Crystallization of Organic Compounds, 2nd Edition

Chapter 12Drying

12.1 INTRODUCTION

Drying is a unit operation which follows filtration. The primary objectives of the drying operation is removal of solvents from the wet cake to meet specifications in the dry solid.

In the case of active pharmaceutical ingredient (API), the acceptable levels of residual solvent may be set according to safety (solvent toxicity), regulatory, or stability requirements, similar to those specifications of chemical impurities. The level of residual solvents may affect drug–excipient interaction and can have impact on final drug product properties and performance. For API intermediates, these specifications may be set according to the tolerance of solvents in the subsequent chemistry steps.

Another key objective of drying is to achieve or maintain the desired crystal form and particle size distribution obtained by crystallization. The desired form, which can be a solvate or hydrate, may be produced during crystallization, and it is important to keep the desired crystal form during the drying operation. In some cases, the desired form may not be the crystal forms generated during the crystallization and is more practical to generate the desired form via the drying operation. Needless to say, it is desirable to generate nicely flowable solid powder of uniform particle size distribution with minimum particle attrition and formation of agglomerates after drying.

From the fundamental mechanism perspective, drying is a complex distillation carried out ...