Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties
Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties
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DOI：
10.1007/s11095-015-1837-5
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发表时间：
2016-04-01
影响因子：
3.7
通讯作者：
Longest, P. Worth
中科院分区：
文献类型：
--
作者：
Rygg, Alex;Hindle, Michael;Longest, P. Worth
本研究的目的是使用最近开发的鼻腔溶出、吸收和清除（DAC）模型来评估悬浮药物颗粒大小对喷雾产品鼻上皮药物吸收的影响程度。利用计算流体动力学（CFD）模拟纤毛粘膜清除和药物溶出度，计算鼻腔喷雾泵给药的总上皮吸收和微尺度上皮吸收。评估了悬浮颗粒大小、药物溶解度和分配系数的范围。以糠酸莫米松为例，1-5 μ m范围内的悬浮药物颗粒大小不影响鼻上皮的总摄取。然而，低溶解度悬浮药物颗粒的微尺度吸收受颗粒大小的影响，这控制了药物渗透到鼻远端区域的程度。鼻- dac模型被证明是一个有用的工具，在确定鼻腔暴露的喷雾配方与不同的药物颗粒大小和溶解度。此外，该模型说明了一种局部鼻腔给药的新策略，其中选择药物颗粒大小以增加粘膜纤毛清除上皮表面暴露区域，同时最大限度地减少离开鼻咽的药物剂量。
The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product.Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated.Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 mu m did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions.The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.