Dataset Information

Designer Gelators for the Crystallization of a Salt Active Pharmaceutical Ingredient-Mexiletine Hydrochloride.

ABSTRACT: We report an approach to obtain drug-mimetic supramolecular gelators, which are capable of stabilizing metastable polymorphs of the pharmaceutical salt mexiletine hydrochloride, a highly polymorphic antiarrhythmic drug. Solution-phase screening led to the discovery of two new solvated solid forms of mexiletine, a type C 1,2,4-trichlorobenzene tetarto-solvate and a type D nitrobenzene solvate. Various metastable forms were crystallized within the gels under conditions which would not have been possible in solution. Despite typically crystallizing concomitantly with form 1, a pure sample of form 3 was crystallized within a gel of ethyl methyl ketone. Various type A channel solvates were crystallized from gels of toluene and ethyl acetate, in which the contents of the channels varied from those of solution-phase forms. Most strikingly, the high-temperature-stable form 2 was crystallized from a gel in 1,2-dibromoethane: the only known route to access this form at room temperature. These results exemplify the powerful stabilizing effect of drug-mimetic supramolecular gels, which can be exploited in pharmaceutical polymorph screens to access highly metastable or difficult-to-nucleate solid forms.

SUBMITTER: Andrews JL

PROVIDER: S-EPMC9635620 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Designer Gelators for the Crystallization of a Salt Active Pharmaceutical Ingredient-Mexiletine Hydrochloride.

Andrews Jessica L JL Kennedy Stuart R SR Yufit Dmitry S DS McCabe James F JF Steed Jonathan W JW

Crystal growth & design 20221012 11

We report an approach to obtain drug-mimetic supramolecular gelators, which are capable of stabilizing metastable polymorphs of the pharmaceutical salt mexiletine hydrochloride, a highly polymorphic antiarrhythmic drug. Solution-phase screening led to the discovery of two new solvated solid forms of mexiletine, a type C 1,2,4-trichlorobenzene tetarto-solvate and a type D nitrobenzene solvate. Various metastable forms were crystallized within the gels under conditions which would not have been po ...[more]

PMID: 36345390

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Dataset Information

Designer Gelators for the Crystallization of a Salt Active Pharmaceutical Ingredient-Mexiletine Hydrochloride.

Publications

Designer Gelators for the Crystallization of a Salt Active Pharmaceutical Ingredient-Mexiletine Hydrochloride.

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