title: Preparation, characterization, and in vitro intestinal permeability evaluation of thalidomide-hydroxypropyl-β-cyclodextrin complexes.
abstract: 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.
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina-UFSC, Florianópolis, SC, Brazil.
authors.forename: Jadel M
authors.initials: JM
authors.lastname: Kratz
authors.forename: Marina R
authors.initials: MR
authors.lastname: Teixeira
authors.forename: Karine
authors.initials: K
authors.lastname: Ferronato
authors.forename: Helder F
authors.initials: HF
authors.lastname: Teixeira
authors.forename: Letícia S
authors.initials: LS
authors.lastname: Koester
authors.forename: Cláudia M O
authors.initials: CM
authors.lastname: Simões
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D010539:Permeability / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D013792:Thalidomide / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D013792:Thalidomide