In vitro Skin Permeability of Different Terbinafine Hydrochloride Formulations

Abstract

The objectives of the study are to determine the in vitro permeability of different terbinafine hydrochloride formulations through human skin and to measure the respective concentrations of each formulation within the exposed skin tissue. The permeation of three commercially available 1% terbinafine hydrochloride formulations and two terbinafine hydrochloride solutions of 10 and 20 mg/ml through human skin was investigated using an in vitro continuous flow-through perfusion system. The terbinafine hydrochloride retained in the skin was extracted and analysed. The terbinafine hydrochloride from the different formulations readily diffused into the skin tissue. However, no flux values for any of the terbinafine hydrochloride formulations through the skin into the receptor fluid were found. The mean terbinafine hydrochloride concentrations in the skin after 24 h exposure to the three commercial formulations were 3.589, 1.590 and 4.219 ug/ml respectively. The mean terbinafine hydrochloride concentrations in the skin after 24 h of exposure to the terbinafine hydrochloride solutions (PBS/Methanol 1:1) of 10 and 20 mg/ml were 85.280 and 154.680 ug/m] respectively. The mean terbinafine hydrochloride concentration in the skin exposed to the 10 mg/ml PBS/Methanol solution was higher than those from the three commercial formulations. Terbinafine seems to accumulate in skin/bind to the skin, rather than to diffuse through the skin into the receptor compartment. This unique pharmacokinetic property of terbinafine hydrochloride may enhance its efficacy as topical antifungal and reduce systemic side effects.Dermal and transdermal drug delivery serve as an attractive alternative to conventional drug delivery methods. Topical administration of drugs can be used to achieve systemic or local effects. The barrier properties and the subsequent impermeability of the skin are a considerable problem in the delivery of active compounds both to and through skin. The pharmaceutical industry is therefore investing everincreasing amounts of resources on the development of new products that are able to overcome the barrier properties of the skin (l). Even though the skin is very accessible for drug administration and research, some aspects of transdermal drug penetrations remain unknown.Due to modem high-throughput technologies large numbers of potential drugs are produced by parallel synthesis and combinatorial chemistry. The pharmaceutical industry therefore requires rapid and accurate methods to screen drug leads for tissue permeability potential in the early stages of drug discovery. In vivo human dermal studies are not always feasible due to the invasiveness of biopsies

A Quantitative MALDI-MSI Study of the Movement of Molecules in Biological Systems

“…From the image it can be seen that the terbinafine signal appeared to be localised solely to the epidermal layer, with no penetration within the dermal region. The absence of the drug in the deeper layer of the skin was as expected considering the high lipophilicity and keratophilicity of the molecule, which leads to its accumulation solely onto the epidermal layer (Pretorius et al, 2008).…”

Vascular Endothelial Growth Factor and E-Nitric Oxide Synthase-Mediated Regenerative Response Occurring upon Autologous and Heterologous Bone Grafts

“…In our study, the expression of BSP resulted higher in eAB sample, demonstrating new bone formation and stronger remodeling than in sites treated with intraoral autologous bone or heterologous bone particles. The positive staining of BSP suggests that host cells surrounding and invading the graft follow the osteogenic differentiation pathway (42)(43)(44). The results support the hypothesis that bone regeneration proceeds up to six months after sinus lifting, thus further increasing bone quality and volume.…”