The influence of substituted phenols on the solrgel transition of hydroxypropyl methylcellulose (HPMC) aqueous solutions

摘要

The influence of the physicochemical parameters of substituted aromatic molecules on the phase transition from sol to gel of hydroxypropyl methylcellulose (HPMC) has been investigated using a homologous series of substituted phenols. Using a turbimetric methodology, concentration dependent suppression of phase transition temperature of HPMC was observed for phenol and its derivatives, including methyl-, nitro- and chloro-substituted molecules. Although no strong direct relationship between single molecular physicochemical properties of the phenolic compounds (such as pK_a, Log P and other molecular descriptors) and Δ_(CPT) was found for the compounds tested, a successful prediction of behaviour could be obtained by using a combination of parameters. This suggested that the interaction mechanism between HPMC and the substituted aromatic moiety is a complex summation of the different molecular physico-chemical properties. Identification of these potentially deleterious chemical moieties may be of value in a pharmaceutical context when considering preformulation of drug structures containing them. An incompatibility between drug and polymer may be indicative of deleterious effects resulting from formulation with hydrophilic matrix dosage forms containing cellulose ethers such as HPMC.