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.

Cyclodextrin-polyhydrazine degradable gels for hydrophobic drug delivery

“…This hydrophobic drug has been administered intravenously, subcutaneously and transdermally [32,33]. Formation of inclusion complex with β-CD has been suggested to improve the solubility of NIC in aqueous solution [34,35]. Due to the poor solubility of NIC in aqueous phases and other routes of administration, it has been chosen as a model drug in this work.…”

Pharmacokinetics and bioavailability of a newly synthesized dihydropyridine compound with multidrug resistance reversal activity

“…The compound was rapidly absorbed after oral administration with an absorption rate constant k a of approximately 3.6 h À1 . (AE )-DHP-014 demonstrated a relatively poor oral bioavailability (approximately 8%), which may due to poor solubility of the compound [7,8] and substantial first-pass extraction. It was reported that the two related 1,4-dihydropyridines, nicardipine and nitrendipine undergo extensive first-pass hepatic extraction after oral administration [9].…”

Complex of branched cyclodextrin and lidocaine prolonged the duration of peripheral nerve block

“…These derivatives are strong candidates for functional drug carriers to control the rate and/or time profi le of drug release. In fact, hydrophilic and hydrophobic CyDs modify the release rates of drugs [6,7,12].…”

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small molecules and portions of large compounds, and it is now well known that CyDs possess multifunctional characteristics [6,7]. For instance, drugs encapsulated with CyDs provide more balanced biological activity in oral administration and serve the purpose of prolonged therapeutic effect [6].

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