Drug diffusion mechanism through pH-sensitive hydrophobic/polyelectrolyte hydrogel membranes.

Methylmethacrylate/dimethylaminoethyl methacrylate cross-linked with divinylbenzene is a pH-sensitive hydrogel. We have studied the diffusion mechanisms of drugs with different water solubilities through this hydrogel. A water-soluble model drug (aminopyrine) was used to study the diffusion coefficient changes in different pHs. The results showed a water-content dependent diffusion for this pH-sensitive polycationic hydrogel. However, decreasing the solubility of the drug and increasing the hydrophobic character of the polymer by changing the pH caused a greater affinity (or partition coefficient) between the hydrogel and the drug. Aminopyrine diffusion was shown to follow the free-volume theory, suggesting the 'pore' type mechanism for water soluble drugs, while the 'partition' or 'solution-diffusion' mechanism better described the slow diffusion of water insoluble solutes through this pH-sensitive hydrogel. Comparing the swelling interface number for aminopyrine release through this pH-sensitive hydrogel showed a non-Fickian mechanism in the hydrated form of the hydrogel (pH 1.2), while Fickian in the dehydrated form (pH 7.4).