The effect of taste masking agents on in situ gelling pectin formulations for oral sustained delivery of paracetamol and ambroxol.
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).
Miyazaki
Shozo
S
Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tohbetsu, Hokkaido 061-0293, Japan.
Kubo
Wataru
W
Itoh
Kunihiko
K
Konno
Yasuhiro
Y
Fujiwara
Mariko
M
Dairaku
Masatake
M
Togashi
Mitsuo
M
Mikami
Ryozo
R
Attwood
David
D
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
D018712:Analgesics, Non-Narcotic; D003692:Delayed-Action Preparations; D005100:Expectorants; D005421:Flavoring Agents; D019999:Pharmaceutical Solutions; D000551:Ambroxol; D000082:Acetaminophen; D013395:Sucrose; D010368:Pectins