Wet granulation and drying: Monitoring and control

Tiffani Deanne Davis, Purdue University

Abstract

The objectives of this project were to both model and monitor the properties of the wet mass, specifically for polymorph content and moisture content. While the wet granulation process is an important technique in the production of pharmaceuticals, both the addition of solvent and subsequent drying can result in unanticipated and/or undesired polymorphic changes. The hypothesis tested for the polymorphism studies is that the extent of polymorphic conversion during each phase of a granulation will depend on the time scales of the pharmaceutical process in relation to the time scale (i.e. kinetics) of the phase change. In other words, transformations during the wetting process will depend on both the kinetics of the solution mediated conversion as well as the time scale of the wetting phase of the granulation. Transformations during drying will depend on the kinetics of both the solution mediated conversion and drying. Online X-ray powder diffraction was used to monitor and develop a model for polymorphic transformations during wetting. The utility of the developed model lies in its potential to predict the length of granulation time required for a specified amount of polymorphic transformation. Transformations during drying were modeled and monitored using offline near-infrared spectroscopy (NIR). This model demonstrates that both the drying rate and the solution mediated conversion rate will dictate the extent of polymorphic conversion. The hypothesis tested for the fast drying method is that during the heat transfer limited portion of the drying profile, the inlet temperature may be increased far above the melting point of the active ingredient without raising the bed temperature. Thus, the drying will be safely accelerated both for moisture labile compounds and for compounds with excessively long drying phases. Online NIR was used to monitor the moisture content during the fluid bed drying process, and elucidated the drying mechanisms that enabled the fluid-bed drying process to be modeled and the fast drying technique to be implemented.

Degree

Ph.D.

Advisors

Byrn, Purdue University.

Subject Area

Pharmaceuticals|Pharmacology

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