Mechanochemistry of ibuprofen pharmaceutical Salvatore Andini a , Adele Bolognese a , Domenico Formisano a , Michele Manfra b , Fabio Montagnaro a , Luciano Santoro a,⇑ a Università di Napoli Federico II, Dipartimento di Scienze Chimiche, 80126 Napoli, Italy b Università della Basilicata, Dipartimento di Scienze dei Sistemi Colturali, Forestali e dell’Ambiente, 85100 Potenza, Italy article info Article history: Received 29 March 2011 Received in revised form 6 March 2012 Accepted 7 March 2012 Available online 1 April 2012 Keywords: Mechanochemistry Ibuprofen Expired pharmaceuticals Detoxification Decarboxilation abstract In this paper mechanochemistry has been studied in view of possible application to detoxification of expired pharmaceuticals. The experiments have been carried out with a commercial medication containing ibuprofen ((RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid) which has been submitted to prolonged milling up to 40 h. When Al(OH) 3 is used as co-reagent, the first degradation step induced by the mechan- ochemical treatment is an acid-base reaction with the ibuprofen carboxylic acid group. The subsequent degradation follows a complex pathway leading to 1-(4-isobutylphenyl)ethanone, 1-isobutyl-4-vinylbenzene and 2-(4-(3-methylbutan-2-yl)phenyl)propan-1-ol after 10 h milling and, in addition, 1-(4-acetylphenyl)-2- methylpropan-1-one, 1-(4-(1-hydroxy-2-methylpropyl)phenyl)ethanone and 1-(4-(2-hydroxy-2-methylpro- pyl)phenyl)ethanone after 40 h milling. The degradation reaction path and products have been identified by means of FT-IR spectroscopy, thin layer chromatography, NMR spectroscopy, mass spectroscopy and ele- mental analysis. The observed ibuprofen decarboxylation makes the drug simultaneously lose both its pharmaceutical activity and toxicity. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction In these last few years the disposal of expired pharmaceuticals has been acknowledged to constitute an issue of great concern by the environmentalists due to the environmental pollution by phar- maceutically active substances (PASs) that can negatively affect both the chemical and biochemical processes that take place in terrestrial and aquatic ecosystems. The persistence in the environ- ment of PASs such as erythromycin, cyclophosphamide, naproxen, sulfamethoxazole and sulfasalazine can last even more than a year (Halling-Sørensen et al., 1998; Di Guardo et al., 2008), while that of clofibric acid can overcome 21 years (Buser and Müller, 1998). In the cases of so long lifetimes the damage to the environment and health risk for humans can undoubtedly be severe. Furthermore, the presence of antibiotics in wastes can favor the growth of resis- tant bacteria strains with undesired pathogenic action. To this re- gard, the US National Library of Medicine and the National Institutes of Health have recently stated in their web site (http:// www.nlm.nih.gov/medlineplus/) that antibiotic resistance is still a major public health threat. In Italy, the disposal of expired pharmaceuticals is ruled by a specific act that makes compulsory the thermal degradation of PASs by incineration (DPR 15 Luglio 2003, n. 254). However, such processes are characterized by high investment and operation costs, because they require expensive and sophisticated equipment as well as total energy input to the process very much in excess to the fraction strictly necessary for the thermal degradation of PASs. The reason for this is that PASs are usually minor components of pharmaceutical formulations, the others being, in most cases, much less or not at all thermolabile. Then, less expensive processes based on safe and affordable procedures for the destruction of pharmaceuticals should be taken into consideration with increas- ing interest. One of the effective and nonpolluting techniques that have most recently gained attention for the treatment of wastes is mechano- chemistry (Guo et al., 2010). Particularly, it proved to be so suc- cessful for the treatment of asbestos containing materials that a patented process is now available able to convert toxic asbestos fi- bers into non-toxic amorphous form (Plescia et al., 2003). Other studies of environmental concern can be found in the pertinent lit- erature for the treatment of polycyclic aromatic hydrocarbons (Field et al., 1997) and organohalide compounds (Rowlands et al., 1994; Hall et al., 1996; Loiselle et al., 1996; Cao et al., 1999; Aresta et al., 2003; Tanaka et al., 2003, 2004; Birke et al., 2004; Zhang et al., 2010) as well as for the remediation of soils contaminated by heavy metals (Montinaro et al., 2007), the stabilization of lead in fly ashes (Nomura et al., 2010; Sun et al., 2011) and the detoxi- fication of model systems composed of alumina or silica contami- nated by hexadecane (Cioffi et al., 2008). The mechanisms responsible for the physical and chemical transformations that take place upon milling are of quite difficult 0045-6535/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.chemosphere.2012.03.025 ⇑ Corresponding author. Tel.: +39 081 674028; fax: +39 081 674090. E-mail address: santoro@unina.it (L. Santoro). Chemosphere 88 (2012) 548–553 Contents lists available at SciVerse ScienceDirect Chemosphere journal homepage: www.elsevier.com/locate/chemosphere