Linking Suspension Nasal Spray Drug Deposition Patterns to Pharmacokinetic Profiles: A Proof-of-Concept Study Using Computational Fluid Dynamics.
Linking Suspension Nasal Spray Drug Deposition Patterns to Pharmacokinetic Profiles: A Proof-of-Concept Study Using Computational Fluid Dynamics.
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DOI：
10.1016/j.xphs.2016.03.033
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发表时间：
2016-06
影响因子：
3.8
通讯作者：
Longest PW
中科院分区：
文献类型：
--
作者：
Rygg A;Hindle M;Longest PW
本研究的目的是将用计算流体动力学（CFD）预测的混悬液制剂的局部鼻喷雾沉积模式与体内人体药代动力学（PK）血浆浓度曲线联系起来。这是通过使用CFD模拟结合房室PK建模来实现的。结果显示，由于沉积在鼻中通道中的药物颗粒的吸收，血浆浓度的初始快速升高，随后由于药物颗粒从鼻前庭转运至鼻中通道，血浆浓度升高较慢。尽管鼻腔中的药物沉积位置对浓度曲线的形状有显著影响，但如果所有药物在模拟过程中保留在鼻子中，则绝对生物利用度保持恒定。即使经过很长时间，药物通过鼻孔的损失也会导致生物利用度显著降低和变异性增加。本研究的结果量化了鼻腔药物沉积的差异如何影响瞬时血浆浓度和总体生物利用度。这些发现可能有助于建立鼻喷雾装置的生物等效性，并减轻体外试验、药效学和临床研究的负担。
The objective of this study is to link regional nasal spray deposition patterns of suspension formulations, predicted with computational fluid dynamics (CFD), to in vivo human pharmacokinetic (PK) plasma concentration profiles. This is accomplished through the use of CFD simulations coupled with compartmental PK modeling. Results showed a rapid initial rise in plasma concentration that is due to the absorption of drug particles deposited in the nasal middle passages, followed by a slower increase in plasma concentration that is governed by the transport of drug particles from the nasal vestibule to the middle passages. Although drug deposition locations in the nasal cavity had a significant effect on the shape of the concentration profile, the absolute bioavailability remained constant provided that all of the drug remained in the nose over the course of the simulation. Loss of drug through the nostrils even after long time periods resulted in a significant decrease in bioavailability and increased variability. The results of this study quantify how differences in nasal drug deposition affect transient plasma concentrations and overall bioavailability. These findings are potentially useful for establishing bioequivalence for nasal spray devices and reducing the burden of in vitro testing, pharmacodynamics and clinical studies.