Effect of jet velocity on crystal size distribution from antisolvent and cooling crystallizations in a dual impinging jet mixer

Abstract

In the pharmaceutical industry, good control of the crystal size distribution (CSD) can improve process efficiency and formulation of the drug product. An effective method to continuously generate small crystals of narrow size distribution for some drug/solvent systems is by using a dual-impinging jet (DIJ) mixer. This paper demonstrates the first use of a DIJ mixer combining cooling and antisolvent crystallization to generate crystals with a typical pharmaceutical solubility. In a confined Y-shaped DIJ mixer by this approach, product crystals are obtained with smaller sizes and aspect ratios than a conventional batch process. We also quantify the relationships between the particle size, distribution width, and distribution modality on the inlet jet velocity. This combination of cooling and antisolvent crystallization may widen the application of DIJ mixers for the generation of small uniform pharmaceutical crystals.