Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 34212, Saudi Arabia.
Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 34212, Saudi Arabia.
AAPS PharmSciTech. 2022 Feb 10;23(2):71. doi: 10.1208/s12249-022-02218-8.
The current investigation was performed with an aim to improve the aqueous solubility, dissolution rate, and thus the biological activity of apigenin (APG) using the solubilizers hydroxypropyl beta-cyclodextrin (HPβCD) and chitosan (CTSN). A binary and ternary inclusion complexes of APG with HPβCD and CTSN were prepared by physical mixing, fusion, and solvent evaporation methods. The liquid state characterization of the APG, the solubilizers, and the physical and chemical interactions between them was done through phase solubility approach. The solid-state characterization was performed by proton nuclear magnetic resonance (1H-NMR), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD). The in vitro dissolution test and antioxidant activity and in vivo anti-inflammatory activity of the ternary inclusion complex in albino rats were performed to assess the performance of the APG. Phase solubility study results revealed a remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HPβCD in presence of CTSN in ternary complex with above 8 folds more increment in solubility of APG than its binary complex. The in vitro dissolution rate, antioxidant activity, and the anti-inflammatory effect of the APG ternary inclusion complex were found to be significantly higher than that of pure APG. Solid state characterization confirmed the formation of a ternary inclusion complex. 1H-NMR study gave more insight at molecular level into how different groups of APG were responsible for complex formation with the HPβCD and how CTSN was significantly influencing on the APG-HPβCD complex formed. Nevertheless, pharmacokinetic and histopathological studies of our APG-HPβCD-CTSN ternary complex would yield much rewarding results.
本研究旨在通过使用增溶剂羟丙基-β-环糊精（HPβCD）和壳聚糖（CTSN）来提高芹菜素（APG）的水溶性、溶解速率，进而提高其生物活性。通过物理混合、熔融和溶剂蒸发法制备了 APG 与 HPβCD 和 CTSN 的二元和三元包合物。通过相溶解度法对 APG、增溶剂及其之间的物理化学相互作用进行了液态特征描述。通过质子核磁共振（1H-NMR）、差示扫描量热法（DSC）和 X 射线衍射法（XRD）进行了固态特征描述。在白化大鼠中进行了三元包合物的体外溶解试验、抗氧化活性和体内抗炎活性研究，以评估 APG 的性能。相溶解度研究结果表明，在三元复合物中存在 CTSN 时，HPβCD 的表观稳定常数（Kc）和络合效率（CE）显著增加，APG 的溶解度比二元复合物增加了 8 倍以上。APG 三元包合物的体外溶解速率、抗氧化活性和抗炎作用明显高于纯 APG。固态特征描述证实了三元包合物的形成。1H-NMR 研究在分子水平上进一步证实了 APG 的不同基团如何与 HPβCD 形成络合物，以及 CTSN 如何显著影响形成的 APG-HPβCD 络合物。然而，我们的 APG-HPβCD-CTSN 三元复合物的药代动力学和组织病理学研究将产生更有价值的结果。
