Abstract
The reliability of in vitro drug-release profiles of colloidal drug carriers using the dialysis membrane process was evaluated with a drug-selective electrode that measures the concentration profile of procaine hydrochloride (PrHy) in solution. This method allows for the measurement of actual concentration of drugs released from colloidal drug carriers since it does not require the separation of carriers from free drug molecules. The diffusion rate of PrHy was shown to increase with increasing molecular weight cut-off (MWCO) of the dialysis membrane and concentration difference between the dialysis membrane and bulk solution. These two findings demonstrated potential problems in the determination of drug-release profile due to the difficulty in measuring actual drug release profile of nanoparticles. The PrHy release from poly( N-isopropylacrylamide) (PNIPAM) microgels was shown to last 6 min, but the release in a 10 kDa MWCO dialysis cassette shows a release lasting over 1 h. This suggests that the dialysis membrane process introduces error in the determination of rapid release kinetics of nanoparticles. We showed that a drug-selective electrode provides a more robust method for quantifying the release kinetics of hydrophilic drugs.
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