Topical bio(in)equivalence of metronidazole formulations in vivo.
Int J Pharm
; 541(1-2): 167-172, 2018 Apr 25.
Article
en En
| MEDLINE
| ID: mdl-29462685
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-h uptake and clearance over the subsequent 22â¯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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Absorción Cutánea
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Disponibilidad Biológica
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Tecnología Farmacéutica
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Medicamentos Genéricos
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Metronidazol
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Int J Pharm
Año:
2018
Tipo del documento:
Article
País de afiliación:
Brasil