Low-density poly(dl-lactide-co-glycolide) foams for prolonged release of isoniazid

Abstract Incorporation of the antitubercular drug isoniazid, INH, into low density poly( dl -lactide-co-glycolide), PLGA, foams of high interstitial void volume prior to high pressure extrusion is shown to prolong the in vitro release of INH. In vitro studies indicate that the duration of INH release can be significantly increased, the early burst dramatically 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 concentration. The morphology of foams prepared by lyophilization of glacial acetic acid solutions of the polymers produces leaflet or platelet structures. Matrices were prepared by (1) extruding INH impregnated foams previously compacted and ground to 125–180 microns, (2) directly extruding impregnated foams without prior compaction and grinding, and (3) extruding 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) × 10 −4 , 2.1(±0.3) × 10 −4 , and 3.2(± 1.6) × 10 −4 cm 2 /day.