Continuous Plug Flow Crystallization of Pharmaceutical Compounds
Alejandro J. Alvarez and Allan S. Myerson. Department of Chemical and Biological Engineering, Illinois Institute of Technology, Perlstein Hall, Suite 127, 10 W. 33rd Street, Chicago, IL 60616
The present study introduces the application of continuous crystallization to control the critical properties of a pharmaceutical product. Most of the active pharmaceutical ingredients (API) of the pharmaceutical products are crystals of small organic molecules. The effectiveness of the API depends on key characteristics of the crystals. One of the relevant characteristics is the Particle Size Distribution, which affect the transport of the API through the circulatory system to the target organs. Particles with small size and narrow size distribution are required for efficient drug delivery. In order to obtain small crystals with narrow Particle Size Distribution, this research work follows an approach based on antisolvent crystallization with high supersaturation levels in a continuous crystallizer operating at plug flow conditions. The process is mathematically modeled using the Population Balance Equations. An optimization problem is solved to estimate the model parameter s. Particle Size Distribution was measured with Laser Diffraction methods, and the crystallization process was monitored measuring concentration of the solute in the liquid phase with Ultraviolet Spectroscopy (UV). As a result of the study, a process configuration is proposed, which is able to produce API crystals with controlled size and narrow size distribution.