In vitro-in vivo correlation in skin permeation

Pharm Res. 2014 Feb;31(2):394-400. doi: 10.1007/s11095-013-1169-2. Epub 2013 Aug 14.


Purpose: In vitro skin permeation studies have been used extensively in the development and optimisation of delivery of actives in vivo. However, there are few reported correlations of such in vitro studies with in vivo data. The aim of this study was to investigate the skin permeation of a model active, niacinamide, both in vitro and in vivo.

Methods: Conventional diffusion cell studies were conducted in human skin to determine niacinamide permeation from a range of vehicles which included dimethyl isosorbide (DMI), propylene glycol (PG), propylene glycol monolaurate (PGML), N-methyl 2-pyrrolidone (NMP), Miglyol 812N® (MG), and mineral oil (MO). Single, binary or ternary systems were examined. The same vehicles were subsequently examined to investigate niacinamide delivery in vivo. For this proof-of-concept study one donor was used for the in vitro studies and one volunteer for the in vivo investigations to minimise biovariability. Analysis of in vitro samples was conducted using HPLC and in vivo uptake of niacinamide was evaluated using Confocal Raman spectroscopy (CRS).

Results: The amount of niacinamide permeated through skin in vitro was linearly proportional to the intensity of the niacinamide signal determined in the stratum corneum in vivo. A good correlation was observed between the signal intensities of selected vehicles and niacinamide signal intensity.

Conclusions: The findings provide further support for the use of CRS to monitor drug delivery into and across the skin. In addition, the results highlight the critical role of the vehicle and its disposition in skin for effective dermal delivery.

MeSH terms

  • Administration, Cutaneous
  • Drug Delivery Systems / methods
  • Excipients / chemistry
  • Excipients / metabolism
  • Female
  • Humans
  • Isosorbide / analogs & derivatives
  • Isosorbide / chemistry
  • Isosorbide / metabolism
  • Laurates / chemistry
  • Laurates / metabolism
  • Mineral Oil / chemistry
  • Mineral Oil / metabolism
  • Niacinamide / chemistry*
  • Niacinamide / metabolism*
  • Permeability
  • Pharmaceutical Vehicles / chemistry*
  • Pharmaceutical Vehicles / metabolism*
  • Propylene Glycol / chemistry
  • Propylene Glycol / metabolism
  • Propylene Glycols / chemistry
  • Propylene Glycols / metabolism
  • Pyrrolidinones / chemistry
  • Pyrrolidinones / metabolism
  • Skin / metabolism*
  • Skin Absorption / physiology
  • Solubility
  • Solvents / chemistry
  • Solvents / metabolism


  • Excipients
  • Laurates
  • Pharmaceutical Vehicles
  • Propylene Glycols
  • Pyrrolidinones
  • Solvents
  • Niacinamide
  • propyleneglycol monolaurate
  • Propylene Glycol
  • Mineral Oil
  • 2-pyrrolidone
  • 2,5-dimethylisosorbide
  • Isosorbide