PHOTOSTABILITY AND EX-VIVO PERMEATION STUDIES ON DICLOFENAC IN TOPICAL NIOSOMAL FORMULATION

Photosensitivity of Diclofenac (DC) is well known and several stability studies have been reported, describing also the formation of several impurities as 1-(2,6-dichlorophenyl)indolin-2-one and other quinone derivatives [1-3]. In a previous study, we have defined the photodegradation profile of DC in solution and semi-solid commercial specialties and proposed photostabilization systems through addition of chemical UV-absorbers or by incorporating the drug into cyclodextrin matrices.[4] In this study, novel niosomal gels were designed as photostabilization systems. Moreover, ascorbic acid was added, because its antioxidant property. Photodegradation experiments were made by applying photostability tests to commercial formulations containing the drug and to novel prepared gels, according to the ICH rules.[5] The degradation process was monitored by spectrophotometric analysis and the data were processed by Multivariate Curve Resolution (MCR) technique to estimate spectra and concentration profiles of the components evolved. Characterization of niosomes was evaluated in terms of size and distribution, carried out by Dynamic Light Scattering, morphological analysis by Transmission Electron Microscopy and encapsulation efficiency using the dialysis technique. Permeation experiments were made in non-occlusive conditions to better simulate the usual topical application of DC in gels for a period of 24 h. Photodegradation rate of DC in gel was found very fast, with a residual content of 90% after only 3.90 min, under a radiant exposure of 450 Wm-2. Photostability of the drug resulted increased significantly in comparison with that of the commercial formulations when the drug was entrapped in the niosomal systems. The best results were obtained by incorporating the drug in niosomes in presence of ascorbic acid, resulting in a degradation of 10% after 50.01 min of light exposure. The niosomal gel demonstrated to increase significantly the photostability of DC and influence its permeation capability by enhancing the transdermal delivery of the drug that easily penetrated through the skin respect to conventional pharmaceutical formulations. References [1] Zhang, N.; Liu, G., Liu; H., Wanga, Y., Hea, Z.; Wanga, G. Diclofenac photodegradation under simulated sunlight: Effect of different forms of nitrogen and Kinetics. J Hazard Mater 2011, 192, 411-418. [2] Hájková, R.; Solich, P.; Pospìšilová, M.; Šìcha, J. Simultaneous determination of methylparaben, propylparaben, sodium diclofenac and its degradation product in a topical emulgel by reversed-phase liquid chromatography. Anal Chim Acta 2002, 467, 91-96. [3] Salgado, R.; Pereira, V.J.; Carvalho, G.; Soeiro, R.; Gaffney, V.; Almeida, C.;, Vale Cardoso, V.; Ferreira, E.; Benoliel, M.J.; Ternes, T.A.; Oehmena, A.; Reis, M.A.M.; Noronha, J.P. Photodegradation kinetics and transformation products of ketoprofen, diclofenac and atenolol in pure water and treated wastewater. J Hazard Mater 2013, 244-245, 516-527. [4] Ioele, G.; De Luca, M.; Tavano, L.; Ragno, G. The difficulties for a photolabile drug in topical formulations: The case of diclofenac. Int J Pharmac 2014, 465(1-2), 284-290. [5] International Conference on Harmonization. ICH Q1A(R2), Stability testing of new drug substances and products, 2003, IFPMA, Geneva.