Drug polymorphs à la carte: Selective growth of stable and metastable polymorphs

INOR 853

Venkat R. Thalladi, thalladi@wpi.edu, Jason R. Cox, and Marta Dabros, mdabros@wpi.edu. Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609
Polymorphism, the ability of a compound to adopt multiple solid-state arrangements, is critical to pharmaceutical drug development and formulation. Thermodynamics dictates that a given modification be the most stable under a set of conditions; whereas the other polymorphs are metastable under the same conditions. Thermodynamic and metastable forms each exhibit distinct advantages and limitations. For example, stable forms exhibit prolonged phase stability; metastable forms have desirable dissolution properties. Selective growth of both types of polymorphs is therefore essential to the rational design of suitable drug formulation. In this work we describe two techniques currently being developed in our laboratory for such selective growth. These techniques involve the crystallization of drug compounds in the presence of attractive and repulsive surface templates and microwave radiation.