In-Situ Forming Polyester Implants for Sustained Intravesical Oxybutynin Release

Background/Objectives: Neurogenic detrusor overactivity (NDO), caused by spinal cord injury or multiple sclerosis, is marked by involuntary bladder contractions and reduced urine volume. Current therapy requires frequent catheterization with oxybutynin hydrochloride. This work investigates a novel in situ forming implant (ISFI) with PLGA as a sustained-release formulation for the urinary bladder by quantifying drug release, polymer degradation, and solvent release in vitro. Methods/Results: Various formulation parameters were investigated, of which the drug load and PLGA termination were found to have the highest impact on drug release and polymer degradation. An increase in drug load from 1.5% to 7.5% for implants with the ester-terminated PLGA enhanced the degradation from 0% to around 20% after 7 d. Oxybutynin base catalyzed the polymer degradation, as implants with PLGA 502 and 15% drug load exhibited a degradation of 33% compared to 0% for 1.5% drug load. In the case of 1.5% drug load, the degradation could be increased by the use of an acid-terminated PLGA, compared to an ester-terminated. Conclusion: In summary, the feasibility of a biodegradable ISFI for NDO patients was shown, which could allow a single administration up to approx. one week, improving the quality of life for NDO patients. Additionally, this work provided insight to which formulation parameters can help to parallel drug release and polymer degradation.