Islam Nayyer, Irfan Muhammad, Zahoor Ameer Fawad, Iqbal Muhammad Shahid, Syed Haroon Khalid, Khan Ikram Ullah, Rasul Akhtar, Khan Salah-Ud-Din, Alqahtani Alaa M, Ikram Muzzamil, Abdul Qayyum Muhammad, Khames Ahmed, Inam Sana, Abourehab Mohammed A S
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan.
Department of Chemistry, Government College University, Faisalabad 38000, Pakistan.
Pharmaceutics. 2021 Aug 23;13(8):1315. doi: 10.3390/pharmaceutics13081315.
The main objective of this research work was the development and evaluation of transfersomes integrated oral films for the bioavailability enhancement of Ebastine (EBT) to treat allergic rhinitis. The flexible transfersomes, consisting of drug (EBT), lipid (Phosphatidylcholine) and edge activator (EA) Polyoxyethylene sorbitan monooleate or Sorbitan monolaurate, were prepared with the conventional thin film hydration method. The developed transfersomes were further integrated into oral films using the solvent casting method. Transfersomes were evaluated for their size distribution, surface charge, entrapment efficiency (EE%) and relative deformability, whereas the formulated oral films were characterized for weight, thickness, pH, folding endurance, tensile strength, % of elongation, degree of crystallinity, water content, content uniformity, in vitro drug release and ex vivo permeation, as well as in vivo pharmacokinetic and pharmacodynamics profile. The mean hydrodynamic diameter of transfersomes was detected to be 75.87 ± 0.55 nm with an average PDI and zeta potential of 0.089 ± 0.01 and 33.5 ± 0.39 mV, respectively. The highest deformability of transfersomes of 18.52 mg/s was observed in the VS-3 formulation. The average entrapment efficiency of the transfersomes was about 95.15 ± 1.4%. Transfersomal oral films were found smooth with an average weight, thickness and tensile strength of 174.72 ± 2.3 mg, 0.313 ± 0.03 mm and 36.4 ± 1.1 MPa, respectively. The folding endurance, pH and elongation were found 132 ± 1, 6.8 ± 0.2 and 10.03 ± 0.4%, respectively. The ex vivo permeability of EBT from formulation ETF-5 was found to be approximately 2.86 folds higher than the pure drug and 1.81 folds higher than plain film (i.e., without loaded transfersomes). The relative oral bioavailability of ETF-5 was 2.95- and 1.7-fold higher than that of EBT-suspension and plain film, respectively. In addition, ETF-5 suppressed the wheal and flare completely within 24 h. Based on the physicochemical considerations, as well as in vitro and in vivo characterizations, it is concluded that the highly flexible transfersomal oral films (TOFs) effectively improved the bioavailability and antihistamine activity of EBT.
本研究工作的主要目的是开发和评估用于提高依巴斯汀（EBT）生物利用度以治疗过敏性鼻炎的传递体包载口腔膜剂。采用传统的薄膜水化法制备了由药物（EBT）、脂质（磷脂酰胆碱）和边缘活化剂（EA）聚氧乙烯山梨醇酐单油酸酯或脱水山梨醇单月桂酸酯组成的柔性传递体。采用溶剂浇铸法将制备的传递体进一步整合到口腔膜剂中。对传递体的粒径分布、表面电荷、包封率（EE%）和相对变形性进行了评估，而对制备的口腔膜剂进行了重量、厚度、pH值、耐折度、拉伸强度、伸长率、结晶度、含水量、含量均匀度、体外药物释放和离体渗透以及体内药代动力学和药效学特征的表征。测得传递体平均流体动力学直径为75.87±0.55nm，平均多分散指数（PDI）和zeta电位分别为0.089±0.01和33.5±0.39mV。在VS-3制剂中观察到传递体的最高变形性为18.52mg/s。传递体的平均包封率约为95.15±1.4%。发现传递体包载口腔膜剂表面光滑，平均重量、厚度和拉伸强度分别为174.72±2.3mg、0.313±0.03mm和36.4±1.1MPa。耐折度、pH值和伸长率分别为132±1、6.8±0.2和10.03±0.4%。发现EBT从制剂ETF-5的离体渗透率比纯药物高约2.86倍，比空白膜（即未载传递体的膜）高1.81倍。ETF-5的相对口服生物利用度分别比EBT混悬液和空白膜高2.95倍和1.7倍。此外，ETF-5在24小时内完全抑制了风团和潮红。基于物理化学因素以及体外和体内表征，得出结论：高度柔性的传递体包载口腔膜剂（TOFs）有效地提高了EBT的生物利用度和抗组胺活性。
