Pharmaceutica Analytica Acta

Chitosan lactate wafer as a platform for the buccal delivery of Tizanidine HCl: In vitro and in vivo performance

4^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

March 24-26, 2014 Hilton San Antonio Airport, San Antonio, USA

Galal M El Mahrouk, Omaima N El Gazayerly, Ahmed A Aboelwafan and Maie S Taha

Accepted Abstracts: Pharmaceut Anal Acta

Abstract:

Tizanidine HCl is a skeletal muscle relaxant that suffers from extensive hepatic metabolism resulting in 34 to 40% oral bioavailability. It also suffers from short half-life (2.1-4.2 hrs) that necessitates frequent administration thus reducing patient compliance. In addition, Tizanidine HCl is water soluble, so it is a challenging candidate for controlled drug delivery. In our study, Tizanidine was encapsulated in chitosan lactate beads cross-linked with sodium tripolyphosphate. The beads were further incorporated into chitosan lactate wafer to be easily applied to buccal mucosa, aiming to bypass the hepatic metabolism. A Central Composite Face-centered Design was applied to statistically optimize the formulation variables; tripolyphosphate concentration, chitosan lactate concentration and polymer/drug ratio. The optimized formula suggested by the software composed of; 3.03% tripolyphosphate, 4.92% chitosan lactate and 2.13 polymer/drug ratio. It provided encapsulation efficiency of 56.5% and controlled Tizanidine release over 8 hours. It is also characterized by being mucoadhesive and nonirritant. Pharmacokinetic parameters of Tizanidine from the optimized formula were compared to those of the immediate release tablet, Sirdalud?, as reference in human volunteers using a randomized crossover design. Significant increase was observed for Tmax and AUC(0-∞). The increase in relative bioavailability of TIZ from the optimized formula was 2.27 fold.