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

Research output: Contribution to journalArticle

Abstract

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-hour uptake and clearance over the subsequent 22 hours), 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.
LanguageEnglish
Pages167-172
Number of pages6
JournalInternational Journal of Pharmaceutics
Volume541
Early online date17 Feb 2018
DOIs
StatusPublished - 25 Apr 2018

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Metronidazole
Cornea
Skin
Pharmaceutical Preparations
Biological Availability
Volunteers
Pharmacokinetics

Keywords

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

Cite this

Pedon de Araujo, T., Moura Fittipaldi, I., Galindo Bedor, D. C., Ludna Duarte, M., Cordery, S., Guy, R., ... Bastos Leal, L. (2018). Topical bio(in)equivalence of metronidazole formulations in vivo. International Journal of Pharmaceutics, 541, 167-172. DOI: 10.1016/j.ijpharm.2018.02.032

Topical bio(in)equivalence of metronidazole formulations in vivo. / Pedon de Araujo, Thalita; Moura Fittipaldi, Isabelle; Galindo Bedor, Danilo Cesar; Ludna Duarte, Maira; Cordery, Sarah; Guy, Richard; Delgado-Charro, Maria; Pereira de Santana, Davi; Bastos Leal, Leila.

In: International Journal of Pharmaceutics, Vol. 541, 25.04.2018, p. 167-172.

Research output: Contribution to journalArticle

Pedon de Araujo, T, Moura Fittipaldi, I, Galindo Bedor, DC, Ludna Duarte, M, Cordery, S, Guy, R, Delgado-Charro, M, Pereira de Santana, D & Bastos Leal, L 2018, 'Topical bio(in)equivalence of metronidazole formulations in vivo' International Journal of Pharmaceutics, vol 541, pp. 167-172. DOI: 10.1016/j.ijpharm.2018.02.032
Pedon de Araujo T, Moura Fittipaldi I, Galindo Bedor DC, Ludna Duarte M, Cordery S, Guy R et al. Topical bio(in)equivalence of metronidazole formulations in vivo. International Journal of Pharmaceutics. 2018 Apr 25;541:167-172. Available from, DOI: 10.1016/j.ijpharm.2018.02.032
Pedon de Araujo, Thalita ; Moura Fittipaldi, Isabelle ; Galindo Bedor, Danilo Cesar ; Ludna Duarte, Maira ; Cordery, Sarah ; Guy, Richard ; Delgado-Charro, Maria ; Pereira de Santana, Davi ; Bastos Leal, Leila. / Topical bio(in)equivalence of metronidazole formulations in vivo. In: International Journal of Pharmaceutics. 2018 ; Vol. 541. pp. 167-172
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