Transdermal patches and film forming solutions: the case of ammonio methacrylate

To assure a prolonged drug release to the skin, a pharmaceutical dosage form should firmly adhere to the skin over all the required treatment period. Taking into account this requirement, transdermal patches (TP) and film forming solutions (FFS) seem to be the most promising. TP has to be sticky and exhibit an optimal balance between shear and peel adhesion [1]. FFS should quickly dry on the skin and the formed film should be almost invisible, non-sticky with suitable mechanical properties [2]. Eudragit® RL (EuRL), opportunely plasticized, has been investigated for the preparation of both TP and FFS. Nevertheless, no information is available on rheological, adhesive and mechanical properties of plasticized EuRL. This work aimed to evaluate the effect of the addition of tributyl citrate or triacetin to EuRL on the characteristic reported above to identify the optimal ratios to design TP or FFS. To satisfy the requirements of flexibility necessary to assure a proper skin/dosage form contact, the material should have i) a glass transition temperature (Tg) below the skin surface temperature (~ 32 °C), ii) a viscoelastic pattern and iii) an elastic modulus lower than that of the skin. In the case of TP a certain degree of stickiness is required and it is generally recognized that this property is strictly related to a Tg lower than 40 °C with respect to the application temperature and to the rheological pattern. On the basis of these requirements, 10-30% and 40-60% w/w plasticizer appeared suitable to develop FFS and TP, respectively. As a proof, a series of placebo and drug loaded TP and FFS were prepared by using ibuprofen, ketoprofen or flurbiprofen and characterized. The drug loading decreased the relaxation time (R), as an indication of the increase of the matrix fluidity. The reduction of R had a beneficial effect on the drug release, but a detrimental influence on the adhesive properties, since the shear adhesion decreased. Therefore, to obtain TP with suitable adhesive properties and in vitro biopharmaceutical performances has been necessary to restrict the plasticizer range (40-50% w/w). Even in the case of FFS the range of plasticization was restricted with respect to the initial range. FFS designed with 20-30% w/w plasticizer presented negligible stickiness and Young modulus values lower than 3 MPa, which should assure an intimate and prolonged contact with the skin; furthermore, they were able to sustain the drug skin permeation, which resulted influenced also by the solvent evaporation. In conclusion, this work allowed to understand the influence of EuRL plasticization on the main TP and FFS features and to identify a formulative window to design both such dosage forms. References [1] Cilurzo F, Gennari CGM, Minghetti P. Adhesive properties: a critical issue in transdermal patch development. Expert Opin. Drug Deliv., 9, 1, 33-45, 2012. [2] Gennari, C.G.M., Selmin, F., Franzè, S., Musazzi, U.M., Quaroni, G.M.G., Casiraghi, A., Cilurzo, F. A glimpse in critical attributes to design autaneous film forming systems based on ammonium mehacrylate. J. Drug Deliv. Sci. Technol., 10.1016/j.jddst.2017.07.009, 2017.