Solubilization and Interaction of Sulindac with β-Cyclodextrin in the Solid State and in Aqueous Solution

• Published in: Drug development and industrial pharmacy 1998-01, Vol.24 (3), p.301-306
• Main Authors: Ilarduya, M. C. Tros de, Martían, C., Goñi, M. M., Martínez-Ohárriz, M. C.
• Format: Article
• Language: English
• Subjects: beta-Cyclodextrins; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chemical Phenomena; Chemistry, Physical; Cyclodextrins; Medical sciences; Pharmacology. Drug treatments; Solubility; Solutions; Spectrophotometry, Ultraviolet; Sulindac - chemistry; X-Ray Diffraction
• ISSN: 0363-9045; 1520-5762
• DOI: 10.3109/03639049809085624

Abstract A sulindac-β-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-β-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 β-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 β-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°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°C was 139 M−1, which indicated that the complex is formed easier with the non-ionized sulindac. The enthalpy change, δH°, showed that the binding process is exothermic.