Improved Bioequivalence Assessment of Topical Dermatological Drug Products Using Dermatopharmacokinetics

• Published in: Pharmaceutical research 2009-02, Vol.26 (2), p.316-328
• Main Authors: N'Dri-Stempfer, Berthe, Navidi, William C, Guy, Richard H, Bunge, Annette L
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Adult; Bioavailability; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chemistry, Pharmaceutical; Dermatologic Agents - administration & dosage; Dermatologic Agents - pharmacokinetics; Dermatology; dermatopharmacokinetics; Drug delivery systems; econazole; Econazole - administration & dosage; Econazole - pharmacology; Female; General pharmacology; Humans; Male; Medical Law; Medical sciences; Middle Aged; Models, Biological; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Reproducibility of Results; Research Paper; Skin; Skin - metabolism; Skin Absorption; stratum corneum; tape stripping; Therapeutic Equivalency; topical drug bioequivalence; Young Adult
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-008-9742-9

Purpose A dermatopharmacokinetic (DPK) approach, in which drug levels in the stratum corneum (SC) are measured as a function of time post-application and post-removal of the product using tape-strip sampling in vivo in humans, has been considered for the comparative assessment of topical bioavailability. Its application to-date has been limited by contradictory results and concerns that variability in the method necessitates large numbers of treatment sites and volunteers. The objective of this study was to test whether a revised protocol could better assess bioequivalence. Methods A blinded study of three 1% econazole nitrate cream products, for which the SC is the site of action, was conducted to examine several modifications to the DPK methodology. In addition to protocol changes designed to reduce experimental variability, bioequivalence was assessed at a single uptake time and a single clearance time measured in duplicate in each subject. Results Conclusive determinations of bioequivalence were achieved with only four treatment sites per product in each of 14 volunteers, which was less than one-third the number required in a previous DPK investigation. Conclusions Comparative bioequivalence can be assessed conclusively with fewer treatment sites in fewer subjects with robust methods that should be less sensitive to inter-laboratory differences.