DESIGN OF LIGHT-STABLE FORMULATIONS OF NABUMETONE FOR TOPICAL USE: PHOTODEGRADATION STUDIES AND EX VIVO PERMEATION TESTS

Photosensitivity of many anti-inflammatory drugs is well known and several stability studies on this topic have been reported.1,3 Nabumetone, (4-(6-methoxy-2-naphthyl)-butan-2-one), is commercially available as tablets or suspension but is not formulated in cream or gel formulations because of its sensitivity to light. Photostability in water of the drug has been tested, describing the photoxidation of the side chain to 6-methoxy-2-naphthalene aldehyde as major product.4 In this study, the drug photodegradation was investigated in different matrices and niosomal formulations based on a series of surfactants were tested as photostabilization system (Figure 1). Photostability tests were performed on the drug in simple and niosomal gel, according to the ICH rules.5 The degradation process was monitored by spectrophotometric analysis and the data processed by Multivariate Curve Resolution (MCR), allowing to estimate spectra and concentration profiles of the components evolved. Characterization of the niosomes was made in terms of size and distribution by using Dynamic Light Scattering, the morphological analysis was carried out by Transmission Electron Microscopy and encapsulation efficiency by dialysis technique. Permeation experiments were made in non-occlusive conditions to better simulate the usual topical application of Nabumetone in gels for a period of 24 h. Photodegradation rate of the drug in simple gel showed a residual content of 90% after 24 min, under a stressing light exposure of 450 Wm-2. Photostability resulted increased significantly when the drug was entrapped in the niosomal system. The best results were obtained adopting niosomes in presence of Brij97 as surfactant. The niosomal gel demonstrated also to influence the permeation performance by enhancing the transdermal delivery of the drug through the skin. The proposed formulation could represent a valid opportunity to use Nabumetone to treat joint pain caused by osteoarthritis in the hands, wrists, elbows, knees, ankles, or feet. References 1. Zhang, N.; Liu, G., Liu; H., Wanga, Y., Hea, Z.; Wanga, G. J Hazard Mater 2011, 192, 411-418. 2. Hájková, R.; Solich, P.; Pospìšilová, M.; Šìcha, J. Anal Chim Acta 2002, 467, 91-96. 3. Ioele, G.; De Luca, M.; Tavano, L.; Ragno, G. Int J Pharm 2014, 465(1-2), 284-290. 4. Valero, M.; Costa, S.M.B. J Photochem Photobiol Chem 2003, 157, 93-101. 5. International Conference on Harmonization. ICH Q1A(R2), Stability testing of new drug substances and products, 2003, IFPMA, Geneva.