A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: Solubility and permeability studies
A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: Solubility and permeability studies
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DOI：
10.1016/j.ejpb.2017.02.003
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发表时间：
2017-05-01
影响因子：
4.9
通讯作者：
Paiva, Alexandre
中科院分区：
文献类型：
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作者：
Duarte, Ana Rita C.;Ferreira, Ana Sofia D.;Paiva, Alexandre
THEDES，即所谓的治疗性深共熔溶剂，在此定义为两种组分的混合物，其在特定摩尔组成下在室温下变为液体，并且其中一种是活性药物成分（API）。在这项工作中，THEDES基于薄荷醇与三种不同的API，布洛芬（ibu），BA（BA）和苯乙酸（PA）的络合物，制备。通过NMR研究了构成THEDES的组分之间的相互作用，证实了低共熔体系是由薄荷醇和API之间的氢键形成的。通过PFGSE NMR光谱研究THEDES组分的迁移率。据确定，该物种的自扩散遵循与先前观察到的离子液体相同的行为，其中组分通过在由点状热波动产生的上层结构中的空隙之间跳跃而迁移。评价了系统在等渗溶液中的溶解度和渗透性，并通过在Franz池中进行的扩散和渗透性研究建立了与纯API的比较。当在THEDES系统中时，API的溶解度可以提高高达12倍，即对于含有ibu的系统。此外，对于该系统，渗透率计算为14 × 10（-5）cm/s，与纯API相比增加了3倍。除含有PA的系统外，观察到溶解度增加，以及渗透性增加。因此，在这项工作中，我们证明了THEDES作为一种新制剂的效率，通过将分子的物理状态从固体剂量改变为液体系统来提高API的生物利用度。(C)2017爱思唯尔B. V.保留所有权利。
THEDES, so called therapeutic deep eutectic solvents are here defined as a mixture of two components, which at a particular molar composition become liquid at room temperature and in which one of them is an active pharmaceutical ingredient (API). In this work, THEDES based on menthol complexed with three different APIs, ibuprofen (ibu), BA (BA) and phenylacetic acid (PA), were prepared. The interactions between the components that constitute the THEDES were studied by NMR, confirming that the eutectic system is formed by H-bonds between menthol and the API. The mobility of the THEDES components was studied by PFGSE NMR spectroscopy. It was determined that the self-diffusion of the species followed the same behavior as observed previously for ionic liquids, in which the components migrate via jumping between voids in the suprastructure created by punctual thermal fluctuations. The solubility and permeability of the systems in an isotonic solution was evaluated and a comparison with the pure APIs was established through diffusion and permeability studies carried out in a Franz cell. The solubility of the APIs when in the THEDES system can be improved up to 12 fold, namely for the system containing ibu. Furthermore, for this system the permeability was calculated to be 14 x 10(-5) cm/s representing a 3 fold increase in comparison with the pure API. With the exception of the systems containing PA an increase in the solubility, coupled with an increase in permeability was observed. In this work, we hence demonstrate the efficiency of THEDES as a new formulation for the enhancement of the bioavailability of APIs by changing the physical state of the molecules from a solid dosage to a liquid system. (C) 2017 Elsevier B.V. All rights reserved.