Measurement of Diffusion Coefficients of Theophylline and Aminophylline in Carrageenan Gel

Abstract

Diffusion coefficients of theophylline and aminophylline in carrageenan gels of various concentrations at 37°C were measured by means of drug sorption and permeation tests using a diffusion cell. The permeation data were analyzed by Rogers' method and a lag time method. The diffusion coefficients determined by Rogers' method coincided reasonably well with those determined by means of the drug sorption test. They were 0.54 to 0.81×10^-5 cm²/s and 0.43 to 0.86×10^-5 cm²/s for theophylline and aminophylline, respectively. The diffusion coefficients determined by the lag time method were larger than those determined by the other methods. The diffusion coefficient of aminophylline was slightly larger than that of theophylline at the same initial concentration, e. g. 5.0×10^-3 (g/ml). Ethylenediamine might loosen the carrageenan network, thus enhancing the diffusion of the drug. The diffusion coefficient was dependent upon the carrageenan concentration in the gel. The gel thickness bad a less important effect on the diffusion coefficient, although the lag time greatly depended on it. The diffusion coefficients were also determined by means of drug release tests using the same diffusion cell. When the drug was dispersed in the gel as a solution, the diffusion coefficient agreed fairly well with that determined in the sorption test. In carrageenan with dispersed solid particles, the drug transfer rate was enhanced by hydrodynamic flow from the voids left after dissolution of the particles in the gel.