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Eur J Pharm Sci. 2007 Nov;32(3):209-15. Epub 2007 Aug 11.

Enhancement of skin penetration of vitamin K using monoolein-based liquid crystalline systems.

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Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, 14040-930, Ribeirão Preto, SP, Brazil.


Application of vitamin K (vitK) to the skin has been used for suppression of pigmentation and resolution of bruising. However, there is no report concerning the extent of its penetration in the skin. In this study, we investigated the in vitro skin penetration and transdermal delivery of vitK, and whether these parameters may be enhanced by lipid-based drug delivery systems. The lipid formulation used in this study contains monoolein (MO), which is structured as a liquid crystalline phase, named hexagonal phase. The skin penetration of vitK was assessed in vitro using porcine ear skin mounted in a Franz diffusion cell. VitK (2.5%, w/w) was incorporated in either of three formulations: liquid vaseline, MO-based hexagonal phase gel (MO-vitK-water at 77.5/2.5/20, w/w/w) and MO-based nanodispersion of hexagonal phase (MO-vitK-poloxamer-water at 15/2.5/0.9/81.6, w/w/w/w). When vaseline was used, vitK was delivered mainly to the stratum corneum (SC): 9.50+/-0.97 microg/cm(2) of vitK was delivered to the SC at 12 h post-application, whereas 4.90 +/- 1.28 microg/cm(2) of vitK was delivered to the epidermis (E)+dermis (D) at the same time point. The hexagonal phase gel and the nanodispersion delivered approximately 2 times more vitK to the SC and 2.0-3.7 times more vitK to the [E+D] than the vaseline solution. The nanodispersion (but not the gel) also increased the transdermal delivery of vitK at 9 h ( approximately 3-fold increase). These results demonstrate that the topical delivery of vitK incorporated in a lipophilic vehicle is small, but it may be enhanced by MO-based systems, which might be useful to increase the effectiveness of topical vitK therapy.

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