title: Development and in vitro evaluation of a buccal drug delivery system based on preactivated thiolated pectin.
abstract: The aim of this study was to evaluate the potential of preactivated thiolated pectin (Pec-Cys-MNA) for buccal drug delivery. Therefore, a gel formulation containing this novel polymer and the model drug lidocaine was prepared and investigated in vitro in terms of rheology, mucoadhesion, swelling behavior and drug release in comparison to formulations based on pectin (Pec) and thiolated pectin (Pec-Cys). Both pectin derivatives showed gel formation without addition of any other excipient due to self-crosslinking thiol groups. Under same conditions, pectin did not show gel formation. Viscosity of Pec-Cys-based formulation increased 92-fold and viscosity of Pec-Cys-MNA-based formulations by 4958-fold compared to pectin-based formulation. Gels did not dissolve in aqueous environment during several hours and were able to take up water. Mucoadhesion of pectin on buccal tissue could be improved significantly, value of total work of adhesion increased in the following rank order: Pec-Cys-MNA > Pec-Cys > Pec. The retention time of a model drug incorporated in gel formulations on buccal mucosa under continuous rinsing with phosphate-buffered saline was prolonged, after 1.5 h 3-fold higher amount of a model drug was to be found on tissue after application of Pec-Cys-MNA-based formulation compared to pectin-based and 2-fold compared to Pec-Cys-based formulation. The Pec-Cys-MNA-based gel showed a more sustained release of lidocaine than Pec-Cys-based gel, whereas pectin solution revealed an immediate release. According to these results, the self-crosslinking pectin-derivative is a promising tool for buccal application.
authors.affiliation: Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Center for Molecular Biosciences, Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hauptstein
authors.forename: Fabian
authors.initials: F
authors.lastname: Hintzen
authors.forename: Christiane
authors.initials: C
authors.lastname: Müller
authors.forename: Moritz
authors.initials: M
authors.lastname: Ohm
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical; D003545:Cysteine / Q000737:chemistry*; D016503:Drug Delivery Systems; D005782:Gels / Q000737:chemistry*; D008012:Lidocaine / Q000008:administration & dosage; D009061:Mouth Mucosa; D009539:Nicotinic Acids / Q000737:chemistry*; D010368:Pectins / Q000737:chemistry*; D012212:Rheology; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013552:Swine
chemical_list: D000779:Anesthetics, Local; D005782:Gels; D009539:Nicotinic Acids; D013438:Sulfhydryl Compounds; D010368:Pectins; D008012:Lidocaine; C083470:2-mercaptonicotinic acid; D003545:Cysteine
keywords: Buccal application; gel; lidocaine; pectin; preactivated thiomer