Rodriguez-Perez Ana I, Rodriguez-Tenreiro Carmen, Alvarez-Lorenzo Carmen, Taboada Pablo, Concheiro Angel, Torres-Labandeira Juan J
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain.
J Pharm Sci. 2006 Aug;95(8):1751-62. doi: 10.1002/jps.20661.
Complexation of sertaconazole (SN) with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was characterized by phase-solubility diagram measurements and isothermal calorimetry (ITC) in aqueous medium, and by differential scanning calorimetry (DSC), Raman spectroscopy and X-ray diffractometry in solid state. The strongest interaction was observed at pH 1.2, at which two different 1:1 complexes can be formed depending on the hydrophobic ring of the drug involved in the process. At pH 5.8 and 7.4 the likelihood of 1:2 stoichiometry increases as a consequence of the simultaneous complexation of the nonprotonized imidazolyl and the dichlorophenyl groups. In the presence of 20% HP-beta-CD, SN solubility is enhanced by a factor of 116, 107, and 5 at pH 1.2, 5.8, and 7.4, respectively. Complexation enthalpy recorded by ITC showed the same tendency which confirms the practical interest of this technique for fast screening of the potential of CDs as drug solubilizers. Solubility and dissolution rate of the drug from compacts prepared with freeze-dried complexes were significantly greater than those obtained with SN powder or compacts made with physical blends.
在水介质中，通过相溶解度图测量和等温滴定量热法（ITC），以及在固态下通过差示扫描量热法（DSC）、拉曼光谱和X射线衍射法对舍他康唑（SN）与羟丙基-β-环糊精（HP-β-CD）的络合作用进行了表征。在pH 1.2时观察到最强的相互作用，此时根据参与该过程的药物疏水环可形成两种不同的1:1络合物。在pH 5.8和7.4时，由于未质子化的咪唑基和二氯苯基同时络合，1:2化学计量比的可能性增加。在20% HP-β-CD存在下，SN在pH 1.2、5.8和7.4时的溶解度分别提高了116倍、107倍和5倍。ITC记录的络合焓显示出相同的趋势，这证实了该技术对于快速筛选环糊精作为药物增溶剂潜力的实际意义。用冻干络合物制备的片剂中药物的溶解度和溶出速率显著高于用SN粉末或物理混合物制成的片剂。
