Optimization of skin permeation and distribution of ibuprofen by using nanostructures (coagels) based on alkyl vitamin C derivatives

SAINO, VERONICA; MONTI DANIELA; BURGALASSI, SUSY; TAMPUCCI S; PALMA SANTIAGO; ALLEMANDI DANIEL; CHETONI PATRIZIA

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

ELSEVIER SCIENCE BV

Año: 2010 vol. 76 p. 443 - 449

0939-6411

In this investigation two vitamin C-based -6-O-ascorbic acid esters (ASC12 and ASC16), able to form liquid–crystal structures (coagels) was evaluated for their potential usefulness to promote the permeation and distribution of ibuprofen (IBU). Two coagel formulations and the same coagels added of polyethylene glycol (PEG-400) were assayed in comparison with a commercial product (Arfen) by using hairless rat skin as model. The ASC16 and ASC12 derivatives gave rise to stable supramolecular assemblies in water and in water/ PEG mixtures (coagels), allowing the solubilization of IBU (0.85%) and producing a IBU controlled release systems, as evidenced by the dynamic dialyse test: the n values were near 1.0, indicative of a linear kinetic, for all coagel formulations, except for the ASC12PEG/C formulation (n = 1.51). Our results evidenced the enhancement activity of coagels and the synergic effect of the combination with PEG: all coagels showed a higher amount of IBU permeated through the skin compared to commercial Arfen with an enhancement factor of 52.94 and 21.53 for ASC12PEG/C and ASC16/C respectively. Otherwise, coagels formulations appeared to produce a low IBU depot in the skin and in the same order of magnitude in epidermis and derma, in spite of significant increase of IBU cutaneous permeation. The positive synergic effect of the coagel–PEG mixtures was demonstrated by the high amount of IBU accumulated in the upper skin layers. The effect of the coagels on the IBU skin permeation and distribution depending on their hydrolipophilic character could allow a rational design and an optimization of topical formulations.