title: Fixed-Combination Gels of Adapalene and Benzoyl Peroxide Provide Optimal Percutaneous Absorption Compared to Monad Formulations of These Compounds: Results from Two In Vitro Studies.
abstract: BACKGROUND
  Adapalene 0.1%/benzoyl peroxide 2.5% (0.1% A/BPO) and adapalene 0.3%/BPO 2.5% (0.3% A/BPO) gels are fixed-combination options for the topical treatment of acne. However, the active compounds of these combinations are also available as monads, to be used in association or as monotherapy. These two in vitro studies determined the effect of different treatment regimens on the percutaneous absorption of adapalene (0.1% and 0.3%) gels and BPO 2.5% gel in ex vivo human skin.
  
  
  METHODS
  In vitro percutaneous absorption studies were conducted using full-thickness human skin from six donors. Treatment regimens included the application of 0.1% A/BPO, 0.3% A/BPO, or four free-combination regimens of the monads. Skin samples were incubated for 24 h. Concentrations of adapalene and BPO equivalent (BPO-eq) (i.e. benzoic acid after chemical transformation of BPO) were measured using high-performance liquid chromatography. Comparison of regimens was performed using a bioequivalence criterion (estimated ratio bewteen 0.8 and 1.25).
  
  
  RESULTS
  The fixed combination 0.3% A/BPO regimen demonstrated more than three times higher absorption of adapalene versus the fixed-combination 0.1% A/BPO. Based on the bioequivalence acceptance criterion, all four free-combination regimens were different from 0.1% A/BPO and 0.3% A/BPO, with higher adapalene release delivered by the fixed combinations versus the free combinations. For BPO-eq, the results showed that the free-combination regimens where adapalene 0.1% was applied first were different from 0.1% A/BPO, with lower BPO-eq release delivered by these regimens compared to the fixed combination. The regimen adapalene 0.3% for 10 h followed by BPO 2.5% delivered lower BPO-eq release compared to the fixed combination.
  
  
  CONCLUSIONS
  The fixed-combination A/BPO gels provide optimal percutaneous absorption of the active compounds compared to free combinations of adapalene 0.1%, adapalene 0.3%, and BPO 2.5%. The higher concentration of adapalene in the 0.3% A/BPO gel and the resulting higher absorption may explain higher clinical efficacy.
authors.affiliation: Galderma R&D, Les Templiers, 2400 Route des Colles, BP87, 06902, Sophia Antipolis, France. hanan.osman-ponchet@galderma.com.
authors.forename: Hanan
authors.initials: H
authors.lastname: Osman-Ponchet
authors.affiliation: Galderma R&D, Les Templiers, 2400 Route des Colles, BP87, 06902, Sophia Antipolis, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Sevin
authors.affiliation: Galderma R&D, Les Templiers, 2400 Route des Colles, BP87, 06902, Sophia Antipolis, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gaborit
authors.affiliation: Galderma R&D, Les Templiers, 2400 Route des Colles, BP87, 06902, Sophia Antipolis, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wagner
authors.affiliation: Galderma R&D, Les Templiers, 2400 Route des Colles, BP87, 06902, Sophia Antipolis, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Poncet
keywords: Adapalene/benzoyl peroxide gel; Fixed combination; In vitro; Optimal percutaneous absorption