CRYSTAL SIZE AND SHAPE MEASUREMENT FOR INSITU MONITORING

Process Metrix, Llc, Pleasanton CA

Investigators

Abstract

DESCRIPTION:(Applicant's description) The long-term objective of this research is to provide an instrument for in-situ measurement of crystal size and shape so as to control and optimize pharmaceutical crystallization processes. This instrument will also be useful for research on fabrication of new crystals, especially fragile crystals. In Phase I, the investigators plan to build a prototype and test it with pharmaceutical crystals. The proposed instrument is based on laser illumination and digital imaging. The first challenge is to obtain quantitative information about crystal size and shape (imaging based techniques are generally not reliable for quantitative measurements). The investigators' approach involves using a small field of view, so as to observe a single crystal at a time. A sensor will be used to indicate the presence of a crystal in the field of view. The digital images of single crystals will be processed using a novel line integration method to obtain accurate quantitative results. Another challenge is to acquire and process data at a high enough rate to enable process control. This will be accomplished by utilizing the latest imaging technology developed for machine vision. Finally, the optical design of the instrument will account for the fact that typical crystallizers have limited viewing access. PROPOSED COMMERCIAL APPLICATION: The successful completion of Phase II will lead to a very desirable instrument for in-situ measurement of crystal size and shape during the crystal growth process. These measurements will help the user control and fine-tune the process parameters. Both size and shape are known to have a strong impact on the mechanical and thermodynamic properties of crystals as well as inclusion of liquid and impurities in the crystals.