Abstract
Background/Objectives: Silodosin (SLD) is a selective α1A-adrenoceptor antagonist used in the treatment of benign prostatic hyperplasia. Bioequivalence failures have been reported for hard capsule formulations, largely due to the effect of disintegrant excipients, making soft capsules a promising alternative dosage form. This study investigated the stability of SLD soft capsules stored in two different packaging materials, PVC/PVDC and AquaBa(®). Methods: Storage temperatures at 25 °C/60%, 30 °C/65% RH, 30 °C/75% RH, and 40 °C/75% RH, and sampling were performed according to the International Council for Harmonisation (ICH) stability conditions. Assays were performed by HPLC and UV, and mass detection. Results: Degradation analysis revealed that temperature played a critical role in SLD degradation and the formation of its primary degradation products, dehydrosilodosin and impurity 1. Conclusions: AquaBa(®) demonstrated superior protective properties compared to PVC/PVDC, preserving SLD content above 95% for over 12 months under 25 °C and 30 °C conditions while limiting the formation of degradation products. Nevertheless, impurity 1 exceeded its ICH Q3B (R2) specification limit (0.3%) after six months under all conditions tested, suggesting a critical interaction between SLD and excipients such as Capryol(®) 90. Kinetic modeling confirmed first-order degradation kinetics for both dehydrosilodosin and impurity 1, with a faster degradation rate observed in PVC/PVDC blisters. These findings highlight the critical role of packaging in pharmaceutical stability. While AquaBa(®) emerges as the preferred option for SLD soft capsules, formulation optimization remains necessary to limit impurity formation, extend shelf life, and ensure regulatory compliance.