(451a) Engineering Co-Crystals: Solving a Three Dimensional Problem | AIChE

(451a) Engineering Co-Crystals: Solving a Three Dimensional Problem


Chadwick, K. - Presenter, Massachusetts Institute of Technology
Ling, J., Purdue University

Enhancing the bioavailability of poorly water soluble drugs represents an outstanding challenge in pharmaceutical manufacturing. Engineering a crystal form of the Active Pharmaceutical Ingredient (API) that enhances dissolution and/or solubility is often a necessity for optimizing bioavailability. API co-crystals have the ability to greatly enhance the solubility and dissolution rate of the drug without altering its biological function. Current strategies for engineering co-crystals are limited to the design of desired intermolecular interactions between API and co-former. However, this approach is often unsuccessful as no consideration is given to whether the molecules can pack efficiently into a 3D structure. To our knowledge, the effect of the size and shape of the API and potential co-formers on co-crystal formation has never been studied.

In this presentation we shall describe the utilization of the Cambridge Structural Database to study how variation in the molecular weight and volume of the co-crystal components affects the probability of successfully obtaining a co-crystal. The effect of optimal co-former size on co-crystal packing density is discussed. Finally, an engineering strategy incorporating both intermolecular interactions and 3D packing affects has been devised. The success of which has been measured by successfully screening for co-crystals with APIs that have not previously been tested.