Hydroxypropyl methylcellulose (HPMC) is frequently used as a rate control polymer in sustained release hydrophilic matrices. Certain salts and commercial drugs can alter the physiochemical properties ofHPMC and the performance of sustained release matrices. To aid formulation development an understanding of the interaction between the polymer and additives is crucial. (, Near-infrared spectroscopy was used to examine the effect of salts on the structure of water. Salts can alter the structure of water in a manner analogous to temperature. The influence of anions on the solubility ofHPMC appears to result from their ability to restructure water. ATR-FTIR spectroscopy and oscillatory rheology were used to examine the sol:gel transition of HPMC solutions at elevated temperatures. The spectroscopy study revealed evidence of increased hydrophobic methyl interactions during the phase transition. Pre-gelation changes in the elastic properties of the polymer solution were detected in the rheological study, these were ascribed to the progressive ' disruption of native cellulosic 'bundles'. The model NSAIDs studied (mefenamic acid, meclofenamate sodium, and flufenamic acid), increased the aqueous solubility of HPMC, probably by forming micelles at elevated concentrations, into which hydrophobic regions of the polymer solubilise. An interaction between HPMC and the carboxylate ion of the NSAIDs was detected in the ATR-FTIR study, this may account for the changes observed in the physiochemical properties ofthe polymer. A confocal scanning laser microscopy method was developed, utilising the fluorophore Congo Red, to monitor the critical early stages of gel layer formation around hydrating HPMC matrices. In the presence of 0.75 M sodium chloride the polymer particles clearly failed to form a coherent gel layer, and so accelerating the disintegration of the formulation.