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Nanostructured reverse hexagonal liquid crystals sustain plasma concentrations for a poorly water-soluble drug after oral administration

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Abstract

Reverse hexagonal (H2) liquid crystals formed from selachyl alcohol were demonstrated to sustain the absorption of the poorly water-soluble drug cinnarizine (CZ) after oral administration to rats. When CZ was administered as a bolus lipid solution in selachyl alcohol, the T max was observed to be 23.5 ± 5.9 h, significantly longer than the control suspension (1 h). Administration of selachyl alcohol as dispersed nanoparticles (hexosomes) also resulted in a sustained plasma profile, with drug concentrations maintained from 20 to 40 ng/mL over the first 24 h after administration. Sustained absorption of CZ from the selachyl alcohol hexosomes led to a significant enhancement (p < 0.05) in oral bioavailability (F% = 17%) compared to the control CZ suspension (9%). Analysis of selachyl alcohol hexosomes using small-angle x-ray scattering indicated that neither the presence of CZ (7 mg/g) nor simulated intestinal fluid altered the H2 nanostructure. Selachyl alcohol is not susceptible to digestion. Prolonged absorption from the selachyl alcohol-based H2 systems was attributed to the non-digestible nature of the lipid, similar to non-digestible phytantriol cubic (V2) systems previously reported. Furthermore, the likely presence of non-sink conditions in the gastric compartment provides a drug reservoir requiring gastric emptying to stimulate drug release from the formulation. This study highlights the potential use of non-digestible liquid crystalline systems generally and nanostructured liquid crystalline particles in particular as novel sustained oral drug delivery systems.

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Acknowledgements

The authors thank Nikko Chemicals for the kind donation of selachyl alcohol to these studies. The authors also thank the Australian Institute of Nuclear Science and Engineering for funding of the SAXS studies (grant AINGRA06018). This research was undertaken on the small- and wide-angle scattering beamline at the Australian Synchrotron, VIC, Australia. T-H N. thanks Monash Research Graduate School for financial support.

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  1. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, VIC, Australia

    Tri-Hung Nguyen, Christopher J. H. Porter & Ben J. Boyd

  2. Bragg Institute, Australian Nuclear Science and Technology Organisation, Menai, NSW, Australia

    Tracey Hanley

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  1. Tri-Hung Nguyen
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  2. Tracey Hanley
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Correspondence to Ben J. Boyd.

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Nguyen, TH., Hanley, T., Porter, C.J.H. et al. Nanostructured reverse hexagonal liquid crystals sustain plasma concentrations for a poorly water-soluble drug after oral administration. Drug Deliv. and Transl. Res. 1, 429–438 (2011). https://doi.org/10.1007/s13346-011-0045-z

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