Mechanism of Hydrogen-Bonded Complex Formation between Ibuprofen and Nanocrystalline Hydroxyapatite

Abstract

Nanocrystalline hydroxyapatite (nanoHA) is the main hard component of bone and has the potential to be used to promote osseointegration of implants and to treat bone defects. Here, using active pharmaceutical ingredients (APIs) such as ibuprofen, we report on the prospects of combining nanoHA with biologically active compounds to improve the clinical performance of these treatments. In this study, we designed and investigated the possibility of API attachment to the surface of nanoHA crystals via the formation of a hydrogen-bonded complex. The mechanistic studies of an ibuprofen/nanoHA complex formation have been performed using a holistic approach encompassing spectroscopic (Fourier transform infrared (FTIR) and Raman) and X-ray diffraction techniques, as well as quantum chemistry calculations, while comparing the behavior of the ibuprofen/nanoHA complex with that of a physical mixture of the two components. Whereas ibuprofen exists in dimeric form both in solid and liquid state, our study showed that the formation of the ibuprofen/nanoHA complex most likely occurs via the dissociation of the ibuprofen dimer into monomeric species promoted by ethanol, with subsequent attachment of a monomer to the HA surface. An adsorption mode for this process is proposed; this includes hydrogen bonding of the hydroxyl group of ibuprofen to the hydroxyl group of the apatite, together with the interaction of the ibuprofen carbonyl group to an HA Ca center. Overall, this mechanistic study provides new insights into the molecular interactions between APIs and the surfaces of bioactive inorganic solids and sheds light on the relationship between the noncovalent bonding and drug release properties.

Bioactive Hydrogel Marbles

“…This observation could be explained by the interaction between IBU and H-BGNPs. Works have stated that the IBU might form hydrogen-bonded complexes with the silanol groups on silica surfaces and with the growing hydroxyapatite layer on the BHM shell 54 , 55 . BSA had a slower release profile than IBU (P < 0.001) with a complete release around 60% that appeared to be governed by diffusion and swelling (Fig.…”

Bisphosphonate-Functionalized Hydroxyapatite Nanoparticles for the Delivery of the Bromodomain Inhibitor JQ1 in the Treatment of Osteosarcoma

“…Also, hydrolysis of the tert -butyl ester, forming negatively charged carboxylate group free to bind to Ca 2+ ions of HAp, would require more reactive solvents, while the single nitrogen with a lone pair involved in the π system is less alkaline than its three sp 2 counterparts and thus less prone to protonation, given that the latter would have a more disruptive effect on the aromaticity of the ring. Although theoretical, density functional studies delineated hydrogen-bonded interactions, involving the OH − group of HAp, as dominant in binding ibuprofen to HAp, 33 they ignored the diffusivity and the intense exchange of this group across the solid/solution interface. Despite the electrostatic interaction with HAp, the main effect of the physisorption of JQ1 is exhibited through increasing the hydrophobicity of the surface and thus affecting the growth habit of individual particles.…”

On-line analysis and in situ pH monitoring of mixed acid fermentation by Escherichia coli using combined FTIR and Raman techniques

“…After wavenumber calibration, Raman peak position accuracy is estimated to be ± 3 cm −1 (for more details, see refs. [32][33][34][35] and the Electronic Supplementary Material (ESM)). Raman spectra were recorded every 5 min in 10 accumulations of 30 s.…”