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Modeling and Monitoring of Polymorphic Transformations During the Drying Phase of Wet Granulation

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Abstract

Purpose. The purpose of this work was to monitor polymorphic transformations of glycine during the drying phase of a wet granulation and model the polymorphic conversions using a time-based reconciliation model.

Methods. Near-infrared spectroscopy (NIR) was used for quantitation of polymorphs, and X-ray powder diffraction (XRPD) was used for qualitative analysis of polymorphs.

Results. The data show that the faster the granulation was dried, the more kinetic trapping of the metastable α-glycine polymorph, as predicted by reconciliation of the time scales of both the drying rate and the rate of the solution-mediated conversion.

Conclusions. By knowing basic properties of the drug substance (solubility of the polymorphic forms and the rate of the solution-mediated conversion), processing conditions, such as the drying rate, can be adjusted to anticipate and prevent potential polymorphic transformations.

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Author notes

  1. Tiffani D. Davis

    Present address: Eli Lilly and Company, Indianapolis, Indiana, 46285

Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, 48908-2091

    Tiffani D. Davis, Garnet E. Peck, Joseph G. Stowell, Kenneth R. Morris & Stephen R. Byrn

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  1. Tiffani D. Davis
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  2. Garnet E. Peck
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  3. Joseph G. Stowell
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  4. Kenneth R. Morris
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  5. Stephen R. Byrn
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Correspondence to Kenneth R. Morris.

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Davis, T.D., Peck, G.E., Stowell, J.G. et al. Modeling and Monitoring of Polymorphic Transformations During the Drying Phase of Wet Granulation. Pharm Res 21, 860–866 (2004). https://doi.org/10.1023/B:PHAM.0000026440.00508.cf

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