Pulsatile drug release from poly (lactide-co-glycolide) microspheres:: how does the composition of the polymer matrices affect the time interval between the initial burst and the pulsatile release of drugs?

Pulsatile release of estradiol was observed from poly (lactide-co-glycolide) microspheres, of which the monomer composition was 75% lactide and 25% glycolide. Estradiol was monolithically dissolved in the polymer matrices. The microspheres were immersed in a pH 7.4 phosphate buffer saline at 37 degrees C. When estradiol was loaded in microspheres consisting of poly (lactide-co-glycolide) of average molecular weight ((M) over bar w) of 74 000 before degradation, the pulse of estradiol release was observed almost 50 days after the initial burst. On the other hand, if poly (lactide-co-glycolide) of (M) over bar w 44 000 before degradation was used as a material to prepare the microspheres, then estradiol was released in a pulsatile manner almost 20 days after the initial burst effect. It was found that the time interval between the initial burst and the pulsatile release can be regulated by mixing the above two types of poly (lactide-co-glycolide) with different (M) over bar w to prepare microspheres. For example, the pulsatile release of estradiol was observed 30 days after the degradation starts when the microspheres were composed of 50% poly (lactide-co-glycolide) of (M) over bar w 74 000 and 50% poly (lactide-co-glycolide) of (M) over bar w 44 000. In another case where the microspheres were composed of 75% poly (lactide-co-glycolide) of (M) over bar w 74 000 and 25% poly (lactide-co-glycolide) of (M) over bar W 44 000, the pulsatile release was observed 38 days after the degradation starts. (C) 2000 Elsevier Science B.V. All rights reserved.