Analysis of drug distribution in hydrogels using Fourier transform infrared microscopy

Purpose. The purpose of this work was to study solute (drug and protein)/polymer interactions that affect solute diffusion in and subsequent release from swellable dosage forms based on environmentally responsive, pH-sensitive polymer networks. Methods. Ionizable pH-sensitive hydrogels were synthesized by free-radical polymerization of acrylic acid (AA) and 2-hydroxyethyl methacrylate (HEMA) with ethylene glycol dimethacrylate as crosslinking agent. The degree of crosslinking and degree of hydrophilicity were controlled by varying the relative concentration of crosslinking agent and comonomer, respectively. The role of solute distribution within the hydrogels as related to the transport behavior was investigated by Fourier transform infrared (FTIR) microscopy. Results. The solute-loaded hydrogels were cryotomed into 4 pm thin sections. The concentration profile of the solute was constructed from the two dimensional intensities measured by monitoring the infrared vibrational band indicative of that compound in the x and y direction. These studies indicated that the model solute, oxprenolol HCl, was evenly distributed throughout the bulk and surface of the hydrogel samples. Solute/polymer interactions were investigated as a function of the polymer composition and swelling media pH. The concentration profiles of oxprenolol HCl solution loaded into PAA and P(AA-co-HEMA) hydrogels were analyzed by scanning electron microscopy by FTIR microscopy. For hydrophilic polymers (hydrogels) containing ionizable pendant groups, the molecular weight between crosslinks, the degree of swelling, and the degree of ionization were altered by local changes in pH and ionic strength. Conclusions. The data demonstrated that it is possible to evaluate the polymer/solute interactions by using FTIR microscopy.