Desenvolvimento, Formulação e Avaliação de Sistemas de Libertação Transdérmica Incorporando Sistemas Ternários de Complexação (Fármaco/Ciclodextrina/Polímero)

Abstract

Cyclodextrins are ciclic oligosaccharides with several pharmaceutical applications. They present a central hidrophobic cavity, whose structure allows the formation of stable inclusion complexes with many drugs. The aim of this work is to combine the cyclodextrin complex formation properties with their capacity of enhancing the permeation of drugs across the skin, using as a delivery system a transdermic matricial monolayer patch. Naproxen, a poorly soluble drug, is a good model for preparing cyclodextrin complexes. Binary complexes of Naproxen and hydrophilic ß-cyclodextrin, hidroxipropil-ß-cyclodextrin and methyl-ß-cyclodextrin were prepared. Ternary complexes combining the same cyclodextrins, Naproxen and the water soluble polymers hydroxypropylmethylcellulose and polyvinylpyrrolidone were also prepared. The application of several techniques such as solubility assays, nuclear magnetic resonance spectroscopy, differential scanning calorimetry, Fourier transformation infrared spectroscopy and X-ray diffractometry, allowed the detection and characterization of the inclusion complexes both in solution and in the solid state. The dissolution properties of Naproxen were used to select the best candidates to the preparation of controlled release formulations for transdermic application. Based on those results the choice relied on Naproxen complexed with ß-cyclodextrin or methyl-ß-cyclodextrin, with or without the water soluble polymers, prepared by the coevaporation method. Naproxen permeation studies, performed in pig skin, gave evidence that the permeation process is influenced by the polymeric matrix and that the kinetics is linear with the square root of time. The present study allowed to obtain a transdermic patch, containing a Naproxen methyl-ß-cyclodextrin-hydroxypropylmethylcellulose complex that appropriately promotes Naproxen permeation through the skin.