Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany; Drug Delivery Innovation Center (DDIC), INVITE GmbH, Chempark Building W 32, 51368 Leverkusen, Germany.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Int J Pharm. 2022 Aug 25;624:121984. doi: 10.1016/j.ijpharm.2022.121984. Epub 2022 Jul 5.
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.
尿路疾病会给患者带来极大的不适。为了治疗这些疾病，有几种有效的药物可供选择，但不幸的是，全身药物治疗常常伴随着不良的副作用。因此，以前的工作旨在实现膀胱内的局部药物释放。然而，当应用常见的药典溶解方法时，是否可以在靶部位达到治疗相关的药物浓度并不容易确定。因此，本研究的目的是开发一种能够考虑生理条件的生物相关溶解模型，即尿流率、排尿间隔和白天和夜间的运动模式。新开发的膀胱模型用含有三种不同 API（盐酸利多卡因、托品酸氯和氢氯噻嗪）的 3D 打印膀胱内插入物进行了测试，并改变了操作条件。尽管在大多数情况下，累积药物释放与药典方法相似，但所有 API 的相应浓度曲线都出现了明显的差异。由于膀胱模型中的体积和搅拌不断变化，它揭示了 24 小时间隔的周期性浓度波动。该模型还允许研究生理和病理生理条件变化对局部药物释放的影响。
