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使用毛细管流变仪测定鼻喷雾剂悬浮液的剪切和拉伸流动行为。

The use of a capillary rheometer to determine the shear and extensional flow behaviour of nasal spray suspensions.

作者信息

Eccleston G M, Hudson N E

机构信息

Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow, UK.

出版信息

J Pharm Pharmacol. 2000 Oct;52(10):1223-32. doi: 10.1211/0022357001777351.

Abstract

The rheological profiles of four commercial nasal spray suspensions (Beconase, Flixonase, Nasacort and Nasonex) were compared using rotational viscometry. Two of the nasal sprays (Beconase and Nasonex) were further examined in both shear and extension using a capillary rheometer under conditions similar to those experienced at the spray nozzle (i.e. extremely high shear rates with significant stretching or extensional flow). In rotation, the shear viscosity fell rapidly with increase in shear rate. Plots of the viscosity derived at the lower shear rates in rotation were extrapolated to include the high-shear rate capillary values. At very high shear rates, the shear viscosity of Beconase was higher than that of Nasonex with the cross-over occurring in the extrapolated region at approximately 10,000 s(-1). In the transition region between laminar and turbulent flow (shear rate 6-8 x 10(4) s(-1)) there was a minimum in the shear viscosity to less than that of water for Nasonex and similar to water for Beconase, and a plateau region in extensional viscosity for Beconase but not Nasonex. These anomalies were due to the extensive aeration of both samples when sprayed. Whereas Beconase had de-aerated within 30 min of the experiment, Nasonex had not de-aerated completely after six weeks. The very low viscosity at the shear rates at the nozzle imply that it is unlikely that the low viscosity of the spray on delivery to the nose is a key factor in prolonging its residence time. The extensional viscosity for these rather fluid samples was over 1000-times the shear viscosity (not 3-times as with Newtonian fluids) and both sprays exhibited strain hardening over the range covered. The high extensional stress in the nozzle enables the fluid to form as reasonably sized droplets rather than fine atomized droplets, which rather than settling in the nose, would be prone to redistribution through the normal respiratory function. Both sprays resisted degradation despite the high shear rates and extensional stresses experienced.

摘要

使用旋转粘度测定法比较了四种市售鼻腔喷雾混悬液(伯克纳、辅舒良、内舒拿和雷诺考特)的流变学特性。其中两种鼻腔喷雾(伯克纳和雷诺考特)在类似于喷嘴处的条件下(即极高剪切速率且伴有显著拉伸或拉伸流动),使用毛细管流变仪在剪切和拉伸条件下进行了进一步研究。在旋转过程中,剪切粘度随剪切速率的增加而迅速下降。将旋转时较低剪切速率下得出的粘度曲线外推,以纳入高剪切速率毛细管值。在非常高的剪切速率下,伯克纳的剪切粘度高于雷诺考特,交叉点出现在外推区域内约10000 s⁻¹处。在层流和湍流的过渡区域(剪切速率为6 - 8×10⁴ s⁻¹),雷诺考特的剪切粘度有一个最小值,低于水的粘度,而伯克纳的剪切粘度与水相似,并且伯克纳在拉伸粘度方面有一个平稳区域,雷诺考特则没有。这些异常现象是由于两种样品在喷雾时都有大量曝气。尽管在实验30分钟内伯克纳已脱气,但六周后雷诺考特仍未完全脱气。在喷嘴处的剪切速率下粘度极低,这意味着喷雾在输送到鼻腔时的低粘度不太可能是延长其停留时间的关键因素。对于这些相当易流动的样品,拉伸粘度是剪切粘度的1000多倍(不像牛顿流体那样是3倍),并且两种喷雾在覆盖范围内都表现出应变硬化。喷嘴处的高拉伸应力使流体能够形成尺寸合理的液滴,而不是细雾化的液滴,细雾化液滴不会沉淀在鼻腔中,而是会通过正常呼吸功能易于重新分布。尽管经历了高剪切速率和拉伸应力,但两种喷雾都能抵抗降解。

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