Acrylic microspheres for oral controlled release of the biguanide buformin.

ABSTRACT

Spherical microparticles based on methacrylic acid-methyl methacrylate copolymer have been developed. The method chosen for the preparation of such microparticles was suspension radical copolymerization of acrylic comonomers in the presence of the ethyleneglycol dimethacrylate as crosslinking agent. The microparticles obtained were characterised by inverse size exclusion chromatography, scanning electron microscopy, swelling degree and exchange capacity. The porous volume of the microspheres ranged from 0.086 ml/g for the microparticles produced by a methacrylic acid/methyl methacrylate ratio of 1/3 and a 10% degree of crosslinking, to 8.57 ml/g for the microparticles produced by a methacrylic acid/methyl methacrylate ratio of 3/1 and 2% degree of crosslinking (in 0.1 N NaCl in phosphate buffer pH 7.4). Also the pore diameter of the swollen microparticles ranged from a few to 120 A. Buformin tosylate - a classical hypoglycaemic drug - was included in the polymer network of the microparticles during the polymerization process. Due to the water solubility of the drug and its low solubility in the organic phase, the entrapment yield did not exceed 15%. However the amount of encapsulated drug as well as the drug released from the microparticles, was dependent on the methacrylic acid/methyl methacrylate ratio, the degree of crosslinking and solvent/comonomers ratio.