The effect of salts and pH buffered solutions on the phase transition temperature and swelling of thermoresponsive pseudogels based on N-isopropylacrylamide

Abstract

The temperature sensitive nature of poly(N-isopropylacrylamide) makes it an attractive candidate for controlled drug delivery devices. A series of temperature responsive poly (N-isopropylacrylamide)-polyvinyl pyrrolidinone random copolymers were produced by free radical polymerisation using 1-hydroxycyclohexylphenyketone as a UV-light sensitive initiator. The chemical structure of the xerogels was characterised by means of Fourier transform infrared spectroscopy (FTIR). The copolymers possess a lower critical solution temperature (LCST) in pure water, but the transition temperature may be affected by the addition of various cosolutes. The LCST of the pseudogels (physically crosslinked gels) was investigated in distilled water and a variety of salt and pH buffer solutions, using modulated differential scanning calorimetry (MDSC) and rheological analysis. The pH buffer solutions prepared mimic the variety of conditions encountered by drug delivery systems administered orally. The pH effects on the LCSTs of the temperature sensitive gels appear not obvious; while the salts used to prepare the pH buffer solutions have a more notable effect (‘salting out effect’) on the phase transition temperature. All swelling studies were carried out on the hydrogels at 37°C in distilled water, pH buffer 1.2 and pH buffer 6.8. The swelling/dissociation behaviour of the gels is found to be highly dependent on the pH buffer solution used, as the salts incorporated in preparing the pH buffer solutions lowers the phase transition of the copolymers to below the test temperature of 37°C, thus making them less soluble.