Interfacial Engineering of Tolbutamide Polymorphs Using Tunable Self-Assembled Monolayers.

Drug polymorphism affects crystallization behavior and material properties. Prior research has shown that functional surfaces can influence nucleation. However, no prior work had resolved how SAMs might selectively promote specific polymorphs. This gap motivated the use of thiol-based SAMs to control nucleation. The study aimed to determine if SAMs could guide TB crystallization. The field lacked a clear link between SAM functional groups and polymorph outcomes. This paper investigates that link. The work builds on existing knowledge of TB's polymorphic behavior. It introduces a novel approach using SAMs to direct nucleation.

The study aimed to explore how SAMs could influence TB polymorph formation. TB is known to crystallize into multiple forms. The specific problem was understanding how SAM surface chemistry affects nucleation. The motivation came from the need to control drug crystallization. The goal was to achieve selective polymorph nucleation. The approach focused on SAM functional groups. The study sought to identify which groups promote specific polymorphs. It aimed to provide a framework for designing functional surfaces.

The researchers used ten thiol-based SAMs with varied functional groups. These SAMs were designed to interact with TB during crystallization. The surfaces included -COOH, -OH, pyridine, and others. TB crystallization was observed on these SAMs. X-ray diffraction confirmed the polymorphs formed. Thermal analysis and Raman spectroscopy were used for characterization. Microscopic imaging tracked crystal growth. DFT analysis modeled conformational barriers between polymorphs. BFDH and Hirshfeld surface analysis predicted interactions.

Controlled nucleation of polymorph II was achieved on certain SAMs. Metastable polymorphs IV and V were also selectively formed. Functional groups like -COOH promoted polymorph II. Pyridine and benzimidazole surfaces favored polymorph IV. Fluorine-containing SAMs induced polymorph V. The SAMs altered TB's nucleation kinetics. X-ray and Raman confirmed the polymorph identities. DFT analysis revealed energy barriers between polymorphs. BFDH and Hirshfeld surface analysis explained the interactions.

The study suggests that SAMs can guide TB polymorph nucleation. The functional groups on SAMs influence which polymorph forms. The results align with the authors' claim that surface chemistry controls crystallization. The findings support the idea that SAM design affects nucleation outcomes. The authors propose that SAMs offer a tunable platform for drug crystallization. The study confirms that TB's polymorphs can be selectively induced. The authors suggest that this approach could be extended to other drugs. The conclusions reflect the abstract's claims without generalization.