Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada.
Pharmaceutical Technology & Development, AstraZeneca R&D, South San Francisco, CA, USA.
Int J Pharm. 2018 Sep 5;548(1):128-138. doi: 10.1016/j.ijpharm.2018.06.053. Epub 2018 Jun 26.
A new shadowgraphic imaging method and an associated instrument for analyzing the physical stability of pharmaceutical suspensions are introduced in this paper. The new suspension tester consists mainly of a high-resolution camera that takes sequential shadowgraphic images of emulsions or suspensions and a 2D collimated LED for simultaneous whole-sample illumination in bright field. A built-in ultrasonic bath provides controlled initial agitation to the samples of interest. Sequential images acquired by the experimental setup were used to derive normalized transmission profiles from which an instability index was developed for quantitative stability comparison between samples. Instrument performance was verified by measuring the stability of a series of oil-in-water emulsions prepared with surfactant mixtures of different ratios. The new instrument correctly determined the required hydrophilic-lipophilic balance for sunflower oil to be 7.0. The stability of a pressurized suspension of spray dried lipid (DSPC) particles was monitored for 5 days after propellant filling. Although stable for the first 24 h, the lipid suspension was found to decrease in stability from day 1 to day 4. Morphological and spectroscopic analysis revealed that the suspended DSPC particles had reformed into large thin sheets of lipid, thereby causing the gradual stability decrease during the aging study. The effects of initial agitation on the stability of suspensions were demonstrated by agitating a suspension of micronized fluticasone propionate in propellant using a wrist action shaker and an ultrasonic bath respectively. A significant improvement of suspension stability was achieved by replacing the wrist action shaker method with ultrasonic agitation. Simultaneous illumination of the complete suspension, a high image acquisition rate, and controlled initial agitation are features that make this new suspension tester a suitable and more reliable instrument for investigating the stability of pressurized pharmaceutical suspensions.
本文介绍了一种用于分析药物混悬剂物理稳定性的新阴影成像方法和相关仪器。新的混悬剂测试仪主要由一个高分辨率相机组成，该相机可对乳剂或混悬剂进行连续的阴影成像，以及一个二维准直 LED，用于对整个样品进行明场同步整体照明。内置的超声波浴为感兴趣的样品提供受控的初始搅拌。通过实验装置获取的连续图像用于从归一化传输曲线中得出不稳定指数，以便对样品之间的定量稳定性进行比较。通过测量用不同比例的表面活性剂混合物制备的一系列油包水乳液，验证了仪器的性能。该新仪器正确确定了葵花籽油所需的亲水亲油平衡值为 7.0。对喷雾干燥脂质（DSPC）颗粒加压混悬液在推进剂填充后的 5 天内进行了稳定性监测。尽管在最初的 24 小时内稳定，但在第 1 天至第 4 天发现脂质混悬液的稳定性逐渐降低。形态学和光谱分析表明，悬浮的 DSPC 颗粒已重新形成大的薄脂质片，从而导致在老化研究过程中稳定性逐渐降低。通过分别使用腕式动作摇床和超声波浴对推进剂中的微米化丙酸氟替卡松混悬液进行初始搅拌，证明了初始搅拌对混悬液稳定性的影响。通过用超声波搅拌代替腕式动作摇床方法，显著提高了混悬液的稳定性。对整个混悬液的同步照明、高图像采集率和受控的初始搅拌是使这种新的混悬剂测试仪成为研究加压药物混悬剂稳定性的合适且更可靠仪器的特点。
