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

Abstract

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.

Characterization and In Vitro Evaluation of the Complexes of Posaconazole with β- and 2,6-di-O-methyl-β-cyclodextrin

“…CDs exhibit an important function in the field of supramolecular chemistry, as many types of guest molecules can be accommodated into their cavities (16,17). In addition, CDs have been widely used as encapsulating agents to improve the solubility, dissolution rate, stability, and bioavailability of drug molecules (18,19). Especially, in the cyclodextrins, 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD) shows two obvious advantages than the others: the higher water solubility which can get the better solubilization effect, Electronic supplementary material The online version of this article (doi:10.1208/s12249-016-0497-z) contains supplementary material, which is available to authorized users.…”

Experimental and Computational Studies of Physicochemical Properties Influence NSAID-Cyclodextrin Complexation

“…Several papers have demonstrated CD complexation potential to enhance drug permeability and bioavailability (29,30). Other papers have presented models to predict complexation efficiency with various drugs (31,32,18).…”

In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats

“…Ideal drug candidates should have adequate aqueous solubility and permeability in order to achieve effective concentration in the target tissue (Kratz et al, 2012). In order to evaluate the in vitro intestinal permeability, transport experiments were performed on Caco-2 cells.…”

“…These cells are able to fully polarize into differentiated monolayers, with well-established tight junctions and brush border membrane. They can also express several membrane transporters and metabolizing enzymes, allowing the measurement of functional permeability, both through passive diffusion and active transport (Kratz et al, 2012). The apparent permeability of 6MC was high, with values of magnitude of 10 -5 .…”

“…For the transport experiments, 100,000 cells (passages 113-115) were harvested and seeded on each polycarbonate insert (0.6 cm 2 , 0.4 μm pore size; Millipore, USA), and allowed to grow and differentiate for 21-28 days prior to the experiments, as described previously by Kratz et al (2012).…”