Prediction of the in-vitro human skin permeability of nicorandil from animal data.
A method for estimating the in-vitro permeability of human skin to drugs, based on in-vitro permeation studies using animal skins, has been developed. The skins from hairless rats, guinea-pigs, dogs and pigs were used, with nicorandil and deionized water as model drug and solvent in a drug-donor compartment. Diffusion coefficients through the skin barrier, D, and partition coefficients from the drug-donor compartment to skin, K, of the drug, in each species, were calculated by curve-fitting the in-vitro permeation data to a diffusion equation describing the drug permeation through a homogeneous membrane, using a non-linear least squares method. Each barrier thickness, L, was measured microscopically from microtomed skin sections. A positive relationship was found between the skin permeability, Kp, and K value among the four species, but species differences in the D and L values were small in spite of the Kp values being different among the four species. A positive correlation was also observed between the calculated and experimental K values among the four species, and hence it was suggested that the main factor for the species difference in the skin permeability of nicorandil would be the difference in partitioning of the drug from vehicle to stratum corneum. As a result, it has become feasible to predict and estimate skin permeability of nicorandil in humans by substituting each parameter, extrapolated from the animal skin permeation data and partition experiments, in the diffusion equation.
Sato
K
K
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Sugibayashi
K
K
Morimoto
Y
Y
Omiya
H
H
Enomoto
N
N
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004285:Dogs; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D020108:Nicorandil; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D012995:Solubility; D013045:Species Specificity; D013552:Swine; D014867:Water
D008996:Monoamine Oxidase Inhibitors; D014867:Water; D009536:Niacinamide; D020108:Nicorandil