From the Department of Pediatrics, Division of Allergy and Immunology, University of California, San Diego, School of Medicine California.
ENT Department, Ghent University Hospital, Ghent, Belgium.
Allergy Asthma Proc. 2020 Jul 1;41(4):265-270. doi: 10.2500/aap.2020.41.200028. Epub 2020 May 11.
Intranasal antihistamines and steroids should be delivered in a volume and with a technique that allow for optimal drug retention within the entire nasal cavity, maximize local absorption by the nasal mucosa, and, subsequently, increase the potential for the most desirable local availability and therapeutic effect. This in vitro evaluation simulated nasal medication deposition and evaluated the extent of runoff. MP-AzeFlu, a novel intranasal formulation of azelastine hydrochloride (AZE) plus fluticasone propionate (FP), was compared with sequential sprays of available commercial products with the individual medication components. A model of a normal adult human nasal cavity was used to visualize deposition of nasal spray products. A single spray of MP-AzeFlu (0.137 mL [137 μg of AZE/50 μg of FP]) or single sequential sprays of AZE nasal spray (0.137 mL [137 μg]) followed by brand name or generic FP nasal spray (0.100 mL [50 μg]) were manually actuated into the model. The interior was coated with a water-sensitive dye that changes to magenta when exposed to aqueous-based formulations. A slight vacuum was applied during spray delivery to simulate sniffing. The results were photographed by using anterior and lateral views. Three replicates of MP-AzeFlu showed no dripping from the front of the nostril or backflow from the nasal cavity. However, three replicates of AZE nasal spray, followed by a brand name or generic FP nasal spray, showed significant dripping from the front of the nostril and backflow from the nasal cavity. A single spray of MP-AzeFlu resulted in no runoff compared with sequential dosing of the two other therapeutic products. Product runoff is likely due to the volume exceeding the capacity of the nasal cavity model. Furthermore, the common clinical dosing regimen of two sprays per nostril of each of the individual components would promote even greater increased undesirable flooding and leakage.
鼻腔抗组胺药和类固醇应该以一种能够使药物在整个鼻腔内得到最佳保留、最大限度地通过鼻腔黏膜吸收、从而增加最理想的局部可用性和治疗效果的体积和技术来输送。这项体外评估模拟了鼻腔药物沉积，并评估了流失程度。MP-AzeFlu 是一种新型盐酸氮䓬斯汀（AZE）加丙酸氟替卡松（FP）的鼻腔制剂，与现有商业产品的顺序喷雾以及单独药物成分进行了比较。使用正常成人鼻腔模型来可视化鼻腔喷雾产品的沉积。手动将 MP-AzeFlu（0.137 毫升[137μg 的 AZE/50μg 的 FP]）或 AZE 鼻腔喷雾（0.137 毫升[137μg]）的单个顺序喷雾，然后是品牌名称或通用 FP 鼻腔喷雾（0.100 毫升[50μg]），单次喷雾到模型中。内部涂有水敏性染料，当暴露于水基制剂时，该染料会变成洋红色。在喷雾输送过程中施加轻微的真空，以模拟嗅探。使用前视图和侧视图拍摄结果。MP-AzeFlu 的三个重复样本均未从鼻孔前端滴落或从鼻腔回流。然而，AZE 鼻腔喷雾的三个重复样本，然后是品牌名称或通用 FP 鼻腔喷雾，显示出明显从前鼻孔滴落和从鼻腔回流。与其他两种治疗产品的顺序给药相比，MP-AzeFlu 的单次喷雾没有流失。产品流失可能是由于体积超过鼻腔模型的容量。此外，每个单独成分每侧鼻孔两次喷雾的常见临床给药方案会促进甚至更大的不必要的泛滥和泄漏。
