Biocompatible lidocaine and prilocaine loaded-nanoemulsion system for enhanced percutaneous absorption: QbD-based optimisation, dermatokinetics and in vivoevaluation

Nanoemulsions consist in very fine oil-in-water dispersions, having droplet diameter smaller than 100 nm. Compared to microemulsions, they are in a metastable state, and their structure depends on the history of the system. In the present work, nanoemulsions were prepared with a high shear device, which is less constraining than spontaneous emulsification procedures. Nanoemulsions are very fragile systems by nature. As they are transparent, the slightest sign of destabilisation appears visually. Two major sources of unstability were identified and extensively studied: Ostwald ripening and depletion induced floculation following the addition of thickening polymers. The control of these two mechanisms allowed the industrial production of a large variety of cosmetic products, from water-like fluids, to ringing gels obtained by increasing the oil phase content or by adding polymers. The nanoemulsions are easily valued in skin care due to their good sensorial properties (rapid penetration, merging textures) and their biophysical properties (especially their hydrating power).

It is preferred that topically administered drugs act either dermally or transdermally. For that reason they have to penetrate into the deeper skin layers or permeate the skin. The outermost layer of the human skin, the stratum corneum, is responsible for its barrier function. Most topically administered drugs do not have the ability to penetrate the stratum corneum. In these cases modulations of the skin penetration profiles of these drugs and skin barrier manipulations are necessary. A skin penetration enhancement can be achieved either chemically, physically or by use of appropriate formulations. Numerous chemical compounds have been evaluated for penetration-enhancing activity, and different modes of action have been identified for skin penetration enhancement. In addition to chemical methods, skin penetration of drugs can be improved by physical options such as iontophoresis and phonophoresis, as well as by combinations of both chemical and physical methods or by combinations of several physical methods. There are cases where skin penetration of the drug used in the formulation is not the aim of the topical administration. Penetration reducers can be used to prevent chemicals entering the systemic circulation. This article concentrates on the progress made mainly over the last decade by use of chemical penetration enhancers. The different action modes of these substances are explained, including the basic principles of the physical skin penetration enhancement techniques and examples for their application.