Thermoreversible gelation of hydroxypropylmethylcellulose in simulated body fluids

The thermoreversible gelation of hydroxypropylmethylcellulose (HPMC) in simulated intestinal/gastric fluids (SIF/SGF) was monitored by microcalorimetry (micro-DSC), turbidity and rheometry. Both SGF and SIF facilitated sol–gel transition in HPMC without changing the patterns of gelation behavior. The sol–gel transition was found to be an entropy driven and temperature dependent process. Solution isotopic effects using Deuteraed water (D2O) yielded a linear decrease in the temperature of endothermic maximum (Tmax) with the increase in the molar ratio of D2O, indicating that polymer–polymer direct hydrogen bonding (interchain hydrogen bonding) was involved in the gelation process in addition to hydrophobic association. It was found that the Tmax shifted roughly linear to lower temperature with the increase of SGF/SIF content. This effect can be interpreted by the salting-out effect. Three distinct regions of the enthalpy and entropy changes (ΔH and ΔS) depending on buffer content were observed. However, ΔH and ΔS were linear with HPMC weight concentration. The aqueous solutions of HPMC showed a low critical solution temperature (LCST) and form an elastic gel with increasing temperature. Rheological measurements indicated that the sol–gel transition proceeded in two stages. The gel elasticity was affected by the polymer concentration and buffer content. The results obtained from different techniques are consistent and show similar trends.