Journal
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
Volume 29, Issue 1, Pages 61-69Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1081/DDC-120016684
Keywords
mucoadhesion; chitosan; N-trimethyl chitosan chloride (TMC); size-exclusion chromatography (SEC); multiangle laser light scattering (MALLS); surface-tension analysis; tensile separation testing
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Previous studies have established that N-trimethyl chitosan chloride (TMC) is a potent absorption enhancer for peptides and large hydrophilic compounds across mucosal surfaces, especially in neutral and basic environments where chitosan is ineffective as an absorption enhancer. The degree of quaternization of TMC plays an important role on its absorption-enhancing properties. Several TMC polymers with different degrees of quaternization were synthesized and the molecular mass of the polymers was determined by SEC/MALLS. The mucoadhesive properties of the TMC polymers were measured with a modified tensiometer based on the Willhelmy plate method. The effect of the TMC polymers on the surface tension of a mixture of polymer and mucus was measured with a Du Nouy tensiometer. The degrees of quaternization of the synthesized TMC polymers were between 22.1% and 48.8% and the molecular mass was above 100,000 g/mole for all the polymers. A decrease in mucoadhesivity with an increase in the degree of quaternization of the TMC polymers was found. Surface-tension analysis of a mixture of polymer and mucus showed the effect of excessive polymer hydration on mucoadhesion. The results show that the degree of quaternization of TMC had a pronounced effect on the mucoadhesive properties of this polymer: Although the mucoadhesive profiles for the TMC polymers were lower than the original chitosan, they still retained sufficient mucoadhesive properties for successful inclusion into mucoadhesive dosage forms.
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