title: Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole.
abstract: It was the purpose of this study to design and evaluate a new bioadhesive vaginal drug delivery system for clotrimazole. Chitosan, a cationic biopolymer derived by deacetylation of chitin, was modified by the introduction of thioglycolic acid (TGA). The modification was achieved by utilising a carbodiimide to link the carboxylic acid moieties of TGA covalently to the primary amino groups of chitosan. The amount of added carbodiimide was thereby varied, resulting in chitosan-TGA conjugates A and B with 160 microM (=micromol) and 280 microM thiol groups per gram polymer, respectively. In order to characterise the new polymers the water uptake, the disintegration behaviour, the bioadhesive properties utilising the rotating cylinder method, as well as the release of clotrimazole from tablets based on these derivatives were studied. The water uptake and cohesive properties of vaginal tablets consisting of these new conjugates could be significantly (p<0.05) improved. By adding clotrimazole the disintegration time of the conjugates was prolonged 1.6-fold for conjugate A and even 100-fold for conjugate B. Furthermore, the adhesion on vaginal mucosal tissue could be significantly improved. The addition of clotrimazole had also an impact on the adhesion time of chitosan-TGA conjugate B, which remained 26-times longer on vaginal mucosa than the corresponding unmodified polymer. The immobilisation of thiol groups guarantees a controlled drug release. Results of this study demonstrate that these new chitosan-TGA conjugates are very promising vehicles for the vaginal application of clotrimazole in treatment of mycotic infections.
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, Vienna, Austria.
authors.forename: Constantia E
authors.initials: CE
authors.lastname: Kast
authors.forename: Claudia
authors.initials: C
authors.lastname: Valenta
authors.forename: Martina
authors.initials: M
authors.lastname: Leopold
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000268:Adhesiveness; D000282:Administration, Intravaginal; D001672:Biocompatible Materials / Q000737:chemistry; D002686:Chitin / Q000031:analogs & derivatives / Q000737:chemistry; D048271:Chitosan; D003022:Clotrimazole / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems; D007700:Kinetics; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013607:Tablets
chemical_list: D001672:Biocompatible Materials; D013438:Sulfhydryl Compounds; D013607:Tablets; D002686:Chitin; D048271:Chitosan; D003022:Clotrimazole