The influence of substituted phenols on the sol:gel transition of hydroxypropyl methylcellulose (HPMC) aqueous solutions

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 pKa, Log P and other molecular descriptors) and ΔCPT 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 physicochemical 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.