Preparation and characterisation of thiolated poly(methacrylic acid)–starch compositions

• Published in: European journal of pharmaceutics and biopharmaceutics 2004-03, Vol.57 (2), p.219-224
• Main Authors: Bernkop-Schnürch, Andreas, König, Verena, M. Leitner, Verena, H. Krauland, Alexander, Brodnik, Isabella
• Format: Article
• Language: English
• Subjects: Mucoadhesion; Oral drug delivery; Poly(methacrylic acid); Polymethacrylic Acids - chemical synthesis; Polymethacrylic Acids - pharmacokinetics; Starch; Starch - chemical synthesis; Starch - pharmacokinetics; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - pharmacokinetics; Thiolated polymers
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2002.11.001

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 μmol 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 μJ 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.