title: Hydrophilic and hydrophobic cyclodextrins in a new sustained release oral formulation of nicardipine: in vitro evaluation and bioavailability studies in rabbits.
abstract: The feasibility of using complexes with cyclodextrins (CDs) in nicardipine (NC) controlled delivery has been examined, with a view to extending the pharmaceutical applications spectrum of these carriers. For a fast release fraction, a hydrophilic beta-cyclodextrin derivative (hydroxypropyl-beta-cyclodextrin) was employed to form a water-soluble complex. For the sustained-releasing portion, triacetyl-beta-cyclodextrin (TAbetaCD) was used to provide complexes with appropriate hydrophobicity. An optimal formulation was designed by the combination of each fraction in different mixing ratios. The release behaviour of the complexes, as well as of their mixtures, was examined in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids. The formulations released the drug rapidly at the initial stage, followed by a slow release. The drug release rate was markedly retarded in the increasing order of the amount of NC/TAbetaCD complex. When NC was administered to rabbits, its absorption was very rapid with a short elimination half-life, while a prolonged maintenance of the plasma levels was obtained for the two selected formulations. The drug bioavailability was considerably improved especially after the administration of the mixture of hydrophilic and hydrophobic complexes, when compared with the NC/TAbetaCD complex. The results suggested that the critical combination of hydrophilic and hydrophobic CDs complexes, in appropriate ratios, could be a promising drug delivery system with a prolonged therapeutic effect coupled with a more balanced bioavailability.
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Rua do Norte, 3000, Coimbra, Portugal.
authors.forename: Catarina Marques
authors.initials: CM
authors.lastname: Fernandes
authors.forename: Pedro
authors.initials: P
authors.lastname: Ramos
authors.forename: Amílcar Celta
authors.initials: AC
authors.lastname: Falcão
authors.forename: Francisco José Baptista
authors.initials: FJ
authors.lastname: Veiga
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations; D009529:Nicardipine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011817:Rabbits; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D047392:beta-Cyclodextrins
chemical_list: D002121:Calcium Channel Blockers; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D047392:beta-Cyclodextrins; C474090:triacetyl-beta-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D009529:Nicardipine