Constant-Rate Drug Release from Novel Anionic Gel Beads with Transient Composite Structure

Abstract

A new anionic composite bead system with a transient membrane–matrix structure, capable of prolonged constant-rate drug release, has been developed from suspension-polymerized poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA). These composite beads have a thin PMMA/MAA surface layer and a core consisting of the sodium salt form of the polymer (PMMA/MANa). The high loading (>20%) of a model drug (oxprenolol HCl) that is achievable in this system from a loading solution concentration as low as 0.5% suggests the formation of a drug–polymer complex in the form of an ionic salt in the core. The release of oxprenolol from such composite beads shows an initial burst effect followed by an extended constant-rate region before leveling off. Apparently, the surface PMMA/MAA layer functions as a transient rate-controlling membrane before it is completely ionized. Because the ionization process is slow, the rate-controlling characteristics of the surface layer and the resulting constant rate of drug release are both sustained for an extended period. The unique feature of the present system is not only its high drug loading capability, but also the transient nature of the rate-controlling surface layer, which is completely ionized towards the latter part of the drug release, thus avoiding prolonged tailing of drug release that is normally associated with permanent membrane–matrix systems.