The objective of this program is to build a platform technology based on developing membrane-crystallization technology to produce crystals of active pharmaceutical ingredients in which the crystal size and crystal form polymorph or pseudo-polymorph are controlled. Control of crystal size within a narrow range is an important part of pharmaceutical crystallization, as is the ability to ensure that the desired crystal form (polymorph) is produced at all times. This proposal addresses this general manufacturing need for control of crystal size and crystal size distribution, employing crystallization of model solids by solvent removal in a membrane permeator. Compact Membrane Systems has a number of projects and established products in removing small molecules from liquids and gases through these membranes. The unique principle of solvent removal proposed herein will lead to the development of a new platform for CMS membrane capabilities. Such a platform would help to advance the technology for the reliable and reproducible production of pharmaceutical crystalline ingredients and, thereby, assist in the overall effort to improve the process analytical technology sought by the Food and Drug Administration. The advanced level of control offered by our membrane technique, coupled with a tailored, narrow crystal size distribution, has the potential to impact the pharmaceutical industry greatly where broad size distributions lead to the need for excessive post-precipitation processing, such as milling and sieving to reject over- and under-sized crystals. The purpose of this SBIR Phase I project is the demonstration of this technology that can be applied successfully to a large number of processes and products that involve crystalline solids. In pharmaceutical manufacturing, control of particle size and size distribution is paramount for uniform drug delivery and assimilation (""""""""bioequivalency"""""""") within the human body.
Project Narrative A pharmaceutical product with more consistent drug delivery and with better bio-equivalency will result from the development of the membrane reactor. The drug manufacturing process will also be simplified by eliminating unnecessary process steps related to particle size qualification.