A Supramolecular Gel Control of Pharmaceutical Cry.. (GELCRYS)
A Supramolecular Gel Control of Pharmaceutical Crystal Growth
Date du début: 15 avr. 2013,
Date de fin: 14 avr. 2015
"The solid form of drug substances (active pharmaceutical ingredients, API) is of huge importance to the European pharmaceutical industry and the European economy, which makes tremendous investments on crystal structure calculation and empirical polymorph screening. Different crystal forms (polymorphs, pseudopolymorphs, salts or co-crystals) have different bioavailability and solubility, and the crystal morphology significantly affects processing and tabletting behaviour. Here, we propose to develop a novel method for identifying, isolation and screening, of new drug solid forms, particularly the production of previously unknown polymorphs by use of chemically and physically tunable supramolecular gels. A gel fiber represents on the local scale an ordered and controllable array of chemical functionality suitable to act as a heteronucleating surface and hence influence the structure of a growing crystal nucleus of a drug polymorph. In well designed cases the API will bind to the gel in such a way that the short-range periodicity within a gel fibril can match up with a complementary face of a precritical nucleus of a particular solid form and hence stabilize that nucleus relative to homogeneous nucleation. Such ‘active’ gels are expected to catalyse the formation of otherwise unstable or hard-to-nucleate solid forms. This proposal aims to use low molecular weight gels as a medium for the templated growth of APIs and to take advantage of the supramolecular nature of these gels in order to dissolve them and hence recover the crystals. The principal objectives are three fold:(i) Tailor specific gelators to complement the functional groups of target APIs in order to template the growth of novel solid forms by specific solute-gelator molecular recognition.(ii) Establish reversible gelation condition in order to recover the APIs by dissolving the gels.(iii) Show by means of relevant case studies that tailored gelators allow the discovery of novel drug solid forms."
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