Drug–Drug Cocrystals Provide Significant Improvements of Drug Properties in Treatment with Progesterone

Abstract

Progesterone (Prog), a natural steroid hormone, is widely used in birth control pills and menopausal hormone replacement therapies. Phloroglucinol (SPF) and resveratrol (RSV) are also two kinds of active products that can be used during pregnancy. Drug–drug cocrystals of Prog with SPF and RSV were designed and successfully synthesized for purpose of bringing improvements of drug properties, including solubility, hydroscopic stability, and color stability. The cocrystals and their hydrate structures were systematically characterized by X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. In addition, powder dissolution experiments of Prog, Prog-SPF, and Prog-RSV were conducted in aqueous solutions with the presence of different surfactants, and the result revealed that the Prog-SPF cocrystal exhibits a superior solubility compared with Prog and Prog-RSV. Furthermore, the Prog-SPF cocrystal also enhances the hydroscopic stability and color stability of SPF. Those findings may provide a promising formulation to overcome some weaknesses of the parent drugs.