title: Mathematical model to predict skin concentration of drugs: toward utilization of silicone membrane to predict skin concentration of drugs as an animal testing alternative.
abstract: OBJECTIVE
  To calculate the skin concentration of active ingredients in cosmetics and topical pharmaceuticals using silicone membrane permeation.
  
  
  METHODS
  A series of parabens were used as model ingredients. Skin concentration of parabens was calculated using silicone membrane permeability. Their partition coefficient from formulations to the silicone membrane was determined by the membrane permeation profiles, and used to calculate their silicone membrane concentration, under an assumption that the membrane is one homogenous diffusion layer. The same procedure was applied for hairless rat skin.
  
  
  RESULTS
  The calculated concentration of parabens in silicone membrane was very close to their observed values. However, the skin concentration calculated by skin permeability was not similar to the observed concentration. Re-calculation was performed under the assumption that the skin consists of two diffusion layers. This modification using permeation data through full-thickness and stripped skin enabled precise prediction of the skin concentration of parabens. In addition, the partition coefficient to the silicone membrane was useful to estimate their skin concentration.
  
  
  CONCLUSIONS
  Ingredient concentration in skin can be precisely predicted using diffusion equations and partition coefficients through permeation experiments using a silicone membrane. The calculated in-skin concentration is useful for formulation studies of cosmetics and topical pharmaceuticals.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan. sugib@josai.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugibayashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Todo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oshizaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Owada
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D008297:Male; D008567:Membranes, Artificial; D015233:Models, Statistical; D008962:Models, Theoretical; D010226:Parabens / Q000493:pharmacokinetics*; D004364:Pharmaceutical Preparations; D010599:Pharmacokinetics; D051381:Rats; D054772:Rats, Hairless; D012828:Silicones / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D008567:Membranes, Artificial; D010226:Parabens; D004364:Pharmaceutical Preparations; D012828:Silicones