Mathematical modelling and experimental studies with physiologically sensitive polymers
Abstract
The transport of physiological solution into cationic polymers and the associated solute transport therefrom were investigated. Cationic polymers of poly(diethyl aminoethyl methacrylate -co- 2-hydroxyethyl methacrylate), poly(diethyl aminoethyl acrylate -co- 2-hydroxyethyl methacrylate) and poly(3-methacryl amidopropyl trimethyl ammonium chloride -co- 2-hydroxyethyl methacrylate) were synthesized using free radical polymerization with a thermal initiator. The ensuing polymers were characterized using differential scanning calorimetry and dynamic mechanical analysis. Gravimetric studies were carried out in citrate-phosphate-borate buffer solution to understand the transport behavior as a function of physiological parameters such as the pH, ionic strength and the nature of ions present in the solution. The glassy-rubbery transition in the polymer was observed experimentally and the glassy-rubbery front velocity was measured as a function of the pH of the physiological solution. Polymer characteristics like the molecular weight between crosslinks were measured and used to calculate the polymer-solution interaction parameter. The mesh size of the polymer networks was calculated as a function of time. Release systems were prepared by loading the polymers with oxprenolol HCl, albumin, insulin and myoglobin. Drug release was monitored with a UV-Vis spectrophotometer. The effect of pH of the release medium on the release kinetics was studied. The effect of concentration of ionizable groups in the polymer on the release was studied and the interaction of ionic drugs with the ionic polymers was investigated. The transport of physiological solution and the subsequent drug release from these polymers were modelled using the generalized Stefan Maxwell equations. A generalized form of the Frisch (1978) equation was used for water transport and a Nernst-Planck type equation was used for ion transport. This model was solved numerically for the case of a thin slab. Structural changes occurring in the polymer network such as the glassy-rubbery transition and swelling were also taken into account. The partition of ions between the polymer and solution was modelled using the concept of Donnan equilibrium. The model was subsequently modified to incorporate an ionic stress generated by the ionization of the pendant groups along with the stress due to the glassy-rubbery transition. A model was also developed to describe the swelling of the polymer in terms of the Hamiltonian of the system. The model parameters were successfully measured using experiments. Solute transport from systems containing ionic drugs which interact with the ionic polymer was also described with these models. The results of these models demonstrated clearly the effect of the pH, ionic strength and the concentration of ionizable groups on the swelling and release behavior.
Degree
Ph.D.
Advisors
Peppas, Purdue University.
Subject Area
Chemical engineering|Polymers|Pharmaceuticals
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