帕洛诺司琼贴片的体外透过性能及在大鼠体内的药动学

制备了帕洛诺司琼透皮贴片并考察其体外释放和透过行为,以及在大鼠体内的药动学特征。分别采用3种不同类型的含羟基丙烯酸压敏胶(PSA-1、PSA-2和PSA-3)制备出F1、F2、F3贴片,通过影响因素试验、体外释放和体外透皮试验进行评价,筛选出优化贴片进行大鼠药动学试验。结果表明,处方F2中帕洛诺司琼的有关物质含量明显低于处方F1和F3,且帕洛诺司琼具有较快的释放速率及较高的体外透过能力,48 h累积透过率达到(78.8±11.6)%。F2贴片的大鼠药动学试验结果表明,贴片组比市售注射组有更长的消除半衰期(26.4±6.8)h vs.(16.4±5.9)h],绝对生物利用度为(33.1±13.2)%。因此,PSA-2制备的帕洛诺司琼透皮贴片经皮给药的可行性较高。

In vitro Permeation Evaluation and Pharmacokinetics in Rats of Palonosetron Patches

The palonosetron patches with different types of hydroxyl group-containing acrylic pressure sensitive adhesives(PSA-1, PSA-2 and PSA-3) were prepared, and the effects of PSA type on stability, in vitro release, and in vitro permeation profiles were also investigated to optimize the formulation. The prepared three types of patches called F1, F2 and F3 were respectively stored under high temperature, high humidity and high irradiation conditions for 10 d. The results showed that one related substance(called impurity 1) in formulation F2 was much lower than that in formulations F1 and F3. The results of in vitro release and in vitro permeation experiments showed that formulation F2 had faster release rate and better permeability compared with formulations F1 and F3. The cumulative permeation percentage of palonosetron from formulation F2 at 48 h reached as high as(78.8±11.6)%. So, the pharmacokinetics of formulation F2 in rats was investigated with the commercial injection as the control. The results showed that the elimination half-life of palonosetron in F2 patches group was longer than that in the injection group (26.4±6.8)h vs.(16.4±5.9)h], and the absolute bioavailability of F2 patches was(33.1±13.2)%. It was concluded that the palonosetron patches prepared with PSA-2 processed the feasibility of transdermal delivery.