Braz. J. Pharm. Sci. 2017;53(2):e15249 Page 1 / 12 Brazilian Journal of Pharmaceutical Sciences http://dx.doi.org/10.1590/s2175-97902017000215249 Article * Correspondence: E. Ricci-Júnior. Faculdade de Farmácia. Universidade Federal do Rio de Janeiro. Av. Carlos Chagas Filho, Ilha do Fundão - 21941-590 - Rio de Janeiro – RJ, Brazil. E-mail: ricci@pharma.ufrj.br Promotion of cutaneous penetration of nifedipine for nanoemulsion Paula de Oliveira Arantes 1 , Quesia Nery dos Santos 1 , Zaida Maria Faria de Freitas 1 , Alexandre dos Santos Pyrrho 2 , Cristal Cerqueira-Coutinho 3 , Ana Lucia Vazquez Villa 1 , Elisabete Pereira dos Santos 1 , Eduardo Ricci-Júnior 1,* 1 Faculty of Pharmacy, Galenic Development Laboratory (LADEG), Department of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 2 Faculty of Pharmacy, Laboratory for Immunoparasitology and Toxicological Analysis, Department of Clinical and Toxicological Analysis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 3 Technology Center, Institute of Macromolecules, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil This article reports the development and characterization of a nanoemulsion (NE) able to improve the cutaneous penetration of nifedipine. NE with nifedipine was development and characterized, presenting droplet size of 20 nm with low polydispersity index (IP<0.1), spherical shape without aggregation, pH compatible with typical skin levels and stability evaluated by seven months. In the permeation studies, a classical formulation based in an oil/water cream containing nifedipine was used for comparison with NE. Nanoemulsion promoted and improved the retention of nifedipine in the epidermis and dermis in relation to classical formulation. This promoting efect is related to the nanometric size of the droplets of the NE (20 nm), which give him a large superfcial area, favoring the contact of the nanocarrier with the skin surface. The NE was efcient in promoting accumulation of nifedipine in the dermis, which is the site of vasodilation action. NE was not irritating according to the primary dermal irritation tests. NE is a promising release system to promote cutaneous penetration of nifedipine and can be used in the future in clinical trials to promote healing of lesions caused by peripheral vascular diseases. Uniterms: Topical nifedipine/cutaneous permeation. Nanoemulsion/characterization. Stability. Cutaneous permeation/study. Healing of wounds. INTRODUCTION Topical nifedipine is used for various purposes, such as treatment of periocular and face wrinkles (Innocenti et al., 2010; Calabro et al., 2014), closure of anal fssures (Golfam et al. , 2010; Katsinelos et al. , 2006), and particularly to promote healing of skin wounds (Smith 2010; Melo et al., 2008; Ebadi et al., 2003). Nifedipine (NFD) is a calcium channel blocker and its use was frst recommended for treatment of cardiovascular diseases. Topical administration of nifedipine is advantageous to avoid the systemic effects of oral administration. For wound treatment, topical nifedipine has been employed to treat lesions caused by peripheral vascular disease and diabetes (Tosiello, Kopacki, 2000) as well as bedsores (Melo et al., 2008). Clinical studies have been published on the topical use of nifedipine to promote wound healing (Smith 2010; Tosiello, Kopacki, 2000). In the development of formulations for topical use, permeation studies are necessary to assess the drug’s safety and cutaneous retention. One of the main functions of the skin is to protect the organism from dehydration and harm from the environment. It is formed by the epidermis, dermis and hypodermis. The epidermis is the outer skin layer. The top part of the epidermis is the stratum corneum (SC), composed of unviable keratinized cells called corneocytes. These cells are surrounded by a lipid bilayer and joined by a complex lipid matrix. Therefore, the SC acts as a barrier that can control the permeation of drugs through the skin (Williams, 2003; Schaefer, Redelmeier, 1996). Drugs formulations for topical use must have high penetration in the SC, bioaccumulation in the viable epidermis and dermis and low or no systemic absorption, to avoid adverse side efects. The dermis is the action site of vasodilatory drugs as nifedipine. The great challenge of cutaneous