Towards more realistic in vitro release measurement techniques for biodegradable microparticles.
OBJECTIVE
To better understand the importance of the environmental conditions for drug release from biodegradable microparticles allowing for the development of more appropriate in vitro release measurement techniques.


METHODS
Propranolol HCl diffusion in various agarose gels was characterized by NMR and UV analysis. Fick's law was used to theoretically predict the mass transport kinetics. Drug release from PLGA-based microparticles in such agarose gels was compared to that measured in agitated bulk fluids ("standard" method).


RESULTS
NMR analysis revealed that the drug diffusivity was almost independent of the hydrogel concentration, despite of the significant differences in the systems' mechanical properties. This is due to the small size of the drug molecules/ions with respect to the hydrogel mesh size. Interestingly, the theoretically predicted drug concentration-distance-profiles could be confirmed by independent experiments. Most important from a practical point of view, significant differences in the release rates from the same batch of PLGA-based microparticles into a well agitated bulk fluid versus a semi-solid agarose gel were observed.


CONCLUSIONS
Great care must be taken when defining the in vitro conditions for drug release measurements from biodegradable microparticles. The obtained new insight can help facilitating the development of more appropriate in vitro release testing procedures.
Klose
D
D
College of Pharmacy, JE 2491, University of Lille, 3 rue du Professeur Laguesse, 59006, Lille, France.
Azaroual
N
N
Siepmann
F
F
Vermeersch
G
G
Siepmann
J
J
D001672:Biocompatible Materials / Q000737:chemistry*; D001692:Biological Transport; D004337:Drug Carriers / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D008962:Models, Theoretical; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011433:Propranolol / Q000008:administration & dosage / Q000493:pharmacokinetics; D012685:Sepharose / Q000737:chemistry*; D013499:Surface Properties
D001672:Biocompatible Materials; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012685:Sepharose; D011433:Propranolol