Faster determination of membrane permeabilities without using the lag time method.
A new method of data analysis is presented that allows the determination of membrane permeabilities. The method is applicable to data obtained from a common experimental setup, in which drug dissolved in an inert donor gel diffuses through a membrane, initially void of drug, into a receiver for which sink conditions are maintained. The equations developed can also be used to predict the release of drug from these systems. Fick's Laws are solved, and the early time behavior of the mathematical solution is used to develop the analysis methods. Limitations of the model and their relations to experimental design are determined, and the method of application to experimental data is presented. The method is tested numerically using simulated data generated by a 1-d finite difference program that was used to numerically solve Fick's Laws, and also applied to in vitro human cadaver skin transdermal data for the drugs doxepin, imipramine and amitriptyline. It is concluded that this method can be applied to determine membrane permeabilities and diffusion coefficients with accuracy comparable to other experimental setups, such as lag time experiments and steady state experiments, but requiring experiments that can be significantly shorter.
Bellantone
Robert A
RA
Division of Pharmaceutics and Industrial Pharmacy, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 DeKalb Avenue, Brooklyn, NY 11201, USA. rbellant@liu.edu
Nicolettos
Nicos
N
Plakogiannis
Fotios M
FM
D015194:Diffusion Chambers, Culture / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008962:Models, Theoretical; D010539:Permeability / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D013678:Technology, Pharmaceutical / Q000379:methods*
D004364:Pharmaceutical Preparations