The effect of the aqueous solubility of xanthine derivatives on the release mechanism from ethylcellulose matrix tablets

Release data from ethylcellulose (EC) matrix tablets was analyzed to determ ine which release equation provides the best fit to the data and to observe the effect of drug solubility on the release mechanism(s). Tablets were pr epared by direct compression of drug, EC, and lubricant in an appropriate m ass ratio to achieve a high and a low drug loading. Theophylline, caffeine, and dyphylline were selected as non-electrolyte xanthine derivatives with solubilities from 8.3 to 330 mg/ml at 25 degrees C. Drug release studies we re conducted in 37 degrees C water with UV detection at 272 MI. Several equ ations to characterize release mechanisms were tested with respect to the r elease data. Drug diffusion, polymer relaxation, and tablet erosion were th e mechanisms considered. Parameters were generated and ANOVA data presented by WinNonlin Pro(R) software. The Akaike Information Criterion was also co nsidered to ascertain the best fit equation. At high drug loading, drug was released by a diffusion mechanism with a rate constant that increased with an increase in aqueous solubility. At low drug loading, polymer relaxation also became a component of the release mechanism. However, its contributio n to drug release was less pronounced as solubility decreases, becoming neg ligible in the case of theophylline. (C) 1999 Elsevier Science B.V. All rig hts reserved.