title: Dissolution properties, solid-state transformation and polymorphic crystallization: progesterone case study.
abstract: Progesterone is a natural steroid hormone and a poor soluble drug which presents two polymorphs (forms 1 and 2). Different methods to obtain form 2 were tested and a complete solid-state characterization of both polymorphs (forms 1 and 2) was conducted. X-ray powder diffraction, hot stage microscopy, Fourier transform infrared, dispersive Raman, (13)C solid-state nuclear magnetic resonance spectroscopy, thermal analysis, scanning electron microscopy techniques and intrinsic dissolution rates (IDR) were applied to investigate physical-chemical and dissolution properties of these two polymorphs. Form 2 was obtained from diluted solutions and from melting after cooling at room temperature. Form 1 was obtained from concentrated solutions and, a mixture of both polymorphs was crystallized from intermediate solutions. The crystal habit was not a distinctive characteristic of each polymorph. The effect of mechanical stress was evaluated in the metastable polymorph (form 2). We observed that grinding form 2 produced seeds of form 1 that induced the transformation of form 2 into form 1 at high temperature. The polymorphic quantification from XRD patterns of ground samples were carried out by the Rietveld method. After grinding and at room temperature conditions (∼25 °C), it was observed the transformation of 17% of form 2 into form 1 in 10 days.
authors.affiliation: Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina , Florianópolis , Brasil .
authors.forename: Andrea Mariela
authors.initials: AM
authors.lastname: Araya-Sibaja
authors.forename: Amarilis Scremin
authors.initials: AS
authors.lastname: Paulino
authors.forename: Gabriela Schneider
authors.initials: GS
authors.lastname: Rauber
authors.forename: Carlos Eduardo Maduro
authors.initials: CE
authors.lastname: Campos
authors.forename: Simone Gonçalves
authors.initials: SG
authors.lastname: Cardoso
authors.forename: Gustavo Alberto
authors.initials: GA
authors.lastname: Monti
authors.forename: Valeria
authors.initials: V
authors.lastname: Heredia
authors.forename: Ismael
authors.initials: I
authors.lastname: Bianco
authors.forename: Dante
authors.initials: D
authors.lastname: Beltrano
authors.forename: Silvia Lucia
authors.initials: SL
authors.lastname: Cuffini
mesh_terms: D003460:Crystallization; D009682:Magnetic Resonance Spectroscopy; D033362:Powder Diffraction; D011374:Progesterone / Q000737:chemistry*; D011372:Progestins / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
chemical_list: D011372:Progestins; D011374:Progesterone