Ventura Cinzia Anna, Giannone Ignazio, Paolino Donatella, Pistarà Venerando, Corsaro Antonino, Puglisi Giovanni
Pharmaco-Chemical Department, Faculty of Pharmacy, University of Messina, Viale Annunziata, I-98168 Messina, Italy.
Eur J Med Chem. 2005 Jul;40(7):624-31. doi: 10.1016/j.ejmech.2005.03.001. Epub 2005 Apr 2.
The ability of 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-Cyd) to include the anti-inflammatory drug celecoxib (CCB) was evaluated. The complex was prepared by kneading and freeze-drying methods and was characterized in the solid state and in aqueous solution. Water solubility and dissolution rate of CCB, in a medium simulating gastric fluid, significantly increased after complexation, with complete dissolution obtained after 30 and 180 min for the freeze-dried and kneaded complexes respectively. Phase solubility studies showed Ap-type diagrams. Stability constants for the 1:1 and 1:2 CCB-DM-beta-Cyd complexes and (1)H-NMR studies suggested a probable 1:1 inclusion complex and only an external interaction for the second Cyd molecule. Thermodynamic parameters of the binding process showed the existence of van der Waals forces between CCB and DM-beta-Cyd. DM-beta-Cyd influenced the permeation of CCB through the CaCo-2 cells monolayer. The increase of permeation observed was due to the fast dissolution rate of the included drug and to a destabilizing action exerted by the macrocycle on the biomembrane.
评估了2,6-二-O-甲基-β-环糊精（DM-β-Cyd）包合抗炎药物塞来昔布（CCB）的能力。通过捏合和冷冻干燥法制备该复合物，并对其固态和水溶液状态进行了表征。在模拟胃液的介质中，CCB与DM-β-Cyd形成复合物后，其水溶性和溶解速率显著提高，冷冻干燥复合物和捏合复合物分别在30分钟和180分钟后完全溶解。相溶解度研究显示为Ap型图。CCB与DM-β-Cyd 1:1和1:2复合物的稳定常数以及（1）H-NMR研究表明可能形成1:1包合物，且第二个环糊精分子仅存在外部相互作用。结合过程的热力学参数表明CCB与DM-β-Cyd之间存在范德华力。DM-β-Cyd影响CCB透过CaCo-2细胞单层的渗透。观察到的渗透增加是由于包合药物的快速溶解速率以及大环对生物膜施加的去稳定作用。
