The effect of sucrose and salts in combination on the drug release behaviour of an HPMC matrix.
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 sol-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 0.35-0.4 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.
Williams
Hywel D
HD
Formulation Insights, School of Pharmacy, University of Nottingham, Nottingham, UK.
Ward
Robert
R
Hardy
Ian J
IJ
Melia
Colin D
CD
D002110:Caffeine / Q000032:analysis / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry; D002951:Citrates / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry; D016503:Drug Delivery Systems; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012492:Salts; D012995:Solubility; D013395:Sucrose / Q000737:chemistry*; D013607:Tablets; D044366:Transition Temperature
D002241:Carbohydrates; D002951:Citrates; D003692:Delayed-Action Preparations; D011108:Polymers; D012492:Salts; D013607:Tablets; C514290:trisodium citrate; D002110:Caffeine; D065347:Hypromellose Derivatives; D013395:Sucrose; D008747:Methylcellulose