Lipid-based intravesical drug delivery systems with controlled release of Trospium chloride (cas 10405-02-4) for the urinary bladder

Add time:08/06/2019    Source:sciencedirect.com

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 (cas 10405-02-4), 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.

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