PDF(Pubmed)
Abstract：
Generally, NSAIDs are weakly soluble in water and contain both hydrophilic and hydrophobic groups. One of the most widely used NSAIDs is ibuprofen, which has a poor solubility and high permeability profile. By creating dynamic, non-covalent, water-soluble inclusion complexes, cyclodextrins (CDs) can increase the dissolution rate of low aqueous solubility drugs, operating as a drug delivery vehicle, additionally contributing significantly to the chemical stability of pharmaceuticals and to reducing drug-related irritability. In order to improve the pharmacological and pharmacokinetics profile of ibuprofen, new thiazolidin-4-one derivatives of ibuprofen (4b, 4g, 4k, 4m) were complexed with β-CD, using co-precipitation and freeze-drying. The new β-CD complexes (β-CD-4b, β-CD-4g, β-CD-4k, β-CD-4m) were characterized using scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and a phase solubility test. Using the AutoDock-VINA algorithm included in YASARA-structure software, we investigated the binding conformation of ibuprofen derivatives to β-CD and measured the binding energies. We also performed an in vivo biological evaluation of the ibuprofen derivatives and corresponding β-CD complexes, using analgesic/anti-inflammatory assays, as well as a release profile. The results support the theory that β-CD complexes (β-CD-4b, β-CD-4g, β-CD-4k, β-CD-4m) have a similar effect to ibuprofen derivatives (4b, 4g, 4k, 4m). Moreover, the β-CD complexes demonstrated a delayed release profile, which provides valuable insights into the drug-delivery area, focused on ibuprofen derivatives.
摘要：
一般来说,NSAID在水中是弱溶解的并且含有亲水和疏水基团。最广泛使用的NSAIDs之一是布洛芬，其具有差的溶解度和高的渗透性。通过创建动态，非共价的,水溶性包合物，环糊精（CD）可以提高低水溶性药物的溶出度，作为药物输送工具，此外，显着有助于药物的化学稳定性和减少药物相关的烦躁。为了改善布洛芬的药理和药代动力学特征，布洛芬的新噻唑烷-4-酮衍生物（4b，4g,4k,4m)与β-CD络合，使用共沉淀和冷冻干燥。新的β-CD复合物（β-CD-4b，β-CD-4g,β-CD-4k,β-CD-4m）使用扫描电子显微镜（SEM）进行表征，差示扫描量热法(DSC),X射线衍射和相溶解度测试。使用YASARA结构软件中包含的AutoDock-VINA算法，我们研究了布洛芬衍生物与β-CD的结合构象并测量了结合能。我们还对布洛芬衍生物和相应的β-CD复合物进行了体内生物学评估，使用镇痛/抗炎试验，以及发布简介。结果支持β-CD复合物(β-CD-4b，β-CD-4g,β-CD-4k,β-CD-4m)与布洛芬衍生物(4b，4g,4k,4m)。此外，β-CD复合物表现出延迟释放曲线，这提供了对药物输送领域的宝贵见解，专注于布洛芬衍生物。
