Topical bio(in)equivalence of metronidazole formulations in vivo

Thalita Pedon de Araujo, Isabelle Moura Fittipaldi, Danilo Cesar Galindo Bedor, Maira Ludna Duarte, Sarah Cordery, Richard Guy, Maria Delgado-Charro, Davi Pereira de Santana, Leila Bastos Leal

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The topical bioavailabilities of metronidazole from a commercially available ‘reference’ product (Rozex®) and two extemporaneous test formulations were compared. With the reference drug product, a full skin pharmacokinetic profile, in vivo in human volunteers (following a 6-h uptake and clearance over the subsequent 22 h), was obtained using an improved stratum corneum (SC) sampling procedure. Then, a two-time point SC sampling method enabled the bio(in)equivalence of the test formulations to Rozex® to be evaluated. One test formulation was shown to be bioequivalent to Rozex®, both for uptake and clearance, whereas the other (more viscous and less spreadable) formulation was not. The delivery of metronidazole into the underlying viable epidermal tissue from Rozex® and from the equivalent test formulation was 2.5 to 3.5-fold higher than that from the inequivalent extemporaneous vehicle. The results highlight that the quantitative composition of a formulation, as well as its physical properties that influence events that take place at the vehicle-skin interface, can have a dramatic impact on the delivery of drug into the SC and subsequently to the viable skin layers below. The reproducible, sensitive and facile in vivo methodology employed may prove of particular value where regulatory approval of generic formulations lacks objective rigour.

Original languageEnglish
Pages (from-to)167-172
Number of pages6
JournalInternational Journal of Pharmaceutics
Issue number1-2
Early online date17 Feb 2018
Publication statusPublished - 25 Apr 2018


  • topical bioavailability
  • skin pharmacokinetics
  • stratum corneum sampling in vivo
  • metronidazole
  • skin
  • topical bioequivalence


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