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 mumol 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 muJ 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. (C) 2004 Elsevier B.V. All rights reserved.