polidocanol and betadex

Depression is a common mental disorder. More than 350 million people of all ages suffer from depression worldwide. Although a number of antidepressants are available, >20% of patients with major depressive disorder suffer from treatment-resistant depression. Therefore, development of novel therapeutics to overcome this condition is required. We reported that intracerebroventricular administration of glucagon-like peptide-2 (GLP-2) exerts antidepressant-like effects treated with or without adrenocorticotropic hormone. In the present study, we developed a nasal formulation of GLP-2 containing 5% polyoxyethylene (25) lauryl ether and 1% β-cyclodextrin that enhanced the resistance of GLP-2 to inactivation by dipeptidyl peptidase-4. Intranasal administration of this formulation (60μg/kg) increased the delivery of GLP-2 to the brain and had antidepressant-like effects on rats. These results suggest the potential of the GLP-2 nasal formulation for use as a novel antidepressant.

Topics: Administration, Intranasal; Animals; Antidepressive Agents; beta-Cyclodextrins; Chemistry, Pharmaceutical; Dipeptidyl Peptidase 4; Glucagon-Like Peptide 2; Male; Polidocanol; Polyethylene Glycols; Rats; Rats, Wistar

The possible competitive displacement of a drug from its cyclodextrin-based inclusion complex by a third substance was investigated by studying the dissolution behaviour of tolbutamide-beta-cyclodextrin inclusion complex in demineralised water and in aqueous solution of different surfactants. Physical mixtures and kneaded systems were prepared in 1:1 and 1:2 drug-beta-cyclodextrin mol/mol ratios and they were characterised by hot-stage microscopy, differential scanning calorimetry, and X-ray powder diffractometry. The release behaviour of tolbutamide from its inclusion complex was studied by studying the dissolution of the binary systems in water and in aqueous solutions of three surfactants: polysorbate 20, poloxyl 23-lauryl ether, and sodium lauryl sulphate. When demineralised water was used as the dissolution media, the fastest dissolution of tolbutamide was obtained from 1:2 kneaded system followed by 1:1 kneaded system. The presence of poloxyl 23-lauryl ether and sodium lauryl sulphate in the media caused a decrement in the rate and extent of dissolution of the drug from both kneaded systems in comparison with that obtained from the same systems in water. However, the release of tolbutamide from the kneaded systems remains unaffected when polysorbate 20 was present in the dissolution media. Results of this study suggest that the simultaneous presence of beta-cyclodextrin and surfactants of proper molecular structure in a pharmaceutical formulation can give rise to an unexpected dissolution of the drug.

Topics: beta-Cyclodextrins; Calorimetry, Differential Scanning; Cyclodextrins; Dosage Forms; Polidocanol; Polyethylene Glycols; Polysorbates; Sodium Dodecyl Sulfate; Solubility; Solutions; Surface-Active Agents; Thermodynamics; Tolbutamide; Water; X-Ray Diffraction