Linearization of drug delivery from sustained-release dosage forms, synthetic gel systems

A linear, apparent zero-order, in vitro release profile may be approximated from triple-pressed tablets using synthetic gum systems in the first and second press coats. This is coupled with varying concentrations of the actives (Melperone HCl, Diethylpropion HCl, and Dyphylline) in the core and press coats. The approximately linear release function obtained from these tablet systems is in stark contrast to a supposedly prolonged release tablet (comparative formulation) from the literature, which actually releases by the square root of time function characteristic of diffusion control. Addition of a placebo press coat to the outside of the synthetic gum systems simply increases the lag times for release (while the placebo coat is undergoing hydration, etc.). The linearity following the lag is reminiscent of saturation kinetics. Results suggest that the almost linear release profile is a function of the concentration of the various layers (core first and second press coats) coupled with the gelation characteristics of the synthetic gums. This zero-order release does not hold for the systems of the comparative formulation taken from the patent literature.