Diffusion of drugs in acrylic-type pressure-sensitive adhesive matrix. II. Influence of interaction

Abstract

The release of 16 drugs of different molar volumes and functional groups from acrylic-type pressuresensitive adhesive (PSA) matrices was measured. 2-Ethylhexylacrylate (2-EHA) and acrylic acid (AA) copolymer were used to make the PSA matrix. The diffusion coefficient of drugs in the PSA matrix was calculated from the release data using a nonlinear regression analysis. The relationship between the diffusion coefficient of drugs in the PSA matrix and their physicochemical properties such as molar volume and chemical structure was examined. The diffusion coefficient of drugs in the PSA matrix was affected by their molar volume and by the type of functional group present. The observed diffusion behavior was interpreted by the free-volume theory, following classification by functional group and the interaction evaluated between the drug and PSA carboxyl group. The rank order confirmed from the logarithm of diffusion coefficient vs the drug's molar volume profiles (LogD- Mv profile) could not, however, be sufficiently explained by the electrostatic interaction between the PSA component (carboxyl group ) and the drug with various degrees of dipole moment values. Influence of a drug on the polymer-polymer interaction can be estimated by measuring the effect of the drug's loading on its diffusivity in the PSA matrix. A modified WLF equation was used to obtain the interaction parameter, β. The rank order of intensity of the interaction by the model drugs lidocaine, ketoprofen, aminopyrine and dipropylphthalate was evaluated by measuring the β value, and was consistent with that obtained from the LogD- Mv profiles. The absorbance of OH stretching arising from the carboxyl group at 4000 to 2000 cm −1 of the PSA without drugs on Fourier transform infrared spectroscopy ( FT-IR ) was increased with an increase in the acrylic acid content in the PSA, while the absorbance was decreased by the addition of dipropylphthalate, ketoprofen and lidocaine. The extent of the decrease was dependent on the drugs. The results obtained from FT-IR measurement also supported the rank order observed in the diffusion study. A series of these results appeared to indicate that detailed evaluation of interactions such as polymerpolymer, polymer-drug and drug-drug were required for the exact analysis of a drug's diffusion behavior through the polymer matrix (PSA).