Polymer-cysteamine conjugates: new mucoadhesive excipients for drug delivery?
In the present study, the features of two new thiolated polymers--the so-called thiomers--were investigated. Mediated by a carbodiimide cysteamine was covalently attached to sodium carboxymethylcellulose (Na-CMC) and neutralised polycarbophil (Na-PCP). Depending on the weight-ratio polymer to cysteamine during the coupling reaction, the resulting CMC-cysteamine conjugate and PCP-cysteamine conjugate showed in maximum 43 +/- 15 and 138 +/- 22 micromole thiol groups per g polymer (mean +/- S.D.; n=3), respectively, which were used for further characterisation. Tensile studies carried out with the CMC-cysteamine conjugate on freshly excised porcine intestinal mucosa displayed no significantly (P<0.01) improved mucoadhesion, whereas, the mucoadhesive properties of the PCP-cysteamine conjugate were increased 2.5-fold compared with the unmodified polymer. The swelling behaviour of the CMC-cysteamine conjugate was uninfluenced by the covalent attachment of the sulfhydryl compound. In contrast the swelling behaviour of the PCP-cysteamine conjugate was improved significantly (P<0.01) versus unmodified PCP. Furthermore, in aqueous solutions the disintegration time of tablets based on the CMC- and PCP-cysteamine conjugates was prolonged 1.5 and 3.2-fold, respectively, in comparison to tablets containing the corresponding unmodified polymers. According to these results, especially the PCP-cysteamine conjugate represents a promising new pharmaceutical excipient for various drug delivery systems.
Kast
Constantia E
CE
Centre of Pharmacy, Institute of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
Bernkop-Schnürch
Andreas
A
D000180:Acrylic Resins / Q000737:chemistry; D000269:Adhesives / Q000737:chemistry*; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D003543:Cysteamine / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D009092:Mucous Membrane / Q000378:metabolism; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013607:Tablets; D013718:Tensile Strength
D000180:Acrylic Resins; D000269:Adhesives; D004337:Drug Carriers; D011108:Polymers; D013438:Sulfhydryl Compounds; D013607:Tablets; D003543:Cysteamine; C030312:calcium polycarbophil; D002266:Carboxymethylcellulose Sodium