Granero Gladys E, Maitre Marcos M, Garnero Claudia, Longhi Marcela R
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. Ciudad Universitaria, 5000 Córdoba, Córdoba, Argentina.
Eur J Med Chem. 2008 Mar;43(3):464-70. doi: 10.1016/j.ejmech.2007.03.037. Epub 2007 Apr 24.
The aim of our work was to develop a multicomponent inclusion complex of acetazolamide (ACZ) in order to investigate the combined effect of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and triethanolamine (TEA) on the solubility of ACZ and its possibility of ophthalmic delivery. Phase solubility study was used to evaluate the complexation in solution at 25 degrees C. Complex formation was also evaluated by comparing the infrared (FT-IR) spectra of the solid complexes with a simple physical mixture containing the same amount of ACZ. FT-IR experiments provided data indicating that the carbonamido group of ACZ is involved in the inclusion process. In vitro release data showed that both formulations, containing the freeze-dried ternary complex and the corresponding simple physical mixture of ACZ with HP-beta-CD and TEA presented the fastest release rate of ACZ. These results suggest that the ACZ-HP-beta-CD-TEA complex represents an effective novel formulation to enhance ACZ solubility in water, turning it promising for ophthalmic administration.
我们工作的目的是开发一种乙酰唑胺（ACZ）的多组分包合物，以研究羟丙基-β-环糊精（HP-β-CD）和三乙醇胺（TEA）对ACZ溶解度的联合影响及其眼部给药的可能性。采用相溶解度研究来评估25℃下溶液中的络合作用。还通过比较固体络合物与含有相同量ACZ的简单物理混合物的红外（FT-IR）光谱来评估络合物的形成。FT-IR实验提供的数据表明ACZ的碳酰胺基团参与了包合过程。体外释放数据表明，含有冻干三元络合物以及ACZ与HP-β-CD和TEA的相应简单物理混合物的两种制剂均呈现出ACZ最快的释放速率。这些结果表明，ACZ-HP-β-CD-TEA络合物是一种有效的新型制剂，可提高ACZ在水中的溶解度，使其有望用于眼部给药。
