Impact of Crystallization Engineering in the Pharmaceutical Industry

Abstract:

In the pharmaceutical industry the synthetic construction of the active pharmaceutical ingredient (API) involves many steps from forming intermediates to the final API reaction. One of the last critical steps is the crystallization and particle size/morphology treatment of the API. The method of crystallization is important to ensure that the correct crystal form, desired purity and desired yield are achieved prior to formulating the API into a drug product. In many cases the API morphology or particle size needs to be modified to aid in downstream formulation processing, to help improve the API bioavailability or to improve the filterability of the API during isolation. For a chemical engineer, the challenge is to design a crystallization and particle engineering strategy to form particles that are acceptable in process scale-up and for downstream formulation processing.

The focus of this presentation is to demonstrate various engineering methods to physically alter the morphology or particle size of API compounds during or after crystallization. For instance, API particles that are needle shaped can be altered to form block or brick shaped particles that result in improved powder handling. For other cases, the particle size of the API can be reduced by strategic seeding, wet milling or dry milling to aid in bioavailability for low solubility compounds or to help improve content uniformity for formulations with low drug loadings. Also, particle engineering methods to grow or agglomerate particles can be used to overcome API filtration issues. The engineering approaches to overcome each of these issues will be presented and will demonstrate the impact of engineering practice in the pharmaceutical industry.