Encapsulation of Ibuprofen in CD-MOF and Related Bioavailability Studies

Karel J. Hartlieb, Daniel P. Ferris, James M. Holcroft, Irawati Kandela, Charlotte L. Stern, Majed S. Nassar, Youssry Y. Botros, J. Fraser Stoddart*

*Corresponding author for this work

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Although ibuprofen is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs), it exhibits poor solubility in aqueous and physiological environments as a free acid. In order to improve its oral bioavailability and rate of uptake, extensive research into the development of new formulations of ibuprofen has been undertaken, including the use of excipients as well as ibuprofen salts, such as ibuprofen lysinate and ibuprofen, sodium salt. The ultimate goals of these studies are to reduce the time required for maximum uptake of ibuprofen, as this period of time is directly proportional to the rate of onset of analgesic/anti-inflammatory effects, and to increase the half-life of the drug within the body; that is, the duration of action of the effects of the drug. Herein, we present a pharmaceutical cocrystal of ibuprofen and the biocompatible metal-organic framework called CD-MOF. This metal-organic framework (MOF) is based upon γ-cyclodextrin (γ-CD) tori that are coordinated to alkali metal cations (e.g., K+ ions) on both their primary and secondary faces in an alternating manner to form a porous framework built up from (γ-CD)6 cubes. We show that ibuprofen can be incorporated within CD-MOF-1 either by (i) a crystallization process using the potassium salt of ibuprofen as the alkali cation source for production of the MOF or by (ii) absorption and deprotonation of the free-acid, leading to an uptake of 23-26 wt % of ibuprofen within the CD-MOF. In vitro viability studies revealed that the CD-MOF is inherently not affecting the viability of the cells with no IC50 value determined up to a concentration of 100 μM. Bioavailability investigations were conducted on mice, and the ibuprofen/CD-MOF pharmaceutical cocrystal was compared to control samples of the potassium salt of ibuprofen in the presence and absence of γ-CD. From these animal studies, we observed that the ibuprofen/CD-MOF-1 cocrystal exhibits the same rapid uptake of ibuprofen as the ibuprofen potassium salt control sample with a peak plasma concentration observed within 20 min, and the cocrystal has the added benefit of a 100% longer half-life in blood plasma samples and is intrinsically less hygroscopic than the pure salt form.

Original languageEnglish (US)
Pages (from-to)1831-1839
Number of pages9
JournalMolecular Pharmaceutics
Volume14
Issue number5
DOIs
StatePublished - May 1 2017

Keywords

  • cyclodextrin
  • drug delivery
  • ibuprofen
  • metal−organic framework

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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    Hartlieb, K. J., Ferris, D. P., Holcroft, J. M., Kandela, I., Stern, C. L., Nassar, M. S., Botros, Y. Y., & Stoddart, J. F. (2017). Encapsulation of Ibuprofen in CD-MOF and Related Bioavailability Studies. Molecular Pharmaceutics, 14(5), 1831-1839. https://doi.org/10.1021/acs.molpharmaceut.7b00168