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  • Title: Influence of the microencapsulation method and peptide loading on poly(lactic acid) and poly(lactic-co-glycolic acid) degradation during in vitro testing.
    Author: Witschi C, Doelker E.
    Journal: J Control Release; 1998 Feb 12; 51(2-3):327-41. PubMed ID: 9685930.
    Abstract:
    Three methods were used, namely spray drying, w/o/w solvent evaporation and the aerosol solvent extraction system (ASES), for the preparation of microparticles having the same size range, to study the influence of the preparation method on polymer degradation in vitro (PBS, 37 degrees C, one month). The following five polymers of the biodegradable poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) group were selected: L-PLA, MW 81 200; DL-PLGA 75:25, MW 64-300; DL-PLGA 50:50 MW 52 600; DL-PLGA 50:50 MW 14 500, AND DL-PLGA 50:50, MW 3400, to prepare drug-free and drug-loaded microparticles. Tetracosactide was selected as model peptide. When microparticles were prepared by solvent evaporation, the mean diameter and, more markedly, the drug encapsulation efficiency tended to decrease when decreasing the molecular weight and increasing the proportion of glycolic acid in the polymer. In contrast, no direct influence of the polymer nature on these parameters was observed in spray dried microparticles. Polymer degradation was heterogenous in L-PLA and DL-PLGA 75:25 microparticles and was not influenced by the presence of the drug at a nominal loading of 1% (w/w), when prepared by the three methods (note that with ASES, only L-PLA could be used for microencapsulation). In batches made of DL-PLGA 50:50 MW 52 600, the degradation rate decreased slightly when increasing the drug loading. Only in the case of DL-PLGA 50:50 MW 14 500, the polymer degradation rate for spray dried microparticles was higher compared to that for microparticles prepared by the w/o/w solvent evaporation method. Generally, the degradation rates of the different microparticles followed the expected order: L-PLA<DL-PLGA 75:50<DL-PLGA 50:50(Mw 52 600)<DLPLGA 50:50 (a mixture of MW 52 600 and MW 3400). Polymer degradation was homogenous in DL-PLGA 50:50 microparticles. Decreasing the molecular weight of DL-PLGA 50:50 from 52 600 to 14 500 did not result in accelerated polymer degradation.
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