Preparation of Progesterone Co-Crystals Based on Crystal Engineering Strategies

Abstract

Three co-formers of 2-chloro-4-nitroaniline (CNA), 2,5-dihydroxybenzoic acid (DHB), and 4,4′-biphenol (DOD) were selected to prepare the co-crystal of progesterone (PROG) based on crystal engineering strategies. These co-crystals were successfully obtained via slow evaporation from different solutions and were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, and differential scanning calorimetry. Different binding networks were observed in the co-crystal structures of PROG. The PROG-CNA co-crystal had the fastest rates and highest concentrations of PROG in PBS solution compared with PROG or other co-crystals in the dissolution experiments. This might be attributable to more stable and abundant interactions between the PROG and CNA molecules. Our investigations provide positive support for the selection of suitable co-formers using crystal engineering strategies.

Cocrystallization of Progesterone with Nitrogen Heterocyclic Compounds: Synthesis, Characterization, Calculation and Property Evaluation

“…By selecting CCFs with different properties, the physicochemical properties of API can be improved or designed at the molecular level without changing its structure, which is very important to maintain the biological activity of API in vivo [ 11 , 12 , 13 , 14 ]. PRO is a good substrate for cocrystallization because there are two carbonyl groups in the molecule that can act as hydrogen bond acceptors, and the steroidal parent nucleus can produce conjugation effects [ 15 , 16 , 17 , 18 ].…”