An investigation of solvent-mediated polymorphic transformation of progesterone using in situ Raman spectroscopy

Fang Wang, John A. Wachter, Frederick J. Antosz, Kris A. Berglund

    Research output: Contribution to journalArticle

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    Abstract

    Many analytical techniques, such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), infrared spectroscopy (IR) and Raman spectroscopy can be used to differentiate between crystalline polymorphs of the same chemical entity. While all of these techniques are routinely applied to off-line analysis of materials, Raman spectroscopy has the advantage over these other techniques in that Raman technology currently exists for in situ monitoring of the solid-phase behavior within a mixed suspension of liquid and solid. In this work, we present our results from an in situ Raman study, demonstrating the solvent-mediated polymorphic phase transformation of progesterone. In situ Raman analysis has shown that the appearance of Form I progesterone is always preceded by the formation of Form II progesterone. Phase transformation rates were found to increase monotonically as the temperature increases, which indicates that the polymorphic system is monotropic. Form I was found to be thermodynamically more stable than Form II, while Form II was found to be kinetically favored over Form I. The results from this study are consistent with Ostwald's law of stages and lead to an in-depth understanding of the polymorphic transformation process of progesterone. The in situ monitoring capabilities of Raman spectroscopy have allowed us to define the processing parameters required to control the morphology of crystalline progesterone.

    Original languageEnglish (US)
    Pages (from-to)391-395
    Number of pages5
    JournalOrganic Process Research and Development
    Volume4
    Issue number5
    StatePublished - Sep 2000

    Profile

    Raman spectroscopy
    Raman Spectrum Analysis
    Progesterone
    Experimental Liver Cirrhoses
    phase transformations
    Antimony Potassium Tartrate
    Butylene Glycols
    Phase transitions
    solid phases
    heat measurement
    infrared spectroscopy
    scanning
    liquids
    diffraction
    temperature
    Differential Scanning Calorimetry
    Crystallization
    X-Ray Diffraction
    Spectrum Analysis
    Technology

    ASJC Scopus subject areas

    • Organic Chemistry
    • Drug Discovery

    Cite this

    An investigation of solvent-mediated polymorphic transformation of progesterone using in situ Raman spectroscopy. / Wang, Fang; Wachter, John A.; Antosz, Frederick J.; Berglund, Kris A.

    In: Organic Process Research and Development, Vol. 4, No. 5, 09.2000, p. 391-395.

    Research output: Contribution to journalArticle

    Wang, Fang; Wachter, John A.; Antosz, Frederick J.; Berglund, Kris A. / An investigation of solvent-mediated polymorphic transformation of progesterone using in situ Raman spectroscopy.

    In: Organic Process Research and Development, Vol. 4, No. 5, 09.2000, p. 391-395.

    Research output: Contribution to journalArticle

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