A New Method for Evaluating Actual Drug Release Kinetics of Nanoparticles inside Dialysis Devices via Numerical Deconvolution.
Nanoparticle formulations have found increasing applications in modern therapies. To achieve desired treatment efficacy and safety profiles, drug release kinetics of nanoparticles must be controlled tightly. However, actual drug release kinetics of nanoparticles cannot be readily measured due to technique difficulties, although various methods have been attempted. Among existing experimental approaches, dialysis method is the most widely applied one due to its simplicity and avoidance of separating released drug from the nanoparticles. Yet this method only measures the released drug in the medium outside a dialysis device (the receiver), instead of actual drug release from the nanoparticles inside the dialysis device (the donor). Thus we proposed a new method using numerical deconvolution to evaluate actual drug release kinetics of nanoparticles inside the donor based on experimental release profiles of nanoparticles and free drug solution in the receptor determined by existing dialysis tests. Two computer programs were developed based on two different numerical methods, namely least square criteria with prescribed Weibull function or orthogonal polynomials as input function. The former was used for all analyses in this work while the latter for verifying the reliability of the predictions. Experimental data of drug release from various nanoparticle formulations obtained from different dialysis settings and membrane pore sizes were used to substantiate this approach. The results demonstrated that this method is applicable to a broad range of nanoparticle and microparticle formulations requiring no additional experiments. It is independent of particle formulations, drug release mechanisms, and testing conditions. This new method may also be used, in combination with existing dialysis devices, to develop a standardized method for quality control, in vitro-in vivo correlation, and for development of nanoparticles and other types of dispersion formulations.
AP-CAD Inc., Toronto, Ontario, Canada, M2N 3X2.
Yousheng
Y
Zhou
Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada M5S 2S2.
Chunsheng
C
He
Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada M5S 2S2.
Kuan
K
Chen
School of Information Science and Engineering, East China University of Science and Technology, Shanghai, China, 200237.
Jieren
J
Ni
School of Pharmacy, Jinan University, Guangzhou, China, 510632.
Yu
Y
Cai
Prinston Pharmaceutical Inc., Cranbury, NJ 08512, USA.
Xiaodi
X
Guo
Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada M5S 2S2. Electronic address: xywu@phm.utoronto.ca.
Xiao Yu
XY
Wu
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003956:Dialysis / Q000379:methods*; D065546:Drug Liberation; D007700:Kinetics; D053758:Nanoparticles; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D015203:Reproducibility of Results; D012984:Software
D004364:Pharmaceutical Preparations
Nanoparticles; actual release profiles inside the dialysis device; dialysis experiments; drug release kinetics; numerical deconvolution