Studies on Methods of Particle Size Reduction of Medicinal Compounds. VIII. Size Reduction by Freeze-Drying and the Influence of Pharmaceutical Adjuvants on the Micromeritic Properties of Freeze-Dried Powders

Abstract

The size reduction of solid drugs was attempted utilizing the freeze-drying of a two-component system comprising a solute and a solvent. It was found that the concentration of the drug to be frozen greatly influenced the average particle size of the resulting powder. The component of a system which forms a hydrate or a solvate produced more finely divided particles than did that of a simple eutectic system. This can be attributed to the effect of the peritectic reaction in the process. As the griseofulvin and benzene system gives a phase diagram with an incongruent melting point and forms a 1 : 2 solvate, the average particle size of the freeze-dried powder could be reduced to the submicron level. On the addition of surfactants to this system, micronized particles were obtained and the dissolution rate of griseofulvin was improved considerably.