Design and Evaluation of a New Transdermal Formulation Containing Estradiol Paola Maffeia, Annalisa Sforzinia, Simone Lombardi Borgiaa, Celestino Ronchib, Norberto Festoc, and Gian Carlo Ceschela
Dipartimento di Scienze Farmaceutiche, Facolta ` di Farmacia, Universita ` degli Studi di Bolognaa, Bologna (Italy), Montefarmaco Research s.r.l.b, Pero, Milano (Italy), and Inpharma SAc, Lugano (Switzerland)
Estradiol is an important pharmacologically active drug with good skin permeation. It does not induce side effects like an overproduction of unwanted hepatic proteins. In this study the feasibility of a new formulation for the local delivery of estradiol consisting of an anhydrous gel, with a high percentage of ethanol, forming an invisible and non-irritating film on the skin was tested. The formulation was designed in order to delay the liberation of estradiol and to slow down the skin estradiol permeation with a consequent prolonged drug action that would reduce the number of applications. For this reason, two different gel-forming polymers were added to the basic formulation: KlucelÒHF (hydroxypropyl cellulose) and Polymer-LenÒ, a polymer made by copolymerization of lauryl methacrylate with N-vinyl pyrrolidone. From in vitro permeation studies it was pointed out that hydroxypropyl cellulose and the copolymer act on drug permeation in two opposite ways with respect to the basic formulation. In fact, the copoly-mer decreases drug permeation while hydroxypropyl cellulose increases it.
Therefore, the copolymer of lauryl methacrylate with N-vinyl pyrrolidone is well suited to delay permeation and to achieve the desired formulation properties.
Key words Estradiol • Hydroxypropyl cellulose • Lauryl methacrylate • Skin permeation, sustained • Transdermal drug formulations • N-Vinyl pyrrolidone
