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  • Title: Progressive steps of polymorphic transformation of gabapentin polymorphs studied by hot-stage FTIR microspectroscopy.
    Author: Hsu CH, Ke WT, Lin SY.
    Journal: J Pharm Pharm Sci; 2010; 13(1):67-77. PubMed ID: 20456832.
    Abstract:
    PURPOSE: The aim of this study was to determine the progressive processes of polymorphic transformation of different gabapentin (GBP) polymorphs by using hot-stage Fourier transform infrared (FTIR) microspectroscopy. METHODS: Four polymorphs of GBP were previously prepared and then identified by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, FTIR microspectroscopy and X-ray powder diffractometry. A novel hot-stage FTIR microspectroscopic technique was used to investigate the progressive steps of polymorphic transformation of each GBP polymorph sealed within two pieces of KBr plates. RESULTS: Four polymorphs (Forms I, II, III and IV) of GBP were well characterized. The GBP form I was proven to be a monohydrate, but other GBP forms II-IV were anhydrous. Different thermal-induced progressive processes and steps of polymorphic interconversion of GBP polymorphs were clearly found from the changes in the three-dimensional IR spectral contour and peak intensity by using hot-stage FTIR microspectroscopy. The results also indicate that GBP form I was dehydrated and transformed to form III, and then converted to form IV; whereas GBP forms II and III directly transformed to form IV during heating. The GBP form IV was the last polymorph before the intramolecular lactamization of GBP. CONCLUSION: A one-step novel hot-stage FTIR microspectroscopy was successfully applied to simultaneously and continuously investigate the progressive processes and steps of thermal-induced polymorphic interconversion of GBP polymorph in the solid state.
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