Selective crystallization of D-Mannitol polymorphs using surfactant self-assembly

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Abstract

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 δforms of d-mannitol, 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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Penha, F. M., Gopalan, A., Meijlink, J. C., Ibis, F., & Eral, H. B. (2021). Selective crystallization of D-Mannitol polymorphs using surfactant self-assembly. Crystal Growth and Design, 21(7), 3928–3935. https://doi.org/10.1021/acs.cgd.1c00243

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