Influence of drug solubility on the release from hydrophilic matrix systems with a non-uniform distribution of the components

Hydrophilic matrices are the most widely used dosage forms for the preparation of prolonged release systems because of simple and economic manufacturing and of flexibility in modulating the drug release rate. However, they generally do not allow to obtain zero-order release kinetics due to the fact that i) the drug particles present on the surface tend to dissolve readily, giving rise to the so-called "burst effect", ii) the diffusion path that the drug molecules must cross (thickness of the swollen polymer layer) progressively increases and iii) the interface between the glassy and rubbery portions of the matrix progressively decreases. Regarding drug delivery systems aimed at attaining zero-order release, improvements have been achieved either through geometry changes or by preparing matrix units characterized by a non-uniform distribution of the various components, in particular the active ingredient. The system NUDMAT (Non-Uniform Distribution Matrix) consists of a hydrophilic matrix prepared applying successive layers of formulations at different concentrations of drug onto inert cores by means of powder layering technique. Methocel® K15M, a high-viscosity HPMC (hydroxypropyl methylcellulose) grade, was used as the matrix-forming agent. Systems containing drugs with different solubility (acetaminophen, lansoprazole and potassium salt of losartan) were prepared and evaluated for in vitro performance. Zero-order release was obtained with all the model drugs selected, as assessed through statistical analysis of data by the Durbin-Watson equation. The overall results pointed out the versatility and robustness of the NUDMAT delivery platform irrespective of the solubility characteristics of the active ingredient incorporated.