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: Research - peer-reviewArticle

    • 125 Citations

    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.

    LanguageEnglish (US)
    Pages391-395
    Number of pages5
    JournalOrganic Process Research and Development
    Volume4
    Issue number5
    StatePublished - Sep 2000

    Profile

    Progesterone
    Raman spectroscopy
    Raman Spectrum Analysis
    phase transformations
    Phase transitions
    Monitoring
    solid phases
    heat measurement
    infrared spectroscopy
    scanning
    liquids
    diffraction
    x rays
    temperature
    Phase behavior
    Crystallization
    Differential scanning calorimetry
    Infrared spectroscopy
    Suspensions
    Crystalline materials

    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: Research - peer-reviewArticle

    @article{8f590bb8c7a34d16b26337bc09cbb4e6,
    title = "An investigation of solvent-mediated polymorphic transformation of progesterone using in situ Raman spectroscopy",
    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.",
    author = "Fang Wang and Wachter, {John A.} and Antosz, {Frederick J.} and Berglund, {Kris A.}",
    year = "2000",
    month = "9",
    volume = "4",
    pages = "391--395",
    journal = "Organic Process Research and Development",
    issn = "1083-6160",
    publisher = "American Chemical Society",
    number = "5",

    }

    TY - JOUR

    T1 - An investigation of solvent-mediated polymorphic transformation of progesterone using in situ Raman spectroscopy

    AU - Wang,Fang

    AU - Wachter,John A.

    AU - Antosz,Frederick J.

    AU - Berglund,Kris A.

    PY - 2000/9

    Y1 - 2000/9

    N2 - 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.

    AB - 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.

    UR - http://www.scopus.com/inward/record.url?scp=0034259114&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0034259114&partnerID=8YFLogxK

    M3 - Article

    VL - 4

    SP - 391

    EP - 395

    JO - Organic Process Research and Development

    T2 - Organic Process Research and Development

    JF - Organic Process Research and Development

    SN - 1083-6160

    IS - 5

    ER -