Oral sustained delivery of ambroxol from in situ-gelling pectin formulations.
Gels formed in situ following oral administration of dilute aqueous solutions of pectin (1.0 and 1.5%, w/v) to rats were evaluated as vehicles for the sustained release of the expectorant drug ambroxol hydrochloride. The solutions contained calcium ions in complexed form, which on release in the acidic environment of the stomach caused gelation of the pectin. In vitro studies demonstrated diffusion-controlled release of ambroxol from the gels over a period of 6 h. A bioavailability of ambroxol of approximately 64% of that of a commercially available formulation could be achieved from gels containing an identical dose of ambroxol formed in situ in the stomachs of rats, with appreciably lower peak plasma levels and a sustained release of drug over a period of at least 6 h. The influence of added sorbitol (17%, w/v) on the rheological and drug release properties of the formulations has been examined.
Kubo
Wataru
W
Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tohbetsu, Hokkaido 061-0293, Japan.
Miyazaki
Shozo
S
Dairaku
Masatake
M
Togashi
Mitsuo
M
Mikami
Ryozo
R
Attwood
David
D
D000551:Ambroxol / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002118:Calcium / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D005100:Expectorants / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D005782:Gels; D008297:Male; D010368:Pectins / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013012:Sorbitol / Q000737:chemistry; D014783:Viscosity
D003692:Delayed-Action Preparations; D005100:Expectorants; D005782:Gels; D000551:Ambroxol; D013012:Sorbitol; D010368:Pectins; D002118:Calcium