3 rd Conference on
“Innovation in Drug Delivery: Advances in Local Drug Delivery”
22-25 September, 2013
PISA (Italy)
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Deadline: 1 March, 2013
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Please return completed abstract form by 1 March, 2013

POTENTIAL IMPACT OF PERFECT SINK CONDITIONS ON
PLGA MICROPARTICLE DEGRADATION
Céline Delplace, 1,2 Diana Klose, 1,2,3 Juergen Siepmann 1,2
1 University Lille Nord de France, College of Pharmacy,
3 Rue du Prof. Laguesse, FR-59006 Lille, France
2 INSERM U 1008, Controlled Drug Delivery Systems and
Biomaterials, 3 Rue du Prof. Laguesse, FR-59006 Lille, France
3 Freie Universitaet Berlin, College of Pharmacy, Kelchstr. 31,
DE-12169 Berlin, Germany
E-mail: celine.delplace-3@univ-lille2.fr
Purpose: To better understand the potential impact of the maintenance of perfect sink conditions during drug release measurements from PLGA-based microparticles on the observed release patterns and polymer degradation.
Methods: Differently sized, highly porous, carbamazepine- and ibuprofen-loaded PLGA microparticles were prepared by a W/O/W emulsion solvent evaporation technique. Drug release into phosphate buffer pH 7.4 was measured under perfect sink conditions and the pH of the bulk fluid was monitored. DSC and SEC were used to characterize polymer degradation.
Results: The decrease in the average polymer molecular weight and glass transition temperature of the PLGA microparticles were strongly affected by the bulk fluid’s volume. In the case of the poorly watersoluble drug carbamazepine, much lower “microparticle mass:phosphate buffer volume” ratios were required to maintain perfect sink conditions: 0.5 mg/ml compared to 10 mg/ml in the case of ibuprofen. The lower ratios resulted in stable pH values within the bulk fluid, slower PLGA degradation and, thus, lower drug release rates. For instance, the average polymer molecular weight of large microparticles decreased from 35 kDa to 17 kDa and 10 kDa after 10 d exposure to phosphate buffer pH 7.4 in the case of carbamazepine and ibuprofen. In the same time frame, 40 and 100% drug were released, respectively.
Conclusion: Great care has to be taken when defining the conditions for in vitro drug release measurements from PLGA-based microparticles, avoiding potentially artificial conditions for polymer degradation.