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

• Published in: Crystal growth & design 2012-11, Vol.12 (11), p.5521-5528
• Main Authors: Yang, Xiaochuan, Sarma, Bipul, Myerson, Allan S
• Format: Article
• Language: English
• Subjects: Condensed matter: structure, mechanical and thermal properties; Crystalline state (including molecular motions in solids); Crystallographic aspects of phase transformations; pressure effects; Equations of state, phase equilibria, and phase transitions; Exact sciences and technology; General studies of phase transitions; Nucleation; Physics; Structure of solids and liquids; crystallography; Structure of specific crystalline solids
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/cg301092b

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 ∼300 nm while controlling the polymorphic form was demonstrated.