Use of coated microtubular halloysite for the sustained release of diltiazem hydrochloride and propranolol hydrochloride

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Halloysite is a naturally occurring microtubular aluminosilicate mineral. The highly water soluble cationic drug, diltiazem HCl, was shown to bind to the polyanionic surfaces of the material to achieve a slight sustained release effect on dissolution testing due to reversible chemisorption and/or hindered release from the drug loaded lumen. A greater sustained release effect was more apparent when the less water soluble cationic drug, propranolol HCl, was examined. Attempts to further delay drug release by loading diltiazem HCl from a polyvinylpyrrolidone solution into the halloysite had little effect. However, a range of cationic polymers, including chitosan cross-linked with glutaraldehyde, was shown to bind to halloysite and was used to achieve significant delayed drug release. Coating with adequate polyethyleneimine was particularly effective at delaying drug release, being dependent on the architecture of the interaction between the polycation and the mineral. When a range of alkyl-2-cyanoacrylate monomers applied from a non-aqueous solvent by an in situ polymerisation procedure was examined, diltiazem HCl loaded halloysite dispersed in poly-iso-butyl cyanoacrylate was found to be the most effective at reducing the burst effect noted with aqueous coating systems.

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