Purpose

Tizanidine (TZN) is used for the management of muscle spasms. Oral TZN is liable to first-pass metabolism and interindividual variation. Transdermal drug delivery systems (TDDS) are gaining research attention as an alternative route. The aim of this study is the bioanalytical comparison of the oral route and two TDDS, bilosomes and aspasomes.

Methods

TZN-loaded bilosomes and aspasomes were applied to mice. The plasma concentration of TZN was determined in mice plasma post application by in-house developed HPLC method. Results were compared to those obtained post an equal oral dose. Pharmacokinetic parameters were deduced and statistically compared.

Results

The TDDS route significantly enhanced the bioavailability and plasma concentration of TZN (p < 0.0009; CL = 95). The drug half-life (t_1/2) significantly increased (< 0.0001; CL = 95) when using the TDDS instead of the oral route. Among the TDDS vesicles, the bilosomes significantly enhance bioavailability and C_max over aspasomes (p < 0.0316; CL = 95). Both vesicles were not statistically different in terms of extending the drug half-life.

Conclusions

In conclusion, the bioanalytical comparison revealed that the TDDS can overcome the first-pass effect of TZN and enhances its bioavailability over the oral route. Bilosomes were more efficient than aspasomes for enhancing the TZN bioavailability. Both vesicular formulas were equivalent for extending the half-life of the drug.

中文翻译：

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从不同的纳米囊泡载体透皮递送替扎尼定的生物分析比较。

目的

替扎尼定（TZN）用于管理肌肉痉挛。口服TZN易于首过代谢和个体差异。透皮给药系统（TDDS）作为替代途径正在引起研究关注。这项研究的目的是对口服途径与两种TDDS（胆汁小体和天冬氨酸小体）进行生物分析比较。

方法

将负载TZN的胆小体和天冬氨酸应用于小鼠。通过内部开发的HPLC方法测定小鼠血浆中TZN的浓度。将结果与等剂量口服后获得的结果进行比较。推导出药代动力学参数并进行统计比较。

结果

TDDS途径显着提高了TZN的生物利用度和血浆浓度（p  <0.0009； CL = 95）。使用TDDS代替口服途径时，药物半衰期（t _1/2）显着增加（<0.0001; CL = 95）。间的TDDS囊泡，所述胆汁盐体显著提高生物利用度和C_最大值超过aspasomes（p  <0.0316; CL = 95）。就延长药物半衰期而言，两个囊泡在统计学上均无差异。

结论

总之，生物分析比较表明，TDDS可以克服TZN的首过效应，并提高其口服途径的生物利用度。在增强TZN的生物利用度方面，比Gaspsomes更有效。两种囊泡配方均等效于延长药物的半衰期。