The kinetics and mechanism of structural collapse and crystallization of lyophilized, amorphous pharmaceutical solids.

摘要

Lyophilization, a process which is widely used to prepare stable food, biological, and pharmaceutical products, often results in the formation of amorphous solids. Amorphous solids are known to undergo structural collapse and subsequent crystallization during processing and/or storage. While collapse and crystallization have been characterized for amorphous polymeric materials, these phenomena are not well described for lyophilized pharmaceutical compounds.; Utilizing crystallization data obtained from thermal and microscopic analyses, collapse of lyophilized, amorphous sucrose and procainamide hydrochloride was observed to follow the collapse mechanism proposed for polymers by Levine and Slade, which is based upon the Williams, Landel, and Ferry free volume theory.; The mechanism of crystallization was elucidated by both kinetic analysis of the thermal data using the Avrami-Erofe'ev and Prout-Tompkins equations, and by microscopic analysis. The effects of moisture on collapse and crystallization were also investigated. The results of this work suggest a wide range of practical applications within the pharmaceutical industry.