Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia.
J Control Release. 2018 Dec 28;292:13-17. doi: 10.1016/j.jconrel.2018.10.027. Epub 2018 Oct 23.
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.
牛奶以前被认为是一种潜在的基于脂质的药物传递系统，用于水溶性差的药物，但从未得到过广泛关注。部分原因是，依赖于基于脂质的制剂（在这种情况下是牛奶）中的溶解度并不能完全描述此类系统在消化过程中的行为。在此，我们使用时间分辨 X 射线散射证明，牛奶的消化实际上对水溶性差的药物卤泛群的溶解至关重要。选择卤泛群是因为它在基于脂质的制剂中的行为已经得到了广泛的研究，并且因为它与青蒿琥酯密切相关，青蒿琥酯是一种目前用于治疗小儿疟疾的抗疟药物。药物从牛奶悬浮液中的结晶固体形式转变为直接由于脂肪酶解而溶解的形式，这突出表明，考虑到牛奶脂质的消化是影响药物溶解和吸收的可用性的关键过程是至关重要的。
