caa a22 4500 445313757 CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11095-010-0292-6 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0292-6 The Rule of Five for Non-Oral Routes of Drug Delivery: Ophthalmic, Inhalation and Transdermal [Elektronische Daten] [Young Choy, Mark Prausnitz] ABSTRACT: The Rule of Five predicts suitability of drug candidates, but was developed primarily using orally administered drugs. Here, we test whether the Rule of Five predicts drugs for delivery via non-oral routes, specifically ophthalmic, inhalation and transdermal. We assessed 111 drugs approved by FDA for those routes of administration and found that >98% of current non-oral drugs have physicochemical properties within the limits of the Rule of Five. However, given the inherent bias in the dataset, this analysis was not able to assess whether drugs with properties outside those limits are poor candidates. Indeed, further analysis indicates that drugs well outside the Rule of Five limits, including hydrophilic macromolecules, can be delivered by inhalation. In contrast, drugs currently administered across skin fall within more stringent limits than predicted by the Rule of Five, but new transdermal delivery technologies may make these constraints obsolete by dramatically increasing skin permeability. The Rule of Five does appear to apply well to ophthalmic delivery. We conclude that although current non-oral drugs mostly have physicochemical properties within the Rule of Five thresholds, the Rule of Five should not be used to predict non-oral drug candidates, especially for inhalation and transdermal routes. Springer Science+Business Media, LLC, 2010 absorption nationallicence drug design nationallicence drug-like properties nationallicence inhalation nationallicence Lipinski's Rule of Five nationallicence ophthalmic nationallicence physicochemical properties nationallicence predictive drug delivery nationallicence pulmonary nationallicence tissue permeability nationallicence transdermal nationallicence Choy Young Department of Biomedical Engineering College of Medicine and Institute of Medical & Biological Engineering Medical Research Center, Seoul National University, 110-799, Seoul, Republic of Korea aut Prausnitz Mark School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 30332-0100, Atlanta, Georgia, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 943-948 0724-8741 28:5<943 2011 28 11095 https://doi.org/10.1007/s11095-010-0292-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0292-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Choy Young Department of Biomedical Engineering College of Medicine and Institute of Medical & Biological Engineering Medical Research Center, Seoul National University, 110-799, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Prausnitz Mark School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 30332-0100, Atlanta, Georgia, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 943-948 0724-8741 28:5<943 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer