Effect of propylene glycol on ibuprofen absorption into human skin in vivo.
The objective was to assess the impact of propylene glycol (PG), a common cosolvent in topical formulations, on the penetration of ibuprofen into human skin in vivo. Drug uptake into the stratum corneum (SC), following application of saturated formulations containing from 0 to 100% v/v PG, was assessed by tape-stripping. Dermatopharmacokinetic parameters, characterizing drug amount in and diffusivity through the SC, were derived. The solubility behavior of ibuprofen in PG-water mixtures was carefully evaluated, as were a number of other physical properties. Ibuprofen delivery depended on the level of PG in the vehicle, despite all formulations containing the drug at equal thermodynamic activity. PG appeared to alter the solubility of ibuprofen in the SC (presumably via its own uptake into the membrane), the effect becoming more important as the volume fraction of cosolvent in the formulation increased. In summary, tape-stripping experiments, with careful interpretation, can reveal details of a drug's bioavailability in the skin following topical application and may be used to probe the mechanism(s) by which certain excipients influence local drug delivery.
Herkenne
Christophe
C
School of Pharmaceutical Sciences, University of Geneva, 30 quai E. Ansermet, CH-1211 Geneva 4, Switzerland.
Naik
Aarti
A
Kalia
Yogeshvar N
YN
Hadgraft
Jonathan
J
Guy
Richard H
RH
D000287:Administration, Topical; D000328:Adult; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004058:Diffusion; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009226:Myristates / Q000737:chemistry; D014677:Pharmaceutical Vehicles; D019946:Propylene Glycol / Q000494:pharmacology*; D012867:Skin / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects*; D012997:Solvents; D013816:Thermodynamics; D014783:Viscosity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009226:Myristates; D014677:Pharmaceutical Vehicles; D012997:Solvents; C008205:isopropyl myristate; D019946:Propylene Glycol; D007052:Ibuprofen