Investigation on drug solubility enhancement using deep eutectic solvents and their derivatives
Investigation on drug solubility enhancement using deep eutectic solvents and their derivatives
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DOI：
10.1016/j.ijpharm.2016.04.018
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发表时间：
2016-05-30
影响因子：
5.8
通讯作者：
Lee, Ping I.
中科院分区：
文献类型：
--
作者：
Li, Zheng;Lee, Ping I.
深共晶溶剂（DES）是一种室温液体，通常由两种固体化合物混合而成，如季铵盐（QAS）（如氯化胆碱）和氢键供体（HBD）（如尿素或羧酸）。通常，在共晶成分附近也可以得到一系列室温液体。因此，引入一个更通用的术语深度共晶溶剂衍生物（DESDs）来描述包括三元混合物衍生的类深度共晶溶剂衍生物是更方便的。由于DESD组分之间的氢键作用降低了共晶体系组分的晶格能，从而降低了混合物的熔点。通过对22对氯胆碱类DES对的数据分析，我们发现熔点的下降与氢键供体（HBD）组分溶解度参数的氢键贡献（8h）和极性贡献（8p）的差异具有统计学相关性。以乙醇酸和氯化胆碱为原料，以1:1 ~ 1:4的摩尔比形成具有类聚醚性质的新型聚醚，验证了两者之间的相关性。作为室温液体，该DESD对几种弱碱性难水溶性药物具有广泛的溶解性增强作用。例如，伊曲康唑、吡罗昔康、利多卡因和泊沙康唑的溶解度在室温下分别比其水溶液溶解度增加了6700倍、430倍、28倍和6400倍。此外，另一种基于氯化胆碱、乙醇酸和草酸的新型三元DESD以1:1. 16:0.4的摩尔比进一步提高了伊曲康唑的溶解度，达到5.36 mg/mL（增加了53,600倍！）由于这些desd的成分可以包括那些生物可降解的成分，这些成分以前曾用于配制的人类产品，因此合适的desd在药物输送方面的潜在适用性，特别是在增强局部制剂的药物溶解度方面可能非常有吸引力。(C) 2016 Elsevier B.V.版权所有
Deep eutectic solvent (DES) is a room temperature liquid typically formed by mixing two solid compounds, such as a quaternary ammonium salt (QAS) (e.g. choline chloride) and a hydrogen bond donor (HBD) (e.g. urea or a carboxylic acid) at their eutectic composition. Very often, a range of room temperature liquids can also be obtained near the eutectic composition. Hence, it is more convenient to introduce a more general term deep eutectic solvent derivatives (DESDs) to describe a wide range of DES-like derivatives including those derived from ternary mixtures. The melting point of the mixture is lowered because the hydrogen bonding between DESD components reduces the lattice energy of components of the eutectic system. Based on the analysis of available data for 22 such choline chloride-based DES pairs, we found that the observed melting point depression can be statistically correlated with the difference between the hydrogen bonding contribution (8h) and the polar contribution (8p) to the solubility parameter of the hydrogen bond donor (HBD) component. The correlation was validated with a new DESD based on glycolic acid and choline chloride, which form DESDs at a molar ratio between 1:1 and 1:4 with DES-like properties. As a room temperature liquid, this DESD exhibits a wide range of solubility enhancement on several weakly basic poorly water-soluble drugs. For example, the solubility of itraconazole, piroxicam, lidocaine, and posaconazole has been observed to increase by 6700, 430, 28, and 6400-fold, respectively as compared to their aqueous solubility at room temperature. Furthermore, another new ternary DESD based on choline chloride, glycolic acid, and oxalic acid at a molar ratio of 1:1.6:0.4 is shown to further increase the solubility of itraconazole to a remarkable level of 5.36 mg/mL (a 53,600-fold increase!). Because the components of such DESDs can include those biodegradable ones that had previously been used in formulated human products, the potential applicability of suitable DESDs to drug delivery, especially in enhancing drug solubility for topical formulations could be very attractive. (C) 2016 Elsevier B.V. All rights reserved.