Laboratório de Encapsulamento Molecular e Biomateriais - Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
Int J Pharm. 2011 Dec 12;421(1):24-33. doi: 10.1016/j.ijpharm.2011.09.026. Epub 2011 Sep 22.
Sertraline (SRT) is a widely used antidepressant whose poor solubility in water limits its oral applicability. Thus, the aim of this work was the evaluation of a multi-equilibrium system based on β-cyclodextrin (βCD) and SRT. The inclusion compounds (ICs) were investigated by infrared spectroscopy, isothermal titration calorimetry (ITC) and (1)H and 2D ROESY nuclear magnetic resonance experiments. SRT solubility was predicted in vitro in water and biomimetic fluids. The SRT in presence of βCD at 1:1 and 1:2 molar ratios was more soluble than free SRT in all biomimetics media investigated. The FTIR-HATR showed that βCD νC-O-C stretching band was reduced in presence of SRT, suggesting the interactions between them. Additionally, titration process and Job's plot provided information on the ICs stoichiometry and evidenced the multi-equilibrium coexistence in aqueous solution. According to the ITC, SRT:βCD interaction process was spontaneous and exothermic with a high affinity binding constant (K=14,726 M(-1)). Additionally, the stoichiometry coefficient (n) was 1.63, which was comparable to that found by FITR-HATR. The (1)H and 2D ROESY verified multiple SRT sites included into the host cavity. Theoretical calculations depicted the relative energy of different proposed ICs structures, in which the 1:2 IC was the most stable.
舍曲林（SRT）是一种广泛使用的抗抑郁药，但其在水中的溶解度较差，限制了其口服应用。因此，本工作的目的是评估基于β-环糊精（βCD）和 SRT 的多平衡体系。通过红外光谱、等温滴定微量热法（ITC）和（1）H 和 2D ROESY 核磁共振实验研究了包含化合物（ICs）。预测了 SRT 在水和仿生流体中的体外溶解度。在 1:1 和 1:2 摩尔比下，SRT 与 βCD 的混合物在所有研究的仿生介质中的溶解度均高于游离 SRT。FTIR-HATR 表明，βCD νC-O-C 伸缩带在 SRT 存在下减少，表明它们之间存在相互作用。此外，滴定过程和 Job 图提供了关于 IC 化学计量的信息，并证明了水溶液中多平衡共存。根据 ITC，SRT:βCD 相互作用过程是自发的和放热的，具有高亲和力结合常数（K=14,726 M(-1)）。此外，化学计量系数（n）为 1.63，与 FITR-HATR 发现的值相当。（1）H 和 2D ROESY 证实了多个 SRT 位点被包含在主体空腔中。理论计算描绘了不同提出的 IC 结构的相对能量，其中 1:2 IC 是最稳定的。
