Noncross-linked copolymers of dimethylaminoethyl methacrylate and methacrylic acid as oral drug carriers

The purpose of this study was to synthesize new water-soluble ampholytic copolymers consisting of tertiary amine and carboxylic acid pendent groups for oral drug carriers. The polymers were prepared with a 1:1 molar ratio of dimethylaminoethyl methacrylate and methacrylic acid by free radical polymerization. After polymerization, polymer rods were recovered, dissolved (or swollen) in de-ionized water, and freeze-dried before obtaining fine powders. Drug release experiments with various drugs, representing a variety of drug solubility and types of amine, were carried out with compressed tablets (total weight of 600 mg) containing a variety of basic drugs in pH's of 1.5 and 7. Surprisingly, zero-order release kinetics even from a tablet geometry has been obtained with drug loading ranging from 20-50%. Drug release in pH 7 maintains a zero-order rate up to 80-85% release after a slight initial burst, whereas in pH 1.5 one may not find the initial burst and zero-order kinetics is extended up to 90-95% release. Drug release becomes faster in pH 1.5 than pH 7 due to the faster rate of protonation of the tertiary amine in acidic conditions. The release of basic drugs in pH 1.5 is not significantly different even with varying solubility and types of amine (primary, secondary, and tertiary). However, different drug release profiles in pH 7 are observed with different types of amine and solubility.