Selective Crystallization of d-Mannitol Polymorphs Using Surfactant Self-Assembly

Selective crystallization of polymorphs is highly sought after in industrial practice. Yet, state-of-the-art techniques either use laboriously engineered solid surfaces or strenuously prepared heteronucleants. We propose an approach where surfactants in solution self-assemble effortlessly into mesoscopic structures dictating the polymorphic outcome of the target solute. Sodium dodecyl sulfate (SDS) surfactant is used as a tailored additive to crystallize different polymorphic forms of a model active pharmaceutical ingredient, d-mannitol. Different mesoscopic phases of SDS template particular polymorphs: packed monolayers, micelles, and crystals favored the β, α, and δ forms of dmannitol, respectively. A synergistic effect of topological templating and molecular interactions is proposed as the rationale behind the observed selective crystallization of polymorphs. This crystal engineering technique suggests that surfactant self-assemblies can be used as tailored templates for polymorphic control.

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About this article: Frederico Marques Penha, Ashwin Gopalan, Jochem Christoffel Meijlink, Fatma Ibis, and Huseyin Burak Eral, Crystal Growth & Design 2021 21 (7), 3928-3935 DOI: 10.1021/acs.cgd.1c00243

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