Abstract/Summary

In the pharmaceutical industry, excipients such as cellulose and its derivatives are often used in the formulation of dosage forms as binders for tablets, viscosity enhancers, gelling agents, coating agents, etc. In addition to its basic functionality, this polymer can be modified to provide additional properties that optimise its performance in a particular application. An example of properties that are of great interest is mucoadhesion. The mucoadhesive properties allow greater contact between the formulation and the oral mucosa for a slow release of the active ingredient. Among the cellulose derivatives, hydroxyethyl cellulose (HEC) has weak mucoadhesive properties. However, it can be improved by modification with unsaturated groups such as methacryloyl, maleimide, acryloyl and divinyl sulfone. The newly modified HEC can interact with mucin glycoproteins by forming covalent bonds between the electronegative unsaturated end groups of the modified polymer and the less electronegative parts of the mucin glycoprotein (cysteine) via the Michael addition reaction. In this thesis, we have synthesised HEC with methacryloyl, maleimide, acryloyl and divinyl sulfone groups. The successful synthesis of the new polymers was validated using 1H NMR and FTIR. It was further quantified by either 1H NMR, HPLC and/or elemental analysis. These modified polymers were developed into various blank dosage forms (wafers, films, spray-coated tablets and microparticles) to determine their mucoadhesiveness using a texture analyser. A safety study was performed using planarian acute toxicity assays and planarian fluorescent toxicity assays. The safety study was further supported by in vitro toxicity assay using Caco-2 cells. Our findings suggest that synthesis process of all HEC derivatives was successful and regardless of molar ratio, the modified HEC with methacryloyl, maleimide, acryloyl and sulfone groups has improved the mucoadhesiveness of the native HEC. Additionally, the newly modified excipients are water soluble, versatile in dosage form development and easy to synthesis (one-pot synthesis method) under normal environmental conditions. These results support the idea that non-ionic HEC modified with unsaturated groups such as methacryloyl, maleimide, acryloyl and sulfone groups significantly improves the mucoadhesive properties of native HEC. Therefore, modified HEC with methacryloyl, maleimide, acryloyl and sulfone groups has great potential as a new multifunctional excipient for transmucosal drug delivery, as it has the advantage of being mucoadhesive yet retaining the non-ionic nature of HEC derivatives. This may promote greater compatibility with charged drug molecules in dosage form formulations.