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Crystal growth of progesterone metastable and stable polymorphs by polymer induced herteronucleation (PIHn) method
Authors:Andrea Mariela Araya‐Sibaja  Valdir Soldi  Carlos Eduardo Maduro de Campos  Simone Gonalves Cardoso  Silvia Lucia Cuffini
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 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.
Keywords:crystal growth  progesterone polymorphs  polymer‐induced heteronucleation  stability study
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