorobenzoic acid and 2-hydroxy-6-naphthoic acid, in a stoichiometric ratio of 1:4 and 1:2, respectively, were synthesized using solution crystallization technology. The cocrystals were characterized using single-crystal X-ray diffraction, powder X-ray diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetry. Results from the solubility and dissolution experiments indicated that the solubility of both progesterone cocrystals in water and dissolution rate in 0.1 M HCl solution (pH = 1) could enhance the aqueous solubility of progesterone 1.93 and 1.12 times, respectively. Therefore, the formulation of pharmaceutical cocrystals is a potentially viable and effective approach to improve the solubility of active pharmaceutical ingredients that are poorly water soluble.