Ketoprofen-poly(D,L-lactic-co-glycolic acid) microspheres: influence of manufacturing parameters and type of polymer on the release characteristics

The effect of manufacturing parameters on the size and drug-loading of keto profen-containing biodegradable and biocompatible poly(DL-lactic-co-glycoli c acid) (PLGA) microspheres prepared by the solvent evaporation method was investigated. For both drug-free and drug-loaded microspheres, smaller micr ospheres with a narrower size distribution were obtained when the stirring rate or the volume of the organic phase was increased. Incorporation of ket oprofen was found to increase with increasing volume of the organic phase a nd decreasing pH of the aqueous phase, but was independent of the acidity a nd the inherent viscosity of the PLGA used. The biphasic release profile of ketoprofen from the microspheres was dependent on the type of PLGA as well as the size and drug-loading, two parameters governed by the manufacturing process. The first burst effect was found to increase with the drug conten t, reduction of size of the microspheres and increasing inherent viscosity of the matrix, whereas acidity of the PLGA had no effect on the release of this acidic drug. A vigorous first burst effect was associated with reduced sustained delivery of ketoprofen, the rate of the delayed release phase be ing dependent on the inherent viscosity of the matrix, the size, the payloa d and the pH during preparation of the microspheres. Thus, by selection of the manufacturing parameters and the type of PLGA, it is possible to design a controlled drug delivery system for the prolonged release of ketoprofen, improving therapy by possible reduction of time intervals between peroral adminstration and reduction of local gastrointestinal side effects.