PREPARATION OF BIODEGRADABLE POLY(LACTIC-CO-GLYCOLIC) ACID MICROSPHERES AND THEIR INVITRO RELEASE OF TIMOLOL MALEATE

Poly(lactic-co-glycolic) acid, PLG, 50:50 microspheres containing homogeneously dispersed timolol maleate were prepared in an oil-in-oil solvent evaporation method. By varying the PLG concentration in the microsphere preparation, different particle sizes were obtained. A constant drug loading of about 2% (w/w) independently of PLG and timolol maleate concentration was obtained. As the drug loading was low and the particles exhibited a slow release of drug, it is suggested that the release of drug was due to polymer degradation rather than to pore diffusion. Timolol release was initiated with a small burst. After a lag time, a second period of extensive and rapid release of drug was observed, This secondary burst was accompanied by the collapse of the polymer matrix. The release from microspheres with polyethylene glycol (PEG) incorporated showed no secondary burst. After the secondary burst there was very little, if any, further release of drug. The presence of detergent in the release medium resulted in a smooth and relatively fast release rate from the particles. In this case no secondary burst was detected.