Release kinetics of procaine hydrochloride (PrHy) from pH-responsive nanogels: theory and experiments

pH-responsive nanogels consisting of methacrylic acid-ethyl acrylate (MAA-EA) cross-linked with di-allyl phthalate (DAP) were synthesized via emulsion polymerization. Drug release studies were conducted under different pHs, drug loading and concentration gradient difference. The drug loading capacity depended on the cross-link density and MAA-EA molar content, where a lower cross-link density and higher MAA-EA molar content resulted in higher loading capacity. A drug selective electrode was used to directly measure the concentration of procaine hydrochloride (PrHy) released from MAA-EA nanogels. More than 50 data points were acquired, where the mathematical fitting to the Berens and Hopfenberg model allowed the parameters describing the contributions of chain relaxation and diffusion process to be determined. The release rate increased with pH and concentration gradient difference due to a reduction in diffusion barrier and higher concentration gradient driving force, respectively, but it decreased with drug loading as the nanogel could not relax from the compact structure as evident from the contribution of Fickian diffusion, phi(F), and chain relaxation, phi(R). A balance between chain relaxation and Fickian diffusion process controlled the release of drugs from these pH-responsive nanogels. Exponential relationships could be established between diffusion coefficient, characteristic relaxation time and various physical parameters, where the drug release kinetics could be predicted in a quantitative manner.