title: The effect of taste masking agents on in situ gelling pectin formulations for oral sustained delivery of paracetamol and ambroxol.
abstract: The aim of this study was to examine the influence of polyhydric alcohols (taste masking agents) on the rheological properties of in situ gelling pectin formulations and on the in vitro and in vivo release of paracetamol and ambroxol from these formulations. Gelation of orally administered pectin solutions containing calcium in complexed form occurred on release of calcium in the acidic environment of the stomach. Inclusion of 10% (w/v) sorbitol in 2% (w/v) pectin sols reduced the viscosity and ensured Newtonian flow properties. Xylitol and mannitol in similar concentrations were less effective in reducing viscosity; sucrose increased viscosity and caused non-Newtonian flow. The in vitro release of paracetamol from 2% (w/v) pectin gels formulated with 10% (w/v) of sorbitol, erythritol, xylitol or mannitol, and of ambroxol from 2% (w/v) pectin gels containing 10% (w/v) sorbitol, followed diffusion-controlled kinetics. Pectin gels (2%, w/v) containing sorbitol (10%, w/v) sustained the release of paracetamol in the rat stomach and bioavailabilities of approximately 90% of those from an orally administered paracetamol syrup were achieved. Sustained release of ambroxol from in situ gelling formulations was achieved with pectin concentrations of 1.5 and 1% (w/v) and a sorbitol concentration of 10% (w/v).
authors.affiliation: Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tohbetsu, Hokkaido 061-0293, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Kubo
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Konno
authors.forename: Mariko
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Masatake
authors.initials: M
authors.lastname: Dairaku
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Togashi
authors.forename: Ryozo
authors.initials: R
authors.lastname: Mikami
authors.forename: David
authors.initials: D
authors.lastname: Attwood
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000551:Ambroxol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005100:Expectorants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005421:Flavoring Agents / Q000737:chemistry*; D008297:Male; D010368:Pectins / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000737:chemistry; D014783:Viscosity
chemical_list: D018712:Analgesics, Non-Narcotic; D003692:Delayed-Action Preparations; D005100:Expectorants; D005421:Flavoring Agents; D019999:Pharmaceutical Solutions; D000551:Ambroxol; D000082:Acetaminophen; D013395:Sucrose; D010368:Pectins