The extended release properties of HPMC matrices in the presence of dietary sugars

The mechanisms and structure-activity by which dissolved dietary sugars influence drug release from hydroxypropyl methylcellulose (Methocel® K4M) matrices were investigated. Drug release was retarded at lower sugar concentrations, but above a critical solute concentration (SCRIT), there was marked acceleration of release. Studies of early gel layer formation suggested this resulted from sugar-induced suppression of HPMC particle swelling and coalescence, leading to gel structures with poorer diffusion-barrier properties and reduced resistance to physical erosion. Sucrose, lactose, D-glucose, D-galactose and D-fructose all exhibited this pattern but SCRIT values varied widely between sugars (0.5 M lactose, 1.15 M D-fructose). A polynomial relationship (r2 = 0.994) existed between SCRIT and the ability of the sugar to depress the polymer sol–gel transition temperature (ΔCPT). Structure activity relationships across a wide range of sugars suggested ΔCPT was related to molar hydroxyl number, the orientation of the C4 hydroxyl and the β 1→4 linkage, all factors which influence sugar compatibility with water structure. The study demonstrates how sugars in high concentration can directly influence the performance of the gel diffusion barrier and matrix drug release characteristics. There is therefore potential for influencing drug release kinetics when high concentrations of sugars are co-administered in the fed state or when they are present in HPMC ER formulations.

Retarded particle coalescence during gel-layer formation on the surface of a HPMC matrix tablet hydrating in 0.7 M sucrose.Figure optionsDownload as PowerPoint slide