Film drying and complexation effects in the simultaneous skin permeation of ketoprofen and propylene glycol from simple gel formulations

Int J Pharm. 2006 Jan 13;307(2):251-7. doi: 10.1016/j.ijpharm.2005.10.014. Epub 2005 Nov 14.

Abstract

This work investigated the simultaneous permeation of ketoprofen and propylene glycol (PG) across pig ear skin from simple gel formulations administered under simulated in-use conditions. The aims were to quantify rates of permeation of both solvent and active, probe the effects of formulation drying and gain insight into drag/complexation interactions. Simple 3-component gels were formulated using a fixed amount of ketoprofen and hydroxypropyl cellulose thickener with decreasing content of solvent propylene glycol. Multiple finite (5 mg x 15 mg) doses were massaged over 24h into full thickness pig ear skin in vertical Franz-type diffusion cells. The permeation of ketoprofen was inversely proportional to the content of PG, whereas the permeation of PG was directly proportional, although the amount of PG permeated was always greater than ketoprofen, even from the driest gel practically achievable. In this state, the molar ratio of PG/ketoprofen was approximately 12, suggesting that this number of PG molecules constitutes the solvation cage of ketoprofen. Dragging/pulling effect extends throughout the skin and into the receptor compartment and probably the system, in an in vivo situation. Although PG may represent a worse case scenario given its well-documented skin permeation enhancement properties, it is probable that other solvents exert a similar effect on solutes across skin. A drying film will behave in different ways depending on the nature of both the thickener and solvent, where the outcomes are not readily predictable. It is important to account for the fate of all species administered from a topical formulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Cellulose / analogs & derivatives
  • Cellulose / chemistry
  • Cellulose / metabolism
  • Chemistry, Pharmaceutical
  • Desiccation
  • Drug Combinations
  • Gels*
  • In Vitro Techniques
  • Ketoprofen / chemistry
  • Ketoprofen / metabolism*
  • Permeability
  • Propylene Glycol / chemistry
  • Propylene Glycol / metabolism
  • Skin Absorption*
  • Solvents / chemistry
  • Solvents / metabolism*
  • Swine
  • Time Factors

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Combinations
  • Gels
  • Solvents
  • Propylene Glycol
  • Cellulose
  • Ketoprofen
  • hydroxypropylcellulose