Measurement of drug release from microcarriers by microdialysis.
The purpose of this study was to examine the feasibility of the microdialysis sampling technique as a method to precisely and conveniently measure drug release from microcarrier systems such as liposomes and microspheres. Release of 5-fluorouracil (5-FU) from liposomes and microspheres was evaluated in vitro using microdialysis. Retrodialysis calibration using 5-chlorouracil (5-CU) was performed in conjunction with on-line HPLC analysis. At a microdialysis perfusate flow rate of 0.5 muL/min, concurrent 5-FU gain and 5-CU loss ranged from 72% to 75%, while concurrent 5-FU loss and 5-CU ranged from 69% to 71%. After calibration, simultaneous 5-FU release profiles were obtained by continuous microdialysis and discrete equilibrium dialysis sampling using a side-by-side diffusion apparatus. Release rates were characterized by a first-order release model. The release rate constants for a representative liposomal formulation were 0.30 and 1.85/h by microdialysis in the acceptor and donor compartments, respectively, and 0.39/h by equilibrium dialysis in the acceptor compartment. The calculated release rate constant determined by equilibrium dialysis in the donor compartment (1.98/h) agrees with that determined by microdialysis (1.85/h) when the resistance of the equilibrium dialysis membrane with associated first-order rate constant of transfer of 0.42/h is taken into account. Release profiles of 5-FU from a number of different liposome and microsphere formulations were determined. The results indicate that a convenient and reproducible characterization of drug release from various liposome and microsphere formulations is readily obtainable by microdialysis.
Hitzman
Cory J
CJ
Department of Pharmaceutics, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Wiedmann
Timothy S
TS
Dai
Haiqing
H
Elmquist
William F
WF
D015060:1,2-Dipalmitoylphosphatidylcholine; D000465:Algorithms; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry; D007700:Kinetics; D019344:Lactic Acid; D008081:Liposomes; D017551:Microdialysis; D008861:Microsomes; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D015203:Reproducibility of Results
D004337:Drug Carriers; D008081:Liposomes; D004364:Pharmaceutical Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D015060:1,2-Dipalmitoylphosphatidylcholine; D019344:Lactic Acid; D005472:Fluorouracil