Structure and physical behavior of pH-sensitive anionic copolymeric networks
Abstract
pH-Sensitive polymer networks are crosslinked polymer electrolytes containing pendant ionizable groups. Due to the presence of ionizable fixed charges these polyelectrolytes show pH-dependent dynamic as well as equilibrium swelling behavior. Loosely crosslinked polyelectrolytes containing weakly ionizable fixed charges such as -COOH or -NH$\sb2$ groups show a drastic change in their equilibrium as well as dynamic swelling ratios. This property can be used in the design of stimuli-responsive drug delivery systems. The change in the pH would act as an input and the solute which is incorporated into this polymer network would be released. Loosely crosslinked copolymers of 2-hydroxyethyl methacrylate with either methacrylic acid or acrylic acid were synthesized using solution polymerization. Their dynamic and equilibrium swelling characteristic were dependent upon pH, ionic strength, buffer composition and the nature of counterion. The mechanism of water diffusion was non-Fickian in all the buffered swelling media. However, the diffusion mechanism remained Fickian in all the unbuffered systems studied and at pH lower than the pK$\sb{\rm a}$ of gels. The pK$\sb{\rm a}$ of these gels was in the range of 5.5 to 6.5. The swelling mechanisms were explained using Donnan equilibrium and rate of ion exchange. The T$\sb{\rm g}$ of these copolymers were in the range of 100$\sp\circ$ to 130$\sp\circ$C. These copolymers were thermally stable up to 200$\sp\circ$C as observed by thermogravimetry and differential scanning calorimetry. Absorption of water by a glassy polymer leads to a formation of glassy-rubbery interface due to plasticization of the polymer. An experimental technique was used to quantify the interfacial stresses developed during the glassy-rubbery transition, by measurement of the swelling force. The dynamic as well as the maximum swelling forces were found to be functions of the ionic content and the pH of the external swelling medium. The diffusional-relaxational coupled mechanism was important in the development of the dynamic swelling force. The solute release behavior of low molecular weight drugs from these glassy polymer networks was studied and it was found to be a function of pH, ionic strength, free water content, and the nature of dissolution medium. The initial rate of drug release was found to be higher in buffered dissolution medium as compared to water and with an increase in drug loading in the polymer. The drug release mechanism was found to be non-Fickian in all the release studies. The drug diffusion coefficients were found be of the order of 10$\sp{-7}$ cm$\sp2$/s. Drug-polymer compatibility studies showed that the drug was uniformly distributed in the polymer matrix and it was present in the form of solid solution or was molecularly dispersed.
Degree
Ph.D.
Advisors
Peppas, Purdue University.
Subject Area
Chemical engineering|Polymers|Pharmacology
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