title: Chitosan lactate wafer as a platform for the buccal delivery of tizanidine HCl: in vitro and in vivo performance.
abstract: Tizanidine HCl is a skeletal muscle relaxant that suffers from extensive hepatic metabolism resulting in 34-40% oral bioavailability. It also suffers from short half-life (2.1-4.2h) 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 8h. 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.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini street, Cairo 11562, Egypt.
authors.forename: Galal M
authors.initials: GM
authors.lastname: El-Mahrouk
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini street, Cairo 11562, Egypt.
authors.forename: Omaima N
authors.initials: ON
authors.lastname: El-Gazayerly
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini street, Cairo 11562, Egypt. Electronic address: aaboelwafa@hotmail.com.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Aboelwafa
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini street, Cairo 11562, Egypt.
authors.forename: Maie S
authors.initials: MS
authors.lastname: Taha
mesh_terms: D000268:Adhesiveness; D000278:Administration, Buccal; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry*; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D003432:Cross-Linking Reagents / Q000737:chemistry; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006207:Half-Life; D006801:Humans; D007773:Lactates / Q000737:chemistry*; D008297:Male; D008657:Metabolic Clearance Rate; D009465:Neuromuscular Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011122:Polyphosphates / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007773:Lactates; D009465:Neuromuscular Agents; D011122:Polyphosphates; D013607:Tablets; C023754:tizanidine; D048271:Chitosan; D003000:Clonidine; C005692:triphosphoric acid
keywords: Buccoadhesive; Central composite face-; Chitosan lactate; Na tripolyphosphate; Wafer containing; beads; centered design