Rapid precipitation of biochemicals

Abstract

The production of uniform fine crystalline particles is highly desirable for pharmaceutical products in order to enhance stability and dissolution rates and, thereby, to favour high bioavailability. Precipitation under high-supersaturation conditions favours nucleation over growth processes and will result in smaller particles. Little fundamental information is available on the kinetics of nucleation and growth of organic compounds when precipitated under high-supersaturation conditions by the addition of a non-solvent. In order to accurately measure such rapid kinetics a technique for rapid mixing prior to any nucleation events is required. The authors report the use of a grid mixing device with a mixing time of less than 3 ms to measure the nucleation and growth rates of L-asparagine and lovastatin when precipitated by non-solvents at high supersaturation ratios. Nucleation induction times as small as 60 ms are observed, and the growth of asparagine at high supersaturation is found to be described by the same rate law as previously determined at low supersaturations.