Encapsulation of Ibuprofen in CD-MOF and Related Bioavailability Studies

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.