Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine
Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine
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DOI：
10.1016/s0378-5173(98)00054-4
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发表时间：
1998-06-01
影响因子：
5.8
通讯作者：
Charman, WN
中科院分区：
文献类型：
--
作者：
Khoo, SM;Humberstone, AJ;Charman, WN
在禁食的比格犬中研究了自乳化给药系统（SEDDS）和自微乳化给药系统（SMEDDS）改善吸收不良的抗疟药（Halofantrine，Hf）口服生物利用度的潜力。研究了Hf游离碱，而不是市售盐酸盐（Hf.HCl），因为其在甘油三酯溶剂中的溶解度高得多。多组分递送系统通过评估它们在温和搅拌下引入水性介质时的自分散能力以及通过测定所得乳液的粒度来优化。选择用于生物利用度评估的优化制剂为中链甘油三酯SEDDS和SMEDDS以及长链甘油三酯SMEDDS。Hf及其脱丁基代谢产物的相关药代动力学参数相对于静脉内制剂进行测定。相对于固体Hf.HCl片剂制剂的先前数据，Hf碱的基于脂质的制剂在绝对口服生物利用度方面提供了六至八倍的改善。这些数据表明分散的基于脂质的制剂用于Hf游离碱和潜在的其它亲脂性药物的口服递送的效用。(C)1998 Elsevier Science B.V.保留所有权利。
The potential for lipidic self-emulsifying drug delivery systems (SEDDS) and self-microemulsifying drug delivery systems (SMEDDS) to improve the oral bioavailability of a poorly absorbed, antimalarial drug (Halofantrine, Hf) was investigated in fasted beagles. Hf free base, rather than the commercially available hydrochloride salt (Hf.HCl), was studied due to its much higher solubility in lipidic triglyceride solvents. The multi-component delivery systems were optimised by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation, and by determination of particle size of the resulting emulsion. Optimised formulations selected for bioavailability assessment were medium-chain triglyceride SEDDS and SMEDDS, and a long-chain triglyceride SMEDDS. The relevant pharmacokinetic parameters of Hf, and its desbutyl metabolite, were determined relative to an intravenous formulation. The lipid-based formulations of Hf base afforded a six- to eight-fold improvement in absolute oral bioavailability relative to previous data of the solid Hf.HCl tablet formulation. These data indicate the utility of dispersed lipid-based formulations for the oral delivery of Hf free base, and potentially other lipophilic drugs. (C) 1998 Elsevier Science B.V. All rights reserved.