LOW-DENSITY POLY(DL-LACTIDE-CO-GLYCOLIDE) FOAMS FOR PROLONGED RELEASEOF ISONIAZID

Incorporation of the antitubercular drug isoniazid, INH, into low dens ity poly(DL-lactide-co-glycolide), PLGA, foams of high interstitial vo id volume prior to high pressure extrusion is shown to prolong the in vitro release of INH. In vitro studies indicate that the duration of I NH release can be significantly increased, the early burst dramaticall y reduced, and variation in replicate samples reduced. Control of the specific gravity and interstitial void volume of the foam is achieved by lyophilization of frozen polymer solutions of specified concentrati on. The morphology of foams prepared by lyophilization of glacial acet ic acid solutions of the polymers produces leaflet or platelet structu res. Matrices were prepared by (1) extruding INH impregnated foams pre viously compacted and ground to 125-180 microns, (2) directly extrudin g impregnated foams without prior compaction and grinding, and (3) ext ruding mechanically mixed micronized INH and ground PLGA which had not been prepared as foam. INH release kinetics, analyzed in terms of the Roseman-Higuchi model, confirms that release is diffusion controlled. Diffusion constants for the three methods are 1.2(+/-0.1) X 10(-4), 2 .1(+/-0.3) X 10(-4), and 3.2(+/-1.6) X 10(-4) cm(2)/day.