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/cm with a continuous flux over 6.0 μg/(cm·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 (t , 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.

The Dissolution Behavior and Solvent Effect Analysis of Pramipexole in Pure Organic Solvents

“…However, from the results of DSC-TG and micro melting point instrument in this work, the temperature around 399.35 K should be the melting point of pramipexole, which is close to 402.15 K reported by Pu and co-workers. 30 3.2. Crystalline Characterization.…”

“…According to the report by Li and co-workers, a sharp endothermic peak was exhibited at 398.15 K, which may be related to the crystalline transformation to the amorphous phase. However, from the results of DSC-TG and micro melting point instrument in this work, the temperature around 399.35 K should be the melting point of pramipexole, which is close to 402.15 K reported by Pu and co-workers …”

“…The solubility data of pramipexole in some pure solvents were experimentally determined by Pu and co-workers . As shown in Figure , the solubility data were compared with the data from ref .…”

“…The solubility data of pramipexole in some pure solvents were experimentally determined by Pu and co-workers. 30 As shown in Figure 4, the solubility data were compared with the data from ref 30. The absolute values of maximum and minimum relative deviation between the experimental solubility of pramipexole and that reported by Pu and co-workers were 78.8 and 13.1%, respectively, and the absolute value of the maximum relative deviation was obtained in 2-propanol, Through systematic repeated experiments in this work, it was found that the solubility of pramipexole in ethanol should be greater than that in 2-propanol.…”

Development of Pramipexole Prolonged-Release Matrix Tablets

“…Absolútna biologická dostupnosť je viac ako 90 %, maximálne plazmatické koncentrácie sa objavia približne 6 hodín po podaní tabliet a pramipexol sa vylučuje v nezmenenej forme renálnou cestou. Dobrá rozpustnosť pramipexolu dihydrochloridu monohydrátu vo vode si vyžaduje starostlivý výber polymérov riadiacich uvoľňovanie liečiva z matricových formulácií 3 .…”