PLGA erosion: solubility- or diffusion-controlled?
OBJECTIVE
To calculate the degradation time-dependent formation of water-soluble PLGA oligomers and to evaluate the relation between calculated oligomer formation and actual erosion of a PLGA-based delivery system. A proper model of the erosion process would be expected to facilitate forecasting of drug release profiles from PLGA matrices due to the close relationship of erosional mass loss and drug release described in the literature.


METHODS
The molecular weight distribution (MWD), degradation and erosion behaviour of PLGA were characterized by gel permeation chromatography.


RESULTS
PLGA was characterized by a lognormal distribution of mass fractions of individual molecular weights. Implementation of the pseudo-first-order reaction kinetics into the MWD function facilitated calculating the formation of water-soluble oligomers during degradation. The calculated soluble oligomer formation agreed excellently with measured erosional mass loss of a PLGA matrix in aqueous buffer, which suggested that the bulk erosion process was solely controlled by the kinetic of the formation of soluble oligomers and thus solubility-controlled and not diffusion-limited as conventionally assumed.


CONCLUSIONS
The accurately calculated formation of soluble PLGA oligomers was in excellent agreement with the actual erosional mass loss of a PLGA matrix, suggesting that bulk erosion of PLGA represents a degradation-controlled dissolution process.
Körber
Martin
M
College of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, 12169, Berlin, Germany. koerberm@zedat.fu-berlin.de
D002850:Chromatography, Gel; D004058:Diffusion; D019344:Lactic Acid / Q000737:chemistry*; D008962:Models, Theoretical; D008970:Molecular Weight; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility
D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid