Water-Soluble Polyanions as Oral Drug Carriers: Poly(sulfopropyl methacrylate potassium-co-alkyl methacrylate)

New synthetic polymeric materials have been investigated as oral controlled release systems based on the theory of ion exchange. The polymeric carriers are water-soluble copolymers consisting of an ionic monomer, sulfopropyl methacrylate potassium salt (SPMK), and hydrophobic monomers of alkyl methacrylate (AMA), methyl methacrylate (MMA) and ethyl methacrylate (EMA). Drug-copolymer complexes were obtained by adding aqueous solutions of model drugs, propranolol HCl, verapamil HCl, diltiazem HCl, and labetalol HCl to aqueous solutions of the copolymers enabling the basic amine drugs to complex to the sulfonate groups of the copolymers. Compact tablets were fabricated from the resultant drug-copolymer complexes and dextrose USP. The drug-copolymer complexes are characterized by differential scanning calorimetry and UV spectroscopic methods. The release kinetics from the drug-copolymer tablets are zero-order and are well described by a mathematical model which is based on a heterogeneous dissociation/erosion controlled mechanism. Varying the copolymer composition by increasing the alkyl side chain length of the AMA comonomer or decreasing the ratio of SPMK to AMA prolong the release kinetics. Other aspects such as the type and solubility of the drug complexed with the copolymers and the ionic strength and pH of the artificial gastric/intestinal fluid buffers were also investigated.