Desenvolvimento de formulações para aplicação tópica contendo Benzofenonas: estudos in vitro e in vivo

Abstract

This study aimed to develop a formulation for topical administration of a new compound with anti-inflammatory activity, a benzophenone called LFQM117. Topical administration has many advantages over systemic therapy, especially in treatments of specific diseases of the skin and for drugs which have systemic side effects and low bioavailability. However, a major challenge in developing topical products is to overcome the skin barrier and further control the release and the amount of drug that reaches the different skin layers. Physicochemical characteristics of the drug and the delivery system are responsible for this differential drug distribution in various skin layers. Thus, the present work, besides perform a physicochemical study to characterize the new molecule, LFQM117, evaluated if developed formulations were able to provide adequate skin penetration of the drug. Liquid crystalline systems have interesting features for topical administration such as lipid layer structure and gel form, ability to incorporate hydrophilic, lipophilic and amphiphilic molecules, modulate the release of these substances and the possibility to incorporate cutaneous absorption promoters in the formulation. Therefore these systems were investigated as vehicles for LFQM117’s topical formulation. The results of this study demonstrated that LFQM117 is a stable molecule, but water-insoluble, highly nonpolar (log P = 4.8) and low skin permeability. Lamellar liquid crystalline phases consisting of monoolein: oleic acid: propylene glycol: water was able to increase the amount of LFQM117 retained in the epidermis without favoring a permeation skin, which is suitable for topical products. For these type of products it is expected a maximum retention skin with minimal skin permeation. Finally, topical anti- inflammatory action in vivo of LFQM117 formulations was evaluated as the inhibition of the croton oil-induced ear edema, as well as myeloperoxidase activity assay, demonstrating that lamellar mesophases composed of monoolein are promising systems for the administration of benzophenone LFQM117, as a topical anti- inflammatory.