Designer Gelators for the Crystallization of a Salt Active Pharmaceutical Ingredient-Mexiletine Hydrochloride.
Cryst Growth Des
; 22(11): 6775-6785, 2022 Nov 02.
Article
em En
| MEDLINE
| ID: mdl-36345390
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cryst Growth Des
Ano de publicação:
2022
Tipo de documento:
Article