H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Faculty of Pharmacy, Superior University, 6km Raiwind Road, Lahore, Pakistan.
Chem Phys Lipids. 2021 Mar;235:105052. doi: 10.1016/j.chemphyslip.2021.105052. Epub 2021 Jan 19.
Current study was aimed to design and develop muco-adhesive self-nano emulsifying drug delivery system (SNEDDs) for improved pharmacokinetics of Cefixime (CFX) in rabbits. The components of SNEDDs formulation i.e., cinnamon oil, Tween® 80, and PEG 200 as oil, surfactant, and co-surfactant respectively were selected based on their high solubilizing capability of the drug. SNEDDs formulation was optimized using Design of experiments (D-optimal design) in terms of droplet size, poly dispersity index and zeta potential. The optimized SNEDDs formulation was studied for various parameters like droplet size, morphology, zeta potential, emulsification, optical clarity, thermodynamic stability, GIT stability, and robustness to dilution. CFX was loaded to optimized formulation to form CFX-SNEDDs. Furthermore, acyl-chitosan, a muco-adhesive agent, was added to CFX-SNEDDS to prepare CHT-CFX-SNEDDS. In vitro drug release showed the controlled release behavior reached a maximum value of 70 % at pH 6.8 within 24 h. The droplet size, atomic force microscopy, and optical clarity analysis revealed the formation of nanosized emulsion (156 ± 25 nm) with spherical morphology. Also in vivo pharmacokinetic studies on rabbits showed an increased drug plasma concentration for CHT-CFX-SNEDDs (15 ± 3 μg/mL) and CFX-SNEDDs (9 ± 2 μg/mL) in comparison with control CFX (4 ± 1 μg/mL). The results indicated that the developed CHT-CFX-SNEDDs with an increased degree of solubilization, permeation, and nanosized range emulsion enhance the oral performance of CFX.
本研究旨在设计和开发一种具有黏膜黏附性的自微乳纳米给药系统（SNEDDS），以改善头孢克肟（CFX）在兔体内的药代动力学。根据药物的高溶解能力，选择 SNEDDS 制剂的成分，即肉桂油、吐温® 80 和聚乙二醇 200 分别作为油相、表面活性剂和助表面活性剂。根据粒径、多分散指数和zeta 电位，采用实验设计（D-最优设计）优化 SNEDDS 制剂。优化后的 SNEDDS 制剂进行了各种参数的研究，如粒径、形态、zeta 电位、乳化、光学透明度、热力学稳定性、胃肠道稳定性和对稀释的稳健性。将 CFX 载入优化后的制剂中形成 CFX-SNEDDS。此外，将具有黏膜黏附性的酰化壳聚糖添加到 CFX-SNEDDS 中，制备 CHT-CFX-SNEDDS。体外药物释放结果表明，在 pH 6.8 下 24 小时内达到最大释放度 70%，呈现控释行为。粒径、原子力显微镜和光学透明度分析表明，形成了纳米级乳液（156±25nm），形态呈球形。体内兔药代动力学研究也表明，与 CFX 对照组（4±1μg/mL）相比，CHT-CFX-SNEDDS（15±3μg/mL）和 CFX-SNEDDS（9±2μg/mL）的药物血浆浓度增加。结果表明，具有高增溶度、渗透性和纳米级乳液的开发的 CHT-CFX-SNEDDS 增强了 CFX 的口服性能。
