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

Abstract

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 poly morphs 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 (40 degrees C 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.