Paralleled Polymer Degradation and Oxybutynin Release from Short-Chain Polyesters for In-Situ Forming Intravesical Implant Design.

Abstract

In situ forming implants (ISFI) for intravesical drug delivery represent a promising alternative to current treatment options for neurogenic detrusor overactivity (NDO). Previous formulations demonstrated opportunities for further optimization regarding the temporal alignment between drug release and polymer degradation, which may influence depot persistence during repeated administration. Therefore, different polyester grades with various molecular weights and solvent systems were investigated in order to parallel drug release and polymer degradation. Reducing the molecular weight from 38 to 2 kDa increased degradation threefold (from 8 to 25% within 72 h). Nevertheless, ISFI with PLGA 2 k were characterized by a high initial drug release of 20% after 24 h. By an increase of application frequency from once every nine days to every third day, the initial drug release was reduced to 10% within the first three days paralleling drug release and polymer degradation (10% after 72 h), resulting in a nearly linear relationship between these processes. These findings demonstrate that dose-splitting can effectively modulate release kinetics, supporting improved temporal alignment of drug release and polymer degradation without substantially increasing burst release. In addition, with a low molecular weight polyester grade, depot persistence may be further reduced under repeated administration conditions. Still, an ISFI administered every three days can distinctly improve the quality of life for NDO patients currently administering up to five doses daily.

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