University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Zagreb, Croatia.
University of Split, Faculty of Science, Department of Mathematics, Split, Croatia.
Int J Pharm. 2019 May 30;563:445-456. doi: 10.1016/j.ijpharm.2019.04.015. Epub 2019 Apr 6.
The aim of this study was to develop an innovative in situ gelling suspension for effective nasal delivery of fluticasone. Pectin, gellan gum and sodium hyaluronate were used as gelling/thickening agents, and Tween 80 as a suspending agent. The influence of the formulation and/or administration parameters on formulation sprayability and nasal deposition was explored with an appropriate experimental design with the range for parameters in the design obtained from previous research and domain knowledge. All formulations exhibited appropriate sprayability and instant gelation upon mixing with simulated nasal fluid exhibiting weak gel properties convenient for nasal delivery. Targeted turbinate deposition depended on administration and formulation parameters, including their interactions. Decrease in the administration angle from horizontal plane, increase in inspiratory flow and presence of sodium hyaluronate significantly increased deposition in turbinate region. Parameters in interactions included concentration of polymers, surfactant and fluticasone, as well as administration angle. Selected formulations with high turbinate deposition exhibited significant increase in viscosity upon gelation, showing potential to prolong the drug retention at the nasal mucosa. The highest effect on the gel viscosity, strength and fluticasone release profile was observed for gellan gum, thus recognised as crucial parameter for the optimisation of overall therapeutic effect.
本研究旨在开发一种创新的原位凝胶混悬剂,以实现氟替卡松的有效鼻腔递药。果胶、结冷胶和透明质酸钠被用作胶凝/增稠剂,吐温 80 用作混悬剂。通过适当的实验设计,探讨了制剂和/或给药参数对制剂喷雾性能和鼻腔沉积的影响,设计中的参数范围是从先前的研究和领域知识中获得的。所有制剂与模拟鼻腔液混合后均表现出适当的喷雾性能和即时胶凝,表现出便于鼻腔给药的弱凝胶特性。靶向鼻甲沉积取决于给药和制剂参数,包括它们的相互作用。从水平面降低给药角度、增加吸气流量和加入透明质酸钠均显著增加了鼻甲区域的沉积。相互作用中的参数包括聚合物、表面活性剂和氟替卡松的浓度,以及给药角度。具有高鼻甲沉积的选定制剂在胶凝时表现出显著增加的粘度,显示出在鼻黏膜处延长药物滞留时间的潜力。对凝胶粘度、强度和氟替卡松释放曲线的影响最大的是结冷胶,因此被认为是优化整体治疗效果的关键参数。