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

F. Marques Penha, A. Gopalan, J.C. Meijlink, F. Ibis, H.B. Eral

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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 δ forms 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.
Original languageEnglish
Pages (from-to)3928-3935
JournalCrystal Growth & Design
Volume21
Issue number7
DOIs
Publication statusPublished - 2021

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