Cyclodextrins in nasal drug delivery.
Nasal drug delivery is an attractive approach for the systemic delivery of high potency drugs with a low oral bioavailability due to extensive gastrointestinal breakdown and high hepatic first-pass effect. For lipophilic drugs nasal delivery is possible if they can be dissolved in the dosage form. Peptide and protein drugs often have a low nasal bioavailability because of their large size and hydrophilicity, resulting in poor transport properties across the nasal mucosa. Cyclodextrins are used to improve the nasal absorption of these drugs by increasing their aqueous solubility and/or by enhancing their nasal absorption. With several cyclodextrins very efficient nasal drug absorption has been reported, but also large interspecies differences have been found. Studies concerning the safety of cyclodextrins in nasal drug formulations demonstrate the non-toxicity of the cyclodextrins and also clinical data show no adverse effects. Therefore, some cyclodextrins can be expected to become effective and safe excipients in nasal drug delivery.
Merkus
FW
Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands
Verhoef
JC
Marttin
E
Romeijn
SG
van der Kuy PH
Hermens
WA
Schipper
NG