Studies on Diffusion in Alginate Gels. II. Effect of Acid and Subsequent Re-exposure to Calcium on the Diffusion of Caffeine and Theophylline in Alginate Gel Films

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Abstract
The aim of this research was to investigate the effect of acid exposure and calcium re-exposure on the diffusion of caffeine and theophylline through calcium alginate gel films. Diffusion was measured using side-by-side glass cells, before and after the films were exposed to simulated gastric fluid (SGF) USP minus pepsin. The permeability increased by about 15-fold for theophylline and 48-fold for caffeine after 5 min SGF exposure. There was no significant further increase by prolonging the exposure time to 4 hr. The diffusion of both drugs was less than through alginate gel films that were not cross-linked with calcium but were gelled in SGF. Treatment of the calcium alginate gel films with SGF depleted the films of all of their calcium content. Calcium alginate gel films that were exposed to SGF for a constant period of 15 min, were re-exposed to 0.34 M calcium chloride solution for periods up to 24 hr. The calcium content returned to 80% of the level in the original calcium alginate films and diffusion was reduced, but not to the level that was observed in the original calcium alginate films. It was concluded that the effect of SGF on calcium alginate was very rapid and that the increase in drug diffusion observed was probably due to removal of calcium from the gel. It was also concluded that the original diffusion properties and calcium content could only be partially regenerated by re-exposing the acid-exposed films to calcium chloride.
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