الفهرس 
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Abstract
Terbutaline Sulfate (TBN), Β2-Adrenergic Receptor Agonist, Demonstrates Valuable Results In The Management Of Asthma; However, The Hepatic First-Pass Metabolism Associated With The Oral Administration Minimizes Its Clinical Performance. The Objective Of The Present Work Was To Formulate, Optimize And Evaluate TBN-Loaded Bilosomes (BLS) In Hydrogel For Transdermal Application And Also To Develop A Novel Non-Phospholipid Nanovesicular System Termed Novasomes (NVS) As An Elegant Drug Carrier For Effective Pulmonary Targeting Via Intratraceal (I.T) Instillation, Aiming At Evading The Hepatic First-Pass Metabolism Of TBN. Two Different Designs Were Anticipated To Statistically Optimize The Formulation Variables where Artificial Neural Network Modeling Was Employed For TBN-BLS Formulation, While Box-Behnken Design, Using Design-Expert® Was Used For TBN-NVS Formulation. Both TBN-BLS And TBN-NVS Were Prepared By Thin Film Hydration Technique. After Being Subjected To Physicochemical characterization, Optimized Formulations Were Enrolled In A Histopathological Study And Pharmacokinetic Investigation In A Rat Model. The Optimized TBN Chitosan Coated Bilosomes (TBN-CTS-BLS) Were Nano-Scaled Spherical Vesicles (245.13 ± 10.23 Nm) Having Reasonable Entrapment Efficiency (65.25 ± 5.51%) And Adequate Permeation characteristics Across The Skin (340.11 ± 22.34 µg/Cm2). The TBN-CTS-BLS Hydrogel Formulation Exhibited Better Permeation Parameters Than Free TBN Hydrogel And It Was Well-Tolerated With No Inflammatory Signs Manifested Upon Histopathological Evaluation. The Pharmacokinetic Study Revealed That The Optimized TBN-CTS-BLS Formulation Successively Enhanced The Bioavailability Of TBN By About 2.33-Fold And Increased T1/2 To About 6.30 ± 0.24 H As Compared To The Oral Solution. These Findings Support The Prospect Use Of BLS As Active And Safe Transdermal Carrier For TBN In The Treatment Of Asthma. On The Other Side, The Optimized TBN-NVS Formulation Has Showed EE% Of 67.48 ± 5.23%, Average Nano-Size Of 240.66 ± 22.41 Nm And Sustained Drug Release Up To 8 H. Moreover, It Has Showed Significant In Vitro Lung Deposition Pattern In Cascade Impactor With Fine Particle Fraction Of 62.50 ± 0.05% And The In Vivo Histopathological Studies Confirmed Safety Of I.T Administration Of The TBN-NVS. The Pharmacokinetic Study Disclosed Ameliorated Bioavailability Of The Optimum TBN-NVS By 3.88-Fold As Compared To The Oral TBN Solution. Concisely, The Foregoing Results Recommended The TBN-NVS As A Promising Platform For TBN In The Pulmonary Delivery For Integral Curbing Of The Disease Due To Target Specificity.
Keywords: Terbutaline Sulfate; Transdermal; Bilosomes; Artificial Neural Network; Pulmonary Targeting; Novasomes; Box-Behnken Design; Pharmacokinetic Studies.