Novel Polymeric Controlled Release Systems

Abstract

The primary object of this research has been to evaluate the potential of biodegradable polymers as matrices for macramolecular controlled drug release systems. Initial work was carried out on the in vitro breakdown of members of a novel poly ester copolymer series - polyhydroxybutyrate-co-hydroxyvalerate, in various aqueous buffers by bulk and surface measurements of the varying physical forms of the copolymer matrices. In line with the reported hydrolytic degradation of other polyesters the degradation was found to be by a predominantly homogeneous (bulk) mechanism. The initial molecular weight, copolymer composition and physical form of the polymer matrix determining the rate of hydrolysis. Comparison with established biodegradable suture materials showed a relatively slow rate of hydrolysis for the butyrate / valerate copolymers. However, differences in matrix molecular weights and crystallinities did make equivalent comparisons difficult. A link between matrix surface physical properties and the extent of bulk degradation was found, with the surface techniques providing a more detailed reflection of the extent of bulk matrix hydrolysis than weight loss measurements during the initial degradation stages. Drug release in the form of a series of macromolecular FITC dextran dyes was followed from two types of polyhydroxybutyrateco- hydroxyvalerate matrices (i.e. solvent cast films and cold compressed tablets). Release was found to occur predominantly by diffusion with matrix degradation playing an insignificant part in dye dissolution. Contrary to expectation, the rate of dye release increased with increasing dye molecular weight. This was due to changes in matrix porosity rather than dye diffusivity. Tablet dye release was found to be effected by the addition of various excipients, with matrix porosity governing the overall! release rate. It is suggested that the tabletted form could be used as sustained release non-disintegrating oral dosage forms.