Modeling and monitoring of polymorphic transformations during the drying phase of wet granulation

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 alpha-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.