Development of a Prolonged-Release Pramipexole Transdermal Patch: In Vitro and In Vivo Evaluation

Abstract

The current study aimed to develop a prolonged-release pramipexole (PPX) transdermal patch for the treatment of Parkinson’s disease. Permeation parameters of PPX were investigated using human cadaver skin. Pramipexole patches were prepared using DURO-TAK® pressure-sensitive-adhesive (PSA) and evaluated for drug stability, drug loading, in vitro drug release, and in vitro permeation through mouse skin. The results indicated that blends of DURO-TAK® 87-2852 and DURO-TAK® 87-2510 were suitable for creating a prolonged-release PPX patch due to their advantages in drug release, drug loading, and stability. The final formulation consisted of 87-2852/87-2510 (70:30), 10% PG, and 15% PPX and showed a cumulative permeation amount of 1497.19 ± 102.90 μg/cm2 with a continuous flux over 6.0 μg/(cm2·h) across human cadaver skin for 7 days. In vivo studies in rats indicated that PPX patch produced a significantly longer (p < 0.001) half-life (t1/2, 75.16 ± 17.37 h) and mean residence time (MRT, 135.89 ± 24.12 h) relative to oral tablets (Sifrol®) and had a relative bioavailability of 51.64 ± 21.32%. Therefore, this study demonstrated the feasibility of developing a prolonged-release PPX patch, which proposed the potential to serve as an alternate to conventional oral tablets and may therefore improve patient compliance.