Polymorph Control of Micro/Nano-Sized Mefenamic Acid Crystals on Patterned Self-Assembled Monolayer Islands

The nucleation of organic molecular compounds is a stochastic process and is difficult to control. The problem becomes even more complex when the compound has two or more polymorphic forms that can concomitantly nucleate. In this work, patterned self assembled monolayers (SAMs) are employed, on which a large number of identical experiments can be conducted. SAMs can be an effective way to induce heterogeneous nucleation and were used in this work to generate the desired polymorphic form based on the chemical interactions. Seven different self assembled monolayers were employed to study the nucleation behavior of the nonsteroidal anti-inflammatory drug mefenamic acid [MA, N-(2,3-xylyl)anthranilic acid]. The results show that SAMs forming a strong interaction with the -COOH group of MA molecules preferably produced form II. The effects of temperature, solvent, droplet size, and concentration on the nucleation kinetics of MA were also explored The ability to prepare crystalline MA as small as similar to 300 nm while controlling the polymorphic form was demonstrated