Crystallization of progesterone polymorphs using polymer-induced heteronucleation (PIHn) method.
Progesterone is a natural hormone steroid used in humans for several treatments and in livestock for artificial insemination, which exhibits two polymorphic forms at ambient conditions: form 1 and form 2. Form 2 is metastable and more soluble than form 1; however, it is not suitable to use as powder raw material because it transforms into form 1 by the effects of grinding. A polymorphic screening of progesterone based on polymer-induced heteronucleation method was performed as an alternative to prepare the metastable form. Polyvinyl alcohol, hydroxypropyl methylcellulose (HPMC), dextran, gelatin, polyisoprene (PI) and acrylonitrile-butadiene (NBR) copolymer were used. Crystals were prepared from 0.5, 10 and 40 mg/mL solutions in acetone at room temperature by solvent evaporation. The samples were characterized by X-ray powder diffraction, differential scanning calorimetry (DSC), scanning electron microcopy and attenuated total reflectance infrared Fourier transform spectroscopy. Form 1 was nucleated from 40 mg/mL solutions on the six polymers and from 10 mg/mL solutions on PI and NBR. The mixture of form 1 and form 2 was obtained from 10 mg/mL solution on HPMC, dextran and gelatin and from 0.5 mg/mL solution crystallizations. Therefore, the polymeric devices, which crystallized the metastable and more soluble polymorph (2) of progesterone, would be a promissory alternative for the pharmaceutical applications.
Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina , Florianópolis , Brasil .
Andrea Mariela
AM
Araya-Sibaja
Valdir
V
Soldi
Carlos Eduardo Maduro
CE
Campos
Simone Gonçalves
SG
Cardoso
Silvia Lucia
SL
Cuffini
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004355:Drug Stability; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry*; D011374:Progesterone / Q000737:chemistry*; D011372:Progestins / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D011108:Polymers; D011372:Progestins; D011374:Progesterone
Growth from solutions; polymer templating; polymer-induced heteronucleation; polymorph screening; preferred orientation; progesterone