DRUG RELEASE FROM GEL BASES - A CASE FOR ENTHALPY-ENTROPY COMPENSATION

Carbopol-based gels have been prepared containing either 0, 10, 20 or 30% W/V of propylene glycol. The in vitro release of a model drug (chlorhexidine) was investigated at four different temperatures, and apparent diffusion constants were calculated. Thermodynamic functions were calculated from the temperature dependence of the apparent diffusion constants, using a modified Arrhenius approach. From the relationships between the enthalpy and free energy values, which were calculated at the harmonic mean experimental temperature, it was concluded that there was a common mechanism of release from gels which contained propylene glycol (only the rate changed as a function of concentration), but that the drug release mechanism was different from the gel without added glycol. Such compensation analysis seems to be a valuable tool for the analysis of drug release data. Comparisons between data analysis using conventional and modified Arrhenius calculations confirmed the possibility of obtaining false correlations from data derived from the conventional approach. The data were compared to published information concerning the release of model drugs from Pluronic F- 127 gels. and it was concluded that the release mechanism was different for the two gel structures.