The rule of five for non-oral routes of drug delivery: Ophthalmic, inhalation and transdermal

Young Bin Choy, Mark R. Prausnitz

Research output: Contribution to journalReview article

66 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)943-948
Number of pages6
JournalPharmaceutical Research
Volume28
Issue number5
DOIs
StatePublished - 1 May 2011

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Drug delivery
Inhalation
Pharmaceutical Preparations
Skin
Macromolecules
Permeability
Technology

Keywords

  • Lipinski's Rule of Five
  • absorption
  • drug design
  • drug-like properties
  • inhalation
  • ophthalmic
  • physicochemical properties
  • predictive drug delivery
  • pulmonary
  • tissue permeability
  • transdermal

Cite this

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The rule of five for non-oral routes of drug delivery : Ophthalmic, inhalation and transdermal. / Choy, Young Bin; Prausnitz, Mark R.

In: Pharmaceutical Research, Vol. 28, No. 5, 01.05.2011, p. 943-948.

Research output: Contribution to journalReview article

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