الفهرس 
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Abstract
The Purpose Of The Current Study Was To Develop Nanotransfersomes-Loaded Thermosensitive In Situ Gel For Rectal Administration Of Tizanidine Hcl (TIZ), Aiming To Bypass The Hepatic First Pass Metabolism With Improved Bioavailability And Sustained Release Of The Drug. TIZ- Loaded Transfersomes Were Prepared By Thin-Film Hydration Method Followed By characterization Of The Prepared Vesicles For Various Parameters Such As Entrapment Efficiency, Particle Size, In Vitro Release Study And Ex Vivo Permeation Study. TIZ-Loaded Transfersomal Formula Composed Of Phosphatidylcholine And Tween 80 At A Weight Ratio Of (85:15) Gave Satisfactory Results. It Exhibited Encapsulation Efficiency Of 52.39 %, Particle Size Of 150.33 Nm, Controlled TIZ Release Over 8 H And Good Permeation characteristics. It Was Then Incorporated Into Pluronic Based Thermo-Reversible In Situ Gel Using HPMC As A Mucoadhesive Polymer. In Situ Gel Was Further characterized In Term Of Physical Parameters, In Vitro Drug Release, Ex Vivo Permeation Study, In Vivo Localization And Histopathological Evaluation. Finally, Pharmacokinetic Study Of Transfersomes-Loaded In Situ Gel Was Performed After Its Rectal Administration To Rabbits And Compared With Rectal TIZ In Situ Gel And Oral Drug Solution. The Study Revealed That The Formulation Successively Enhanced The Bioavailability Of TIZ By About 2.2 Fold And Increased The Half-Life Of The Drug To About 10 H. It Can Be Concluded That The Incorporation Of Nanotransfersomes Into Gel Vehicle Can Achieve A Dual Purpose Of Prolonged TIZ Release And Enhanced Bioavailability. Thus, Transfersomes-Loaded In Situ Gel Was Found To Be A Promising Drug Delivery System Of TIZ For The Treatment Of Spasticity.
Thus, The Work In This Thesis Is Divided Into Three Chapters:
Chapter I: Formulation And Evaluation Of Tizanidine Hcl–Loaded Nanotransfersomes.
Chapter II: Formulation And Evaluation Of Mucoadhesive Thermosensitive In Situ Gel Formulations.
Chapter III: Bioavailability Study Of Tizanidine Hcl from selected Formulations.