Crystal growth of progesterone metastable and stable polymorphs by polymer induced herteronucleation (PIHn) method

The selective crystallization of progesterone polymorphs prepared by Polymer‐Induced Heteronucleation (PIHn) method was investigated. Polyvinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), dextran, gelatin, polyisoprene (PI), and acrylonitrile/butadiene copolymer (NBR) were used as heteronucleants. Crystallizations were conducted from 0.5, 10 and 40 mg mL −1 solutions in chloroform at room temperature by solvent evaporation. The samples were characterized by X‐ray powder diffraction, differential scanning calorimetry, infrared spectroscopy and scanning electron microscopy. Form 2 was obtained from 0.5 mg mL −1 solution in almost all polymers. A mixture of both polymorphs crystallized from the three concentrations on gelatine; from 10 and 40mg mL −1 on PVA and HPMC and, from 10 mg mL −1 solutions on NBR. Form 2 crystallized on HPMC was stable for three months under ambient stress conditions (40ºC and 75% RH). These results are good evidence that the tailoring of new formulations and devices with progesterone the metastable and more soluble form 2 is possible.