Topical bio(in)equivalence of metronidazole formulations in vivo

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.</p

New Oils for Cosmetic O/W Emulsions: In Vitro/In Vivo Evaluation

The aim of this study was to design new cosmetic formulations containing oils from catolé, licuri and spent coffee grounds, and to evaluate their immediate and long-term effects on skin barrier function and skin hydration. Nonionic oil-in-water (o/w) emulsions were prepared and physicochemically characterized. The effects of the formulations were assessed by volunteers and by measuring the water content of the epidermis (WCE) and transepidermal water loss (TEWL) both two hours and 20 days after daily application. The irritation potential was evaluated using three different methods: the Hen’s egg chorioallantoic membrane test (HET-CAM); the observation of undesirable effects after skin formulation application, and by using the L*a*b* system to verify changes in skin coloring. The results obtained showed that the formulations containing 10% of these oils presented promising characteristics in the improvement of hydration and skin barrier function when compared to the baseline values and with the placebo cream. According to the sensory evaluation performed, all creams were found to have great acceptability