Bioanalytical Comparison of Transdermal Delivery of Tizanidine from Different Nanovesicular Carriers

Abstract

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. 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. The TDDS route significantly enhanced the bioavailability and plasma concentration of TZN (p < 0.0009; CL = 95). The drug half-life (t1/2) 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 Cmax over aspasomes (p < 0.0316; CL = 95). Both vesicles were not statistically different in terms of extending the drug half-life. 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.