Investigation on polymorphic behavior of progesterone and stabilization by co-crystallization: a review

Progesterone, extensively used in human as well as veterinary medicines is a progestogen type of hormone. With the aim for hunting the stable polymorph, this review examines polymorphic behavior of progesterone and stabilization of less stable form by co-crystallization. An overview of two monotropically related forms of progesterone--form-I and form-II, synthetic enantiomer, ent-progesterone and racemic progesterone is provided. Different methods reported in the literature for the formation of polymorphs of progesterone are discussed here. After extensive manual screening it has been found that, though there are few methods mentioned in the literature for the formation of form-II, there is a lack of reproducibility in the recipes. This contribution also briefly reviews three other forms of progesterone (form-III, form-IV and form-V) which appear only in equilibrium melt and cannot be structurally characterized. Finally, comparison of different physical properties of form-I and form-II are also addressed.