Preparation, Characterization, and In Vitro Intestinal Permeability Evaluation of Thalidomide–Hydroxypropyl-β-Cyclodextrin Complexes

• Published in: AAPS PharmSciTech Vol. 13; no. 1; pp. 118 - 124
• Main Authors: Kratz, Jadel M., Teixeira, Marina R., Ferronato, Karine, Teixeira, Helder F., Koester, Letícia S., Simões, Cláudia M. O.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2012
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins - chemical synthesis; beta-Cyclodextrins - metabolism; beta-Cyclodextrins - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Caco-2 Cells; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Humans; Intestinal Absorption - drug effects; Intestinal Absorption - physiology; Permeability - drug effects; Pharmacology/Toxicology; Pharmacy; Research Article; Solubility - drug effects; Thalidomide - chemical synthesis; Thalidomide - metabolism; Thalidomide - pharmacology; X-Ray Diffraction; solubility; intestinal permeability; thalidomide; cyclodextrin; dissolution
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-011-9739-2

Thalidomide is emerging as a therapeutic agent with renewed clinical importance, presenting anti-inflammatory, immunomodulatory, and antineoplasic properties. In this work, we studied the complexation of thalidomide with cyclodextrins as a strategy to circumvent the poor aqueous solubility of the drug. Thalidomide–hydroxypropyl-β-cyclodextrin complexes were obtained by kneading method and were characterized by differential scanning calorimetry, powder X-ray diffractometry, and scanning electronic microscopy. The aqueous solubility and in vitro dissolution of thalidomide were significantly improved through the complexation. Physicochemical analysis of the complexes in solid state revealed a decreased crystallinity of the complexed drug in comparison with free thalidomide. Thalidomide was able to dissociate from the complexes and permeates across intestinal epithelial Caco-2 cells with a favorable high permeability profile equivalent to that of the free drug. In summary, the present results suggest that thalidomide–hydroxypropyl-β-cyclodextrin complexes could be regarded as a promising strategy for improving the gastrointestinal absorption of thalidomide.