(539d) Continuous Heterogeneous Crystallization and the New Method of Making Tablets

Authors: 
Yazdanpanah, N., Food and Drug Administration
Myerson, A. S., Massachusetts Institute of Technology
Trout, B. L., Massachusetts Institute of Technology
Jensen, K., Massachusetts Institute of Technology
A novel continuous heterogeneous crystallization process was developed, which the active pharmaceutical ingredient is crystallized directly on the surface of an excipient within the crystallizer. The product is then directly formed into tablets without the need for complex downstream processing steps such as milling, sieving, granulation, and blending. The innovative process has no particle processing and handling unit operation. The APIs and excipients systems selected by study of molecular interaction mechanisms, and surface functionality of substrate. The effect of various process parameters on the process stability and drug loading were studied.

Within the range of our analysis, proportional drug loading can be easily tailored for a wide range depending on required drug dosage per tablet. The fully continuous processes, and eliminating the downstream steps result in producing crystalline compounds and final form (tablets) in significantly faster, more efficient, with lower footprint, and more economical. This novel approach eliminates almost all the conventional unit operations in the drug product process, by connecting the API purification and crystallization step directly to the tablet making final stage.

KEYWORDS: Continuous manufacturing, Heterogeneous nucleation, Surface facilitated nucleation, Drug product