Comparative dissolution studies of 3D-printed inserts in a novel biopharmaceutical bladder model.

Urinary tract disorders come at great discomfort to the patients suffering from them. To treat them, several potent drug substances are available but unfortunately, systemic drug therapy often comes along with undesired adverse effects. Previous work has therefore been conducted aiming at a local drug release in the urinary bladder. However, whether a therapeutically relevant drug concentration may be reached at the target site is not easy to determine when applying common compendial dissolution methods. Therefore, the aim of this study was to develop a biorelevant dissolution model able to take physiological conditions into consideration, i.e. urine flow rates, urination intervals and movement patterns during day- and nighttime. The newly developed bladder model was tested with 3D-printed intravesical inserts containing three different APIs (lidocaine hydrochloride, trospium chloride and hydrochlorothiazide) and varying the operating conditions. Although the cumulative drug release was similar to the compendial method in most cases, notable differences became apparent in the corresponding concentration profiles of all APIs. It revealed periodic concentration fluctuations in 24 h intervals due to the constantly changing volume and agitation in the bladder model. The model furthermore allowed investigating the influence of varying physiological and pathophysiological conditions on local drug release.