(310a) A Novel Microfluidic Platform for Screening of Pharmaceutical Polymorphs Under Hydrodynamically-Controlled Crystallization Conditions
AIChE Annual Meeting
2017 Annual Meeting
Solid Form Selection: Cocrystals, Salts, Solvates, Polymorphs, and Beyond
Tuesday, October 31, 2017 - 8:05am to 8:25am
The majority of oral drugs are delivered in solid forms such as capsules, tablets, powders or suspensions. The physicochemical properties and quality of such drugs strongly depend on their crystalline structure or polymorph, which is controlled during the crystallization process. Various factors such as solvent, temperature, co-solvent, supersaturation, and additives can affect the formation of polymorph. Screening of polymorphs with respect to these factors can be combinatorially tedious and time-consuming. High-density microtiter plates with as many as 1586 wells are commonly employed to screen ~10,000 factors per day. However, the application of microtiter plates for polymorph screening has some practical limitations as the environmental conditions in stagnant wells of the microtiter plate is much different than those in the batch crystallizers. Alternatively, the microfluidic platforms have been used to screen polymorphs using very small quantities (~100 µg) of the drugs in the early stages of developments. Such microfluidic devices locally produce a mixture of crystalline material which is not suitable for the study of nucleation and growth of polymorphs. Here we propose a novel microfluidic platform which mitigates the issues of the previous designs by facilitating nucleation and growth of single crystals. This microfluidic device can effectively screen the aforementioned factors to generate single crystals of polymorphs at the stagnation point while implementing the hydrodynamic conditions which are not considered in the microtiter plate method. In this work, we have screened polymorphs of Carbamazepine using various mole fractions of chloroform:ethanol mixtures and temperatures in the microfluidic device. Further analysis for the measurement of growth rate and morphology are also discussed. The high throughput screening system is also proposed to evaluate multiple crystallization conditions within one single device.