Development of self emulsifying lipid formulations of BCS class II drugs with low to medium lipophilicity
Development of self emulsifying lipid formulations of BCS class II drugs with low to medium lipophilicity
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DOI：
10.1016/j.ijpharm.2015.09.009
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发表时间：
2015-11-10
影响因子：
5.8
通讯作者：
Demarne, Frederic
中科院分区：
文献类型：
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作者：
Jannin, Vincent;Chevrier, Stephanie;Demarne, Frederic
基于脂质的制剂可以是水溶性较差的化学实体的有效的药物递送系统，只要它们的设计与辅料的精心选择，基于它们在递送系统中的作用和与药物性质的关系。导致生物利用度增加的主要因素是在预溶状态下给药，从而避免溶出限制步骤。所有被测试的模型药物（吡罗西康、姜黄素和硝苯地平）都属于同一个化学空间——小的BCS II类分子，logp范围从2到3。这些药物，表现为低至中等对数P，不溶于亲脂性脂基赋形剂（如植物油）。水溶性和水分散表面活性剂能够将每种药物的目标剂量溶解在剂型中，并在分散过程中有效地保持在溶液中。体外消化试验是必要的，以区分配方，使选择最稳健的一个。对于每个分子，在分散/消化测试中表现最佳的体系并不包含为药物提供最高溶剂容量的表面活性剂。这项研究证明了基于表面活性剂的配方的潜力-即脂质配方分类系统中的IV型系统-用于这种类型的疏水药物。(C) 2015 Elsevier B.V.版权所有
Lipid-based formulations can be effective drug delivery systems for poorly water-soluble chemical entities, provided they are designed with careful selection of the excipients, based on their role in the delivery system and in relation to drug properties. The primary factor leading to increased bioavailability is the administration of the drug in a pre-dissolved state thereby avoiding the dissolution limiting step. All model drugs tested (piroxicam, curcumin and nifedipine) belong to the same chemical space-small BCS class II molecules with log P ranging from 2 to 3. These drugs, exhibiting low to medium log P, are not soluble in lipophilic lipid-based excipients (e.g., vegetable oils). Water-soluble and water-dispersible surfactants are able to dissolve the target dose of each drug in the dosage form and efficiently keep it in solution during dispersion. In vitro digestion testing was necessary to discriminate formulations and enable selection of the most robust one. For each molecule, the system with the best performance during dispersion/digestion tests did not comprise the surfactant which delivered the highest solvent capacity for the drug. This study demonstrates the potential of surfactant-based formulations - i.e., Type IV systems from the lipid formulation classification system - for this type of hydrophobic drug. (C) 2015 Elsevier B.V. All rights reserved.