IQUIR-CONICET, Suipacha 570, 2000, Rosario, Argentina.
Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000, Rosario, Argentina.
Drug Deliv Transl Res. 2019 Feb;9(1):273-283. doi: 10.1007/s13346-018-0591-8.
This work aimed to synthesize a novel β-cyclodextrin derivative, itaconyl-β-cyclodextrin to evaluate whether albendazole inclusion complexes with the new β-cyclodextrin derivative-improved albendazole dissolution efficiency and its anthelminthic activity. The new derivative was thoroughly evaluated and characterized, and an average degree of substitution of 1.4 per cyclodextrin molecule was observed. Albendazole:itaconyl-β-cyclodextrin complexes were prepared by spray drying procedures and investigated using phase solubility diagrams, dissolution efficiency, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared, scanning electronic microscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Phase solubility diagrams and mass spectrometry studies showed that the inclusion complex was formed in an equimolar ratio. Stability constant values were 602 M in water, and 149 M in HCl 0.1 N. Nuclear magnetic resonance experiments of the inclusion complex showed correlation signals between the aromatic and propyl protons of albendazole and the itaconyl-β-cyclodextrin inner protons. The studies indicated solid structure changes of albendazole included in itaconyl-β-cyclodextrin. The maximum drug release was reached at 15 min, and the inclusion complex solubility was 88-fold higher than that of the pure drug. The in vitro anthelmintic activity assay showed that the complex was significantly more effective than pure albendazole.
本工作旨在合成一种新型的β-环糊精衍生物，即衣康酰基-β-环糊精，以评估阿苯达唑与新型β-环糊精衍生物的包合物是否能提高阿苯达唑的溶解效率及其驱虫活性。对新衍生物进行了全面的评价和表征，观察到每个环糊精分子的平均取代度为 1.4。采用喷雾干燥法制备阿苯达唑：衣康酰基-β-环糊精包合物，并通过相溶解度图、溶解效率、X 射线衍射、差示扫描量热法、傅里叶变换红外光谱、扫描电子显微镜、质谱和核磁共振光谱进行研究。相溶解度图和质谱研究表明，形成了等摩尔比的包合物。在水中稳定常数值为 602 M，在 0.1 N HCl 中为 149 M。包合物的核磁共振实验表明，阿苯达唑的芳基和丙基质子与衣康酰基-β-环糊精内部质子之间存在相关信号。这些研究表明阿苯达唑包含在衣康酰基-β-环糊精中发生了固体结构变化。在 15 分钟时达到最大药物释放，包合物的溶解度比纯药物高 88 倍。体外驱虫活性测定表明，该复合物比纯阿苯达唑更有效。
