Preparation and characterisation of thiolated poly(methacrylic acid)-starch compositions.
The development of mucoadhesive polymer systems, which start swelling in the intestine after oral administration without an enteric coating, might be the key for drug delivery systems exhibiting a prolonged intestinal residence time. The preparation and characterisation of such polymeric excipients was therefore the aim of this study. A poly(methacrylic acid)-cysteine conjugate (thiolated PMAA) exhibiting 747.8+/-30.9 micromol thiol groups per gram polymer was co-precipitated with starch at pH 3. The resulting thiolated PMAA-starch composition consisting of 24% thiolated PMAA and 76% starch was lyophilised and analysed with regard to its swelling behaviour as well as to its cohesive and mucoadhesive properties. Results demonstrated that the thiolated PMAA-starch composition does not swell at all in a simulated gastric fluid. In contrast, a 4- and 6-fold increase in weight by water uptake was observed at pH 5 and 7, respectively. Disintegration studies demonstrated improved cohesive properties due to the immobilisation of thiol groups on PMAA, which are involved in the formation of stabilising inter- and/or intrachain disulfide bonds. Tensile studies demonstrated a total work of adhesion of 90.2+/-15.2 and 27.5+/-2.9 microJ for thiolated PMAA-starch and PMAA-starch, respectively. These results were confirmed by mucoadhesion studies utilising the rotating cylinder method. Thiolated PMAA-starch represents therefore a promising novel mucoadhesive excipient, which might provide a prolonged residence time of various delivery systems in the intestine.
Bernkop-Schnürch
Andreas
A
Center of Pharmacy, Institute of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria. andreas.bernkop-schnuerch@univie.ac.at
König
Verena
V
Leitner
Verena M
VM
Krauland
Alexander H
AH
Brodnik
Isabella
I
D011109:Polymethacrylic Acids / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013213:Starch / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics
D011109:Polymethacrylic Acids; D013438:Sulfhydryl Compounds; C030613:polymethacrylic acid; D013213:Starch