Using Raman to Track API and Solid Dosage Forms During Drug Development

This quick, one-time registration gives you access to members-only site benefits. Many pharmaceutical quality programs fail to account for the fact that API forms can change during drug development. They may be the same compound, chemically, but have different particle sizes or morphologies. In tableting or encapsulation, this fact can lead to processing problems — for example, when an API particle that was spherical early on in the development process becomes rod-shaped later on, then causes agglomeration problems during blending. Worse yet, differences in form can also result in quality problems or adverse reactions in patients. This is especially important in crystallization, since different forms or polymorphs of the same compound may have vastly different properties — different solubilities, dissolution rates, stabilities or bioavailabilities. As G. McGeorge has written, “FDA expects that [any] crystallization process is in control and that the polymorph generated will provide predictable properties in-vivo.” [1]. Both NIR and Raman spectroscopy are being used to study and monitor API forms during development to understand, correct and improve processes, facilitate continuous processing and improve quality. This brief article will focus on Raman and its use in detecting crystal polymorphs during API development, as well as its use in tableting. It will summarize how the technology is being used, describe the benefits it offers and briefly compare its performance with NIR. Stimulating more interest in Raman spectroscopy is the fact that the systems have become much easier to operate over the years, and the technique offers such benefits as flexible sampling, including the possibility of remote sampling, and confocal optics. It also allows product to be sampled through containers, and can be used with various types of samples including liquids, slurries, pastes, solids and powders. The technique also allows users to better understand the chemistry of the process being