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.[1]References
- Measurement of drug release from microcarriers by microdialysis. Hitzman, C.J., Wiedmann, T.S., Dai, H., Elmquist, W.F. Journal of pharmaceutical sciences. (2005) [Pubmed]
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