The impact of digestion is essential to the understanding of milk as a drug delivery system for poorly water soluble drugs

[摘要] Milk has previously been considered as a potential lipid-based drug delivery system for poorly water soluble drugs but it has never gained significant attention. This is in part because relying on solubility in lipid-based formulations (in this case milk) does not provide a complete picture of the behavior of such systems upon digestion. Herein, we demonstrate using time resolved X-ray scattering that the digestion of milk is actually crucial to the solubilisation of a poorly water-soluble drug, halofantrine. Halofantrine was chosen because its behaviour in lipid-based formulations has been widely investigated and because of its close structural relationship to lumefantrine, an antimalarial drug of current interest for the treatment of paediatric malaria. The transformation of the drug from a crystalline solid form in suspension in milk, to a solubilised form as a direct consequence of lipolysis highlights that consideration of digestion of the milk lipids as a critical process that influences drug solubilisation and availability for absorption is vital.

[发布日期] 2018-12-28

[关键词] Milk;Lipid-based formulation;Drug solubilisation;Polymorphism;X-ray scattering;In vitro digestion;Halofantrine;Weakly basic drug