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.

Date of Award	1986
Original language	English