Crystallization of Organic Compounds, 2nd Edition

Chapter 1Introduction to Crystallization

Crystallization has been the most important separation and purification process in the pharmaceutical industry throughout its history. Many parallels exist in the fine chemicals industry as well. Over the past several decades, the study of crystallization operations has taken on even higher levels of importance, because of several critical factors that require increased control of the crystallization process. These levels of control require better understanding of the fundamentals as well as of the operating characteristics of crystallization equipment, including the critical issue of scale‐up.

In the pharmaceutical industry, the issue of better control, desirable in and of itself, is reinforced by the need to satisfy the regulatory authorities that a continuing supply of active pharmaceutical ingredients (APIs) of high and reproducible quality and bioavailability can be delivered for formulation and finally to the patient. The “product image” (properties, purity, etc.) of this medicine must be the same as that used in the clinical testing carried out to prove the product’s place in the therapeutic marketplace. Some additional comments on critical issues, quality‐by‐design, and regulatory issues are included later in this chapter (Section 1.4).

The issues noted above that require increased control, relative to previous practice, include the following:

• Final bulk drug substances must be purified to high levels that are increasingly quantifiable ...