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层流流通式溶出仪的设计与特性:与常见溶出技术的流体动力学条件比较。

Design and characterization of a laminar flow-through dissolution apparatus: Comparison of hydrodynamic conditions to those of common dissolution techniques.

机构信息

Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut, USA.

出版信息

Pharm Dev Technol. 2011 Feb;16(1):75-87. doi: 10.3109/10837450903499341. Epub 2010 Jan 27.

Abstract

A flow-through dissolution apparatus was designed and evaluated to screen small quantities of pharmaceutical drug compounds early in development. The apparatus was designed to mount on a microscope slide such that a compacted solid drug was positioned flush along one wall and the fluid flow in the apparatus was laminar flow in a rectangular duct. Stereomicroscopic digital images and Raman spectra of the solid were taken during dissolution and the effluent dissolution medium was collected in fractions to determine the dissolution rate by fluorescence or HPLC/UV. Three compounds, triamterene, ketoprofen, and β-naphthoic acid were investigated in the dissolution flow cell at various hydrodynamic conditions. In conditions where no solvent-mediated conversion was expected, there was a decrease in dissolution rate with time in the flow through cell that was associated with surface smoothing. This phenomenon also occurred in rotating disk experiments. In either case, the magnitude and time course of the decrease in dissolution rate with time is generally different enough to distinguish from the decrease in dissolution rate due to solvent-mediated conversion.

摘要

设计并评估了一种流通式溶出仪,以便在药物开发早期筛选小批量的药物化合物。该仪器设计为安装在显微镜载玻片上,使得压实的固体药物沿一个壁平齐放置,并且仪器中的流体流动为矩形管道中的层流。在溶出过程中拍摄了固体的立体显微镜数字图像和拉曼光谱,并将流出的溶出介质收集在不同的分数中,通过荧光或 HPLC/UV 测定溶出速率。在不同的流体动力学条件下,用溶出流动池研究了三种化合物,阿米洛利、酮洛芬和β-萘酸。在预计没有溶剂介导转化的情况下,在流通池中的溶解速率随时间的推移而降低,这与表面平滑有关。这种现象也发生在旋转圆盘实验中。在这两种情况下,溶解速率随时间的降低幅度和时间进程通常足以与溶剂介导转化引起的溶解速率降低区分开来。

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