TY - JOUR
T1 - The effect of sucrose and salts in combination on the drug release behaviour of an HPMC matrix
AU - Williams, Hywel
AU - Ward, Robert
AU - Hardy, Ian
AU - Melia, Colin
PY - 2010
Y1 - 2010
N2 - Previous work has shown how high concentrations of sugars can accelerate drug release from hydroxypropyl
methylcellulose (HPMC) matrices by suppressing polymer hydration. This study investigates the
effects of combining sugar and salts, using sucrose, sodium chloride and trisodium citrate, soluble ingredients
commonly found in foods. A factorial study showed that each solute suppressed HPMC solution
sola??gel transition temperature (a sensitive measure of molecular hydration) independently, and their
effects reflected their rank order in the Hofmeister series. In mixtures, the effects were purely additive,
with no evidence of antagonism or synergy. In dissolution tests, both salts significantly reduced the
threshold sugar concentration required to elicit an acceleration of drug release, and when used in combination,
0.15 M sodium chloride with 0.015 M trisodium citrate reduced the threshold sucrose concentration
from 0.7 M to 0.35a??0.4 M, a reduction of almost 50 . The results show that food salts can
significantly reduce the concentration required for sugar effects on HPMC matrices, and this may be a factor
to consider when interpreting their in vivo behaviour in the fed state.
AB - Previous work has shown how high concentrations of sugars can accelerate drug release from hydroxypropyl
methylcellulose (HPMC) matrices by suppressing polymer hydration. This study investigates the
effects of combining sugar and salts, using sucrose, sodium chloride and trisodium citrate, soluble ingredients
commonly found in foods. A factorial study showed that each solute suppressed HPMC solution
sola??gel transition temperature (a sensitive measure of molecular hydration) independently, and their
effects reflected their rank order in the Hofmeister series. In mixtures, the effects were purely additive,
with no evidence of antagonism or synergy. In dissolution tests, both salts significantly reduced the
threshold sugar concentration required to elicit an acceleration of drug release, and when used in combination,
0.15 M sodium chloride with 0.015 M trisodium citrate reduced the threshold sucrose concentration
from 0.7 M to 0.35a??0.4 M, a reduction of almost 50 . The results show that food salts can
significantly reduce the concentration required for sugar effects on HPMC matrices, and this may be a factor
to consider when interpreting their in vivo behaviour in the fed state.
U2 - 10.1016/j.ejpb.2010.09.001
DO - 10.1016/j.ejpb.2010.09.001
M3 - Article
SN - 0939-6411
VL - 76
SP - 433
EP - 436
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
IS - 3
ER -