title: Lipid-based intravesical drug delivery systems with controlled release of trospium chloride for the urinary bladder.
abstract: The overactive bladder (OAB) is a common disease with an overactivity of the detrusor muscle in the bladder wall. Besides peroral administration of anticholinergic drugs and bladder irrigations, there is a need for a sustained release formulation in the urinary bladder. In order to realise a local long-term treatment of the overactive urinary bladder, lipidic drug delivery systems were prepared. Requirements for an intravesical application are a long-term controlled release of trospium chloride, a high drug loading and small sized drug carriers to permit an insertion through the urethra into the urinary bladder. The drug delivery systems were manufactured by using compression (mini-tablets), solid lipid extrusion (extrudates) and a melting and casting technique (mini-moulds) with different amounts of trospium chloride and glyceryl tristearate as matrix former. Drug release depended on the drug loading and the preparation method. Mini-tablets and lipidic extrudates showed a drug release over five days, whereas that from mini-moulds was negligibly small. The appearance of polymorphic transformations during processing and storage was investigated by using differential scanning calorimetry and X-ray diffraction. In contrast to mini-tablets and mini-moulds, lipidic extrudates showed no polymorphic transformations. In summary, lipids are suitable matrix formers for a highly water-soluble drug, like trospium chloride. Despite a drug loading of up to 30%, it was feasible to achieve a drug release ranging from several days up to weeks. In addition, small dosage forms with a size of only a few millimetres were realised. Therefore, an insertion and excretion through the urethra is possible and the requirements for an intravesical application are fulfilled.
authors.affiliation: Department of Urology, RWTH University Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. meike.haupt@hhu.de
authors.forename: M
authors.initials: M
authors.lastname: Haupt
authors.forename: M
authors.initials: M
authors.lastname: Thommes
authors.forename: A
authors.initials: A
authors.lastname: Heidenreich
authors.forename: J
authors.initials: J
authors.lastname: Breitkreutz
mesh_terms: D001561:Benzilates / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems; D009662:Nortropanes / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D013228:Stearates / Q000737:chemistry; D013607:Tablets; D001743:Urinary Bladder; D064804:Urological Agents / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D001561:Benzilates; D003692:Delayed-Action Preparations; D009662:Nortropanes; D013228:Stearates; D013607:Tablets; D064804:Urological Agents; C003330:trospium chloride
keywords: Intravesical drug delivery; Mini-mould; Mini-tablet; Overactive bladder; Solid lipid extrusion; Trospium chloride