Development of sustained-release drug-loaded intravesical inserts via semi-solid micro-extrusion 3D-printing for bladder targeting

International Journal of Pharmaceutics 2022 Volume 622, Article 121849

Discontinued treatment and non-adherence are oftentimes weaknesses of common first-line drug therapy against bladder conditions due to their negative side-effects. To overcome these limitations and increase patients’ quality of life, intravesical therapies are continuously being explored. 3D-printing offers the possibility of freely tailoring drug delivery systems to manufacture indwelling devices that may administer drugs locally over an extended time and avoiding frequently repeated administrations while minimizing systemic side-effects. In the present work, pressure-assisted micro syringe printing has been used to develop flexible drug-loaded inserts applicable via common urinary catheter that can remain up to several weeks inside the urinary bladder. Three APIs (lidocaine hydrochloride, trospium chloride (TrCl) and hydrochlorothiazide (HCT)) with different properties and solubilities were investigated for their applicability together with two different pharmaceutical polymers (biodegradable polycaprolactone (PCL) and non-degradable ethylene vinyl acetate copolymer (EVA)). The fastest release was thereby observed for the PCL-TrCl combination and the slowest for EVA-HCT depending on the API’s solubility in the dissolution medium and formation of API clusters within the matrix. It was further demonstrated that the dissolution profile could be modified by adapting drug loads between 5 and 15 % or the geometry of the printed inserts indicating the possibility of tailoring release profiles.