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Lipid Compositions in Infant Formulas Affect the Solubilization of Antimalarial Drugs Artefenomel (OZ439) and Ferroquine during Digestion
journal contribution
posted on 2020-06-23, 19:05 authored by Malinda Salim, Gisela Ramirez, Kang-Yu Peng, Andrew J. Clulow, Adrian Hawley, Hanu Ramachandruni, Stephane Beilles, Ben J. BoydRecent
studies have shown that the solubilization of two antimalarial
drug candidates, artefenomel (OZ439) and ferroquine (FQ), designed
to provide a single-dose combination therapy for uncomplicated malaria
can be enhanced using milk as a lipid-based formulation. However,
milk as an excipient faces significant quality and regulatory hurdles.
We therefore have investigated infant formula as a potential alternative
formulation approach. The significance of the lipid species present
in a formula with different lipid compositions upon the solubilization
of OZ439 and FQ during digestion has been investigated. Synchrotron
small-angle X-ray scattering was used to measure the diffraction from
a dispersed drug during digestion and thereby determine the extent
of drug solubilization. High-performance liquid chromatography was
used to quantify the amount of drug partitioned into the digested
lipid phases. Our results show that both the lipid species and the
amount of lipids administered were key determinants for the solubilization
of OZ439, while the solubilization of FQ was independent of the lipid
composition. Infant formulas could therefore be designed and used
as milk substitutes to tailor the desired level of drug solubilization
while circumventing the variability of components in naturally derived
milk. The enhanced solubilization of OZ439 was achieved during the
digestion of medium-chain triacylglycerols (MCT), indicating the potential
applicability of MCT-fortified infant formula powder as a lipid-based
formulation for the oral delivery of OZ439 and FQ.