Tros de Ilarduya M C, Martín C, Goñi M M, Martínez-Ohárriz M C
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain.
Drug Dev Ind Pharm. 1998 Mar;24(3):301-6. doi: 10.3109/03639049809085624.
A sulindac-beta-cyclodextrin complex was obtained by the coprecipitation method. Kneaded solids and physical mixtures were also prepared. The complex was shown by x-ray powder diffraction to be noncrystalline whereas pure drug and any of the other sulindac-beta-CD system were crystalline. the endothermic peak of sulindac due to the fusion of drug disappeared in DSC thermograms for the coprecipitate product, which confirmed the interaction between sulindac and beta-CD in the solid state. After a 1-year storage drug crystals could not be observed by x-ray diffractometry, which indicated that the complex formed was stable. The complex showed the fastest dissolution rate which might be attributed to the high-energy noncrystalline state and the inclusion complex formation in solution. UV spectra were modified and the apparent solubility of the drug increased with the addition of beta-CD, which confirmed the interaction between sulindac and the ligand in solution. The apparent stability constant, K1:1, for the complex at pH 2 and 25, 30, and 37 degrees C was 340, 220, and 160 M-1, respectively, which confirmed the influence of temperature on the complex stability. The value of K1:1 at pH 6 and 25 degrees C was 139 M-1, which indicated that the complex is formed easier with the non-ionized sulindac. The enthalpy change, delta H degree, showed that the binding process is exothermic.
通过共沉淀法获得了舒林酸-β-环糊精复合物。还制备了捏合固体和物理混合物。X射线粉末衍射显示该复合物为非晶态，而纯药物和其他任何舒林酸-β-环糊精体系均为晶态。共沉淀产物的DSC热谱图中，由于药物熔融产生的舒林酸吸热峰消失，这证实了舒林酸与β-环糊精在固态下的相互作用。储存1年后，X射线衍射法未观察到药物晶体，这表明形成的复合物是稳定的。该复合物显示出最快的溶解速率，这可能归因于高能非晶态以及溶液中包合物的形成。紫外光谱发生了改变，并且随着β-环糊精的加入，药物的表观溶解度增加，这证实了舒林酸与配体在溶液中的相互作用。该复合物在pH 2以及25、30和37℃时的表观稳定常数K1:1分别为340、220和160 M-1，这证实了温度对复合物稳定性的影响。pH 6和25℃时K1:1的值为139 M-1，这表明复合物更容易与非离子化的舒林酸形成。焓变ΔH°表明结合过程是放热的。
