(758d) PAT for Form Monitoring during Drying

Dimitri, M., Teva

PAT for Form Monitoring During Drying

M. Dimitri, S. Allwein, P. Mudipalli, and M. Christie

Teva Branded Pharmaceuticals, Inc.

Chemical Synthesis Center

383 Phoenixville Pike

Malvern, PA 19355

A.I.Ch.E. Annual Meeting 2015

Session: “PAT for Process Understanding and Elucidation of Fundamental Phenomena in Drug Product/Substance Development”

Abstract:  Controlling and monitoring polymorphic form during drying of active pharmaceutical ingredients (APIs) is increasingly an area of interest particularly for specialized drying, such as humidified drying. The use of PAT instruments is often powerful in understanding the drying kinetics of an API, identification of the final polymorphic form in situ in the dryer, and determination of drying end point. This study examines the development and use of Raman Phat Probe technology to monitor a humidified drying process of an API and examines some of the key scale-up parameters involved. For this API, three different known polymorphs are possible during drying, with one polymorph being irreversible once formed. In addition, online analysis was determined to be critical as the API is extremely sensitive to relative humidity and form conversion occurs rapidly, making offline analysis challenging. This study demonstrates the use of raw spectra and chemometric analysis in monitoring and defining the drying kinetics of the two main forms of interest. The example of the use of this technology that is being presented shows its applicability both for drying process development and for confirmation of form at scale (ie, in situ in the dryer).

Keywords: Drying, Phat Raman, Form Monitoring, PAT