测量水基药物悬浮液时稀释的危险以及Nanoflex如何克服这些障碍

D. Pugh
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摘要

50年来,动态光散射(DLS)技术一直是测定细颗粒悬浮液、微乳剂和纳米级物质中粒径分布的重要工具。许多纳米材料是在非水介质中测量的,只要我们知道这些介质在两种不同温度下的粘度,那么分析就相对简单了。然而,大多数药物悬浮液是水基的,关键的危险不在于采样,而在于化学。当测量颗粒的大小时,事先研究它们的zeta电位是非常重要的,因为高zeta电位表示稳定的产物,而低zeta电位表示不稳定的产物可能聚集。当两个粒子有很高的ζ电位时,它们会像两个负极或正极磁铁一样相互排斥,所以它们不会相互吸引,从而导致稳定的溶液。当样品被稀释时,其zeta电位会发生剧烈变化,特别是当稀释导致zeta电位接近等电点(IEP-0 m伏)时。有许多影响可能导致zeta电位在稀释后降低到0 mV;我们将涵盖pH值,盐浓度和聚电解质或表面活性剂浓度。遇到这个问题有两种方法,第一种方法需要充分了解悬浮液的pH值、盐浓度和表面活性剂的体积%浓度,这样才能进行稀释(预防)。第二个涉及技术进步(预防和治疗),这是独特的,并采用了一种在大多数制药应用中无需稀释的方法。通过在全浓度下测量悬浮液,消除了所有潜在的化学问题。
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The Dangers of Dilution When Measuring Water Based Pharmaceutical Suspensions and How Nanoflex Overcomes these Obstacles
Dynamic Light Scattering (DLS) has been an important tool for determining particle size distributions in fine particulate material suspensions, micro emulsions and Nano-scale matter in general for 50 years. Many Nano scale materials are measured in non-aqueous media and as long as we know the viscosities in these media at 2 different temperatures, then the analysis are relatively simple. However most pharmaceutical suspensions are water based and the key danger is not in the sampling but the chemistry. When measuring the size of particles, a study of their zeta potential in advance is extremely important as a high zeta potential is indicative of a stable product whilst a low zeta potential is indicative of an unstable product likely to agglomerate. When two particles have a high zeta potential they repel each other like 2 negative or positive magnets so they are not attracted to each other thus leading to a stable solution. When a sample is diluted dramatic changes to its zeta potential can occur especially when the dilution causes the zeta potential to approach the Iso Electric Point (IEP-0 m Volts). There are a number of effects which may cause the zeta potential to decrease towards 0 mV after dilution; we will cover pH, salt concentration and polyelectrolyte or surfactant concentration. There are 2 approaches to take when encountering this problem, The first approach requires full knowledge of the suspensions pH, salt concentration and volume % concentration of the surfactant such that care in dilution may be effected (Prevention). The second involves technological advances (Prevention and Cure) which are unique and employs a method which in most pharmaceutical applications renders the need to dilute redundant. By measuring the suspension at full concentration, all potential chemistry problems are negated.
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