Comparative Evaluation of In Vitro Drug Release Methods Employed for Nanoparticle Drug Release Studies

摘要

The aim of the present study was to experimentally compare the attributes, drawbacks, and limitations of the most commonly employed in vitro drug release test methods for nanoparticle systems and to explore the possibility of one method being adopted as a standard for quality control of nanoparticle-based products. Three in vitro drug release test methods, i.e., direct addition, dialysis bag, and low-pressure ultrafiltration, were employed for evaluation of drug release from tamoxifen-loaded poly(lactic-co-glycolic acid) nanoparticles. Relevant operational characteristics of each test method were compared. Drug release data were fitted in different release kinetics models, i.e., zero order, first order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas. The coefficient of determination (R2), release rate constant (k), and release exponent (n) values were calculated. The direct addition method showed rapid initial drug release, whereas a slow release rate was observed in the dialysis bag method. Results of the low-pressure ultrafiltration method were consistent with the direct addition method and various operational characteristics were more realistic than the other two methods. Overall, the findings support that low-pressure ultrafiltration can be considered as a standard regulatory test method for in vitro release of nanoparticle-based formulations.