Projects per year
Delamanid is a poorly water-soluble drug currently being used for the treatment of tuberculosis. The high frequency of dosing leads to poor adherence for patients who live in lower economic and nomadic populations. Non-digestible self-assembling lipids as a formulation approach for poorly water-soluble drugs have previously been shown to extend the window of absorption through gastric retention. We hypothesise that this approach could lead to the reduction of dosing frequency for delamanid and thereby has potential to improve adherence. Formulations of delamanid were prepared in selachyl alcohol and phytantriol as non-digestible self-assembling lipid vehicles, and their behaviour was compared with reconstituted milk powder, as a digestible lipid-based formulation, and an aqueous suspension. The self-assembly of selachyl alcohol and phytantriol in aqueous media in the presence of delamanid was studied using small angle X-ray scattering and produced the inverse hexagonal (H2) and inverse bicontinuous cubic (V2) liquid crystal structures, respectively. The times at which maximum delamanid levels in plasma were observed (Tmax) after oral administration of the phytantriol, selachyl alcohol and reconstituted milk powder formulations of delamanid to rats were 27 ± 3, 20 ± 4 and 6.5 ± 1.0 h, respectively, compared with the aqueous suspension formulation with a Tmax of 3.4 ± 1 h, which confirms the hypothesis of an extended duration of absorption after administration in non-digestible self-assembling lipids. The digestion products of the triglycerides in the milk formulation increased the solubilisation of delamanid in the gastrointestinal tract, leading to an increase in exposure compared with the aqueous suspension formulation but did not significantly extend Tmax. Overall, the non-digestible nanostructured lipid formulations extended the duration of absorption of delamanid well beyond that from milk or suspension formulations.
|Number of pages||9|
|Journal||Drug Delivery and Translational Research|
|Publication status||Published - Jun 2021|
- Lipid formulation
- Lyotropic liquid crystal
- Small angle X-ray scattering
- Sustained release
- 1 Finished
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
Davis, T., Boyd, B., Bunnett, N., Porter, C., Caruso, F., Kent, S., Thordarson, P., Kearnes, M., Gooding, J., Kavallaris, M., Thurecht, K., Whittaker, A. K., Parton, R., Corrie, S. R., Johnston, A., McGhee, J., Greguric, I. D., Stevens, M. M., Lewis, J., Lee, D. S., Alexander, C., Dawson, K., Hawker, C., Haddleton, D., Thierry, B., Prestidge, C. A., Meyer, A., Jones-Jayasinghe, N., Voelcker, N. H., Nann, T. & McLean, K.
Australian Research Council (ARC), Monash University, University of Melbourne, University of New South Wales (UNSW), University of Queensland , University of South Australia, Monash University – Internal Faculty Contribution, University of Wisconsin Madison, Memorial Sloan Kettering Cancer Center, University of California System, University College Dublin, Imperial College London, University of Warwick, SungKyunKwan University, Australian Nuclear Science and Technology Organisation (ANSTO) , University of Nottingham
30/06/14 → 29/06/21