IN-VITRO CONTROLLED-RELEASE OF ISONIAZID FROM POLY(LACTIDE-CO-GLYCOLIDE) MATRICES

In vitro release kinetics of isoniazid (INH) from a biodegradable poly meric matrix has been investigated for systems prepared under varying fabrication conditions. Matrices were prepared either by evaporation o f co-solutions followed by extrusion under controlled temperature and pressure, or by dry mixing INH with PLGA which had been pre,ground and sieved to isolate specific particle size ranges prior to extrusion. T he effect on release kinetics of loading, polymer particle size, extru sion pressure, and rod diameter was explored. Fractional release as a function of time is shown to fit the Roseman-Higuchi model in that plo ts of (1 - F)1n(1 - F) + F are linear with time where F is the fractio n of drug released at time t. The effect of varying fabrication parame ter values on the slope (identified as the combined rate constant for drug release, K = 4CD/Aa(0)(2)) is as follows: K increases with decrea sing polymer particle size, lower extrusion pressure, lower loading. T he effect of increasing the rod diameter results in a small increase i n K. Other parameter values being equal, solvent cast systems released more rapidly than those prepared without the use of solvent.