New generation of amphiphilic vesicles known as aspasomes were investigated as potential carriers for transdermal delivery of tizanidine (TZN). Using full factorial design, an optimal formulation was developed by evaluating the effects of selected variables on the properties of the vesicles with regards to entrapment efficiency, vesicle size and cumulative percentage released. The optimal formula (TZN-AS 6) consisting of 20 mg TZN, 50 mg ascorbyl palmitate (AP), 50 mg cholesterol (CH) and 50 mg Span 60, represented well dispersed spherical vesicles in the nanorange sizes and exhibited excellent stability under different storage conditions. Ex-vivo permeation studies using excised rat skin showed a 4.4-fold increase of the steady state flux in comparison to the unformulated drug (p < 0.05). The pharmacokinetic parameters obtained from the in-vivo study using Wistar rats, showed that the bioavailability of TZN was enhanced significantly (p < 0.05) when compared to the oral market product of TZN, Sirdalud®. Moreover, skin irritancy tests confirmed that the vesicles were non-invasive and safe for the skin. Based on the results obtained, the optimised aspasomes formula represents a promising Nano platform for TZN to be administered transdermally, thus improving the therapeutic efficacy of this important muscle relaxant.
Keywords: Tizanidine hydrochloride; aspasomes; ex-vivo permeation; pharmacokinetics; stability studies.