Research paper Physical characteristics and aerosol performance of naringin dry powders for pulmonary delivery prepared by spray-drying F. Sansone a , R.P. Aquino a , P. Del Gaudio a , P. Colombo b , P. Russo a, * a Department of Pharmaceutical Sciences, University of Salerno, Fisciano (SA), Italy b Department of Pharmacy, University of Parma, Parma, Italy article info Article history: Received 30 June 2008 Accepted in revised form 6 October 2008 Available online 1 November 2008 Keywords: Oxidative stress Naringin Dry powder inhaler Spray drying Excipient-free powders abstract The aim of the present work was to develop dry powders containing naringin for a direct administration to the lung to combat oxidative stress. Naringin microparticles were prepared by spray-drying the neat flavonoid (2–5% w/v) from different water/ethanol co-solvents. The spray-dried powders were character- ised for morphology, density, particle size distribution, residual humidity, crystallinity, solubility, ther- mal behaviour and respirable fraction. The fine fraction of the powders was measured by single-stage glass impinger and Andersen cascade impactor, using the Turbospin Ò device for the deposition tests, wherein the dose to be aerosolised was premetered in a gelatine capsule. By increasing the ethanol content, the feed liquid turned from a suspension into a solution: the spray of flavonoid suspensions led to powders with high crystallinity degree, low water solubility and high bulk density, while the spray of drug solutions led to more amorphous particles, with higher solubility, lower density and improved aerodynamic behaviour. The optimisation of the operative parameters produced enhanced aerosol performance of the flavonoid powders containing only the active compound. Ó 2008 Elsevier B.V. All rights reserved. 1. Introduction The lung, with its large surface and blood supply, is continually exposed to an environment rich in oxygen, and therefore suscepti- ble to injury mediated by oxidative stress. In order to prevent tis- sue damage, the airways of the lungs are endowed with several antioxidant defences, including glutathione, heme oxygenase, superoxide dismutase, vitamins C and E, beta-carotene, and uric acid [1]. However, when the presence of reactive oxygen or nitro- gen species (ROS and RNS, respectively), generated endogenously or exogenously, overcomes the physiologic antioxidant defences, an oxidative stress status occurs causing a number of lung disorders. Several previous reports have supported the theory of oxidative injury in asthma [2–5], chronic obstructive pulmonary disease (COPD) [6–9], and cystic fibrosis [10], and of a direct damage to epithelial cells [11] by ROS. Hydrogen peroxide and nitric oxide in the exhaled-breath condensates have been used as markers for oxidative processes affecting the lung [12–14]. Thus, the enhance- ment of the body antioxidant defences through the diet or through a pharmacological treatment can be a proper approach in airways diseases. Among the natural antioxidants, such as glutathione, vitamins, beta-carotene, and selenium, great attention has been fo- cused on flavonoids [15,16], polyphenolic compounds largely pres- ent in fruits and vegetables, having anti-inflammatory, antibacterial activities and well-documented antioxidant effect. As a drawback, flavonoids show a poor bioavailability due to their susceptibility to oxidation, degradation in the gastric pH, very slight solubility in water and very low dissolution rate, leading to an irregular absorption from oral solid dosage forms [17]. Although a number of publications have been focused on the antioxidant ef- fect of flavonoids, almost no attention has been addressed to their formulation in order to improve the bioavailability. Recently, oral hydrophilic swellable matrices [18,19] and gastroresistant micro- particles have been formulated [20,21]. An alternative strategy may be to achieve higher local concentration of the antioxidant in the respiratory tissue by delivering the aerosol directly to the airways of the lung by a nebulizer, a pressurised metered dose in- haler (pMDI) or a dry powder inhaler (DPI). Compared to nebulis- ers, DPIs are handy, easy to use and less expensive; moreover, contrarily to pMDI, they are propellant-free and do not require coordination between the device actuation and the patient inspira- tion. Finally, the dry powder formulation can improve the drug physicochemical and microbiological stability [22], and can assure a higher drug concentration at the deposition site. Thus, the aim of 0939-6411/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2008.10.007 * Corresponding author. Department of Pharmaceutical Sciences, University of Salerno, via Ponte don Melillo, 84084 Fisciano (SA), Italy. Tel.: +39 089969256; fax: +39 089969602. E-mail address: paorusso@unisa.it (P. Russo). European Journal of Pharmaceutics and Biopharmaceutics 72 (2009) 206–213 Contents lists available at ScienceDirect European Journal of Pharmaceutics and Biopharmaceutics journal homepage: www.elsevier.com/locate/ejpb