Effect of the morphology of hydrophilic polymeric matrices on the diffusion and release of water soluble drugs

Abstract

Drug release mechanisms from, and diffusion processes in, hydrophilic crosslinked polymeric systems were investigated in two macromolecular states: in the glassy and rubbery states during the early part of countercurrent water diffusion, and in the rubbery state after thermodynamic equilibrium between the network and the surrounding dissolution medium (water) was attained. Dilute, aqueous poly(vinyl alcohol) (PVA) solutions containing theophylline were crosslinked with glutaraldehyde. The crosslinking ratio, X, varied between 0.01 and 0.20 moles glutaraldehyde per mole of PVA repeating unit. Theophylline release from these rubbery matrices was followed as a function of time. It was determined that, within the range of crosslinking ratios studied, the crosslinked macromolecular structure affected the solute diffusion process. Theophylline release from crosslinked PVA slabs, which were originally dehydrated at 30°C, was also measured. The drug release process was significantly impeded in these systems, especially for samples with crosslinking ratio X ≥ 0.10. This behavior was explained in terms of relaxation of the macromolecular chains and possible existence of ordered chain structures. Glass-to-rubber transitions, a result of the countercurrent diffusion of water into the originally dried (glassy) polymer, shifted the fractional release of theophylline from a f( t 1/2) to a f( t n) time dependence, with n taking values between 0.50 and 0.76. This type of release behavior indicates anomalous diffusion mechanisms. These results may be helpful in the development of swelling controlled drug delivery systems.