Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
SAXS/WAXS Beamline, Australian Synchrotron, ANSTO, 800 Blackburn Road, Clayton, Victoria 3169, Australia.
Int J Pharm. 2019 Jan 10;554:179-189. doi: 10.1016/j.ijpharm.2018.10.069. Epub 2018 Oct 31.
Oral delivery of dispersible tablets is a preferred route of administration for paediatrics due to ease of administration and dose control. Milk has gained interest as a drug delivery system due to its ability to dissolve poorly water-soluble drugs. There are no reports of milk tablet formulations being assessed in the context of lipid digestion, which is critical in influencing orally administered drug solubility and bioavailability. Milk-drug tablets were formulated by blending freeze-dried bovine milk or infant formula with the poorly water-soluble drug cinnarizine, which were directly compressed. Tablet strength, friability and dispersibility were quantified and synchrotron X-ray scattering was used to determine the lipid liquid crystalline phases formed during in vitro digestion of dispersed tablets and their effects on drug solubilisation. Tableting had a significant impact on the self-assembly of lipids in redispersed milk tablets whereas no effect was seen for infant formula tablets. Incorporation of the disintegrant poly(vinylpolypyrrolidone) to reduce tablet dispersion times promoted the formation of hexagonal liquid crystalline phases upon digestion but had minimal effect on drug solubilisation. These findings show that similar to the use of liquid milk, the formulation of milk-drug tablets can be used to improve solubilisation of poorly water-soluble drugs.
口服分散片是儿科首选的给药途径,因为其给药方便且易于控制剂量。由于其能够溶解水溶性差的药物,因此牛奶已成为药物传递系统的研究热点。目前尚无关于在脂质消化背景下评估牛奶片剂制剂的报道,而脂质消化对于影响口服药物的溶解度和生物利用度至关重要。通过将冻干牛奶奶粉或婴儿配方奶粉与水溶性差的药物肉桂嗪混合,然后直接压缩,制备牛奶-药物片剂。对片剂的强度、脆性和分散性进行了定量分析,并利用同步加速器 X 射线散射技术来确定分散片剂体外消化过程中形成的脂质液晶相及其对药物溶解的影响。压片对再分散牛奶片剂中脂质的自组装有显著影响,而对婴儿配方奶粉片剂则没有影响。加入崩解剂聚乙烯基吡咯烷酮以减少片剂分散时间,有利于在消化过程中形成六方液晶相,但对药物溶解的影响很小。这些发现表明,类似于使用液态奶,牛奶-药物片剂的配方可用于改善水溶性差的药物的溶解。