International Journal of Pharmaceutics 458 (2013) 39–47 Contents lists available at ScienceDirect International Journal of Pharmaceutics j o ur nal ho me page: www.elsevier.com/locate/ijpharm Personalised Medicine Further experimentation of inhaled; Lantus, Actrapid and Humulin with todays’ production systems Paul Zarogoulidis a,b,∗ , Dimitris Petridis c , Christos Ritzoulis c , Qiang Li d , Haidong Huang d , Yunye Ning d , Kaid Darwiche b , Lutz Freitag b , Konstantinos Zarogoulidis a a Pulmonary Department, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece b Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany c Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, Thessaloniki, Greece d Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, China a r t i c l e i n f o Article history: Received 10 September 2013 Received in revised form 30 September 2013 Accepted 2 October 2013 Available online 17 October 2013 Keywords: Aerosol insulin Jet-nebulizers Ultrasound Chemical compounds studied in this article: Lantus (PubChem CID: 44146714) Actrapid (PubChem SID: 135350514) Humulin Regular (PubMed CID: 16129672) Cisplatin (PubChem CID: 84093) Carboplatin (PubChem CID: 10339178) Paclitaxel (PubChem CID: 36314) Docetaxel (PubChem CID: 148124) Gemcitabine (PubChem CID: 60750) Doxorubicin (PubChem CID: 31703) Tobramycin (PubChem CID: 36294) a b s t r a c t Background: Several aerosol production systems have been used for aerosol insulin production. How- ever; since the first studies several new models of jet-nebulizers and ultrasound nebulizers have been introduced in the market. Materials and methods: Three different models of jet-nebulizers (different brands, same properties) and three different ultrasound nebulizers (different brands, same properties). Six residual cups (2 small ≤ 6 ml and 3 large ≤ 8 ml) were used for the jet-nebulizers. The ultrasound nebulizers were used with their facemasks or with their inlets which were included in the purchase package. Results: Ultrasound nebulizers; LANTUS produces by far the lowest mean droplets (2.44) half the size of the other two drugs (4.43 = 4.97). GIMA nebulizer is the most efficient producing one third of the droplet size of SHIMED and one second of EASYNEB (2.06 < 3.15 < 6.62). Finally, the 4 ml loading concentration is more suitable for supporting the production of smaller droplets (3.65 < 4.24). Drugs and nebulizers act interactively yielding very large droplets when ACTRAPID and HUMULIN are administered in joint with SHIMED nebulizer (9.59 = 7.72). Jet-nebulizers; HUMULIN again is the least preferred insulin since it hardly reaches the low but equal performance of others at the loading level of 6 ml. Residual cups E and B produce uniquely lower mean droplets at loading level 6. Conclusions: Ultrasound nebulizers; the best suggested combination should be LANTUS insulin, GIMA nebulizer administered at loading dose of 4 ml jet-nebulizers. A global review can give the best com- bination: the lowest mean droplets are produced when the drugs LANTUS (mostly) and ACTRAPID are administered, applying the SUNMIST nebulizer in concert with residual cup B at loading levels of 6 ml. © 2013 Elsevier B.V. All rights reserved. 1. Introduction In an effort to deliver efficient drug concentration in the tar- get site and reduce the side effects several intravenous therapies are being investigated with alternative methods of administra- tion. Inhaled insulin is such an example where a product was redesigned to be administered as aerosol (Zarogoulidis et al., 2011). Several other therapies are also investigated whether they could be delivered with safety as aerosols and with efficiency (Darwiche ∗ Corresponding author at: Pulmonary Department, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. Tel.: +30 2310992433; fax: +30 2310992432. E-mail addresses: pzarog@hotmail.com, ppneumon@yahoo.com (P. Zarogoulidis). et al., 2013; Zarogoulidis et al., 2012a, 2012b). The main advan- tages of the respiratory system are the ability to absorb rapidly from a large area (100 m 2 alveoli) the inhaled drug and trans- port it to the systemic blood circulation and lymphatic circulation (Shinohara, 1997; Swift, 1980). However; the respiratory tract has several defense mechanisms which can be summarized; (a) beating cilia, (b) regional macrophages, (c) mucus, (d) local gene expression and (e) local transporters (Bosquillon, 2010). Addition- ally, there are several respiratory diseases that modify the several aspects of the aerosol deposition and absorption. Underlying respi- ratory diseases and their exacerbations, such as; (a) asthma, (b) chronic obstructive pulmonary disease (COPD), (c) cystic fibrosis change and (d) respiratory infection modify the airway diameter and increase mucus production. Therefore therapeutic pre-aerosol treatment has been proposed either with inhaled bronchodila- tors or inhaled cortisone (Becker et al., 2006; Himmelmann et al., 0378-5173/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijpharm.2013.10.019