Crystallization of Organic Compounds, 2nd Edition

Chapter 13Special Applications

13.1 INTRODUCTION

While solution crystallization is the main focus of this book, there are applications which are special cases of the crystallization methods described in earlier chapters. For example, a process requiring sterile crystallization is a special example of an antisolvent addition and is presented in Example 13.1. In this particular example, it is necessary to produce fine particles in order to meet drug dissolution time specifications in the final single‐dose vials. Furthermore, the material is thermally unstable. Therefore, special precautions have to be taken to minimize any degradation during processing.

Integration of crystallization with other process operations, specifically reaction, is another aspect of crystallization that has significant potential to improve overall process economics. In Examples 13.2 and 13.3, two cases are presented in which products are selectively crystallized during reaction. As a result, reaction selectivity, yield, and the cost of raw materials are significantly improved. Furthermore, solvent recovery is simplified since the same solvent is used in both reaction and crystallization. This type of operation can provide significant improvement in process economics and should be part of the development of crystallization processes when applicable.

Other crystallization techniques that are less frequently applied in the pharmaceutical industry, such as melt and freeze crystallization, may be applicable ...