Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
Drug Dev Ind Pharm. 2009 Dec;35(12):1487-95. doi: 10.3109/03639040903025863.
Active pharmaceutical ingredient agglomerates can generate many solid product regulatory compliance issues.
To study the effects of shear rate, strain, type of excipient, and grade of acetaminophen (APAP) on the process of APAP de-agglomeration.
A shear-controlled environment is used to expose six different blends that consist of one of three APAP grades and one of two possible types of excipient to 10 different combinations of shear rate and strain. APAP agglomerates are sifted and weighed.
Finer APAP grades lead to blends with more APAP agglomerates and type of excipient only affects the de-agglomeration process for the finest APAP grade. De-agglomeration proceeds mainly as a function of strain with a minor contribution toward further de-agglomeration when larger shear rates are used.
When mechanical stress (which us proportional to shear rate) overcomes interparticle forces, de-agglomeration occurs. Higher shear rates (and stress) contribute slightly to further APAP de-agglomeration. Extended exposure to stress (strain) reduces the size and the number of agglomerates. Blends with finer APAP present more agglomerates, particularly after low strain exposure.
This article presents a useful method for formulation and process development. Exposing blends to higher shear rates and especially to strain mitigates APAP agglomeration in blends. Finer APAP presents more agglomerates and the type of excipient used affects the degree of APAP agglomeration.
活性药物成分团聚体可能会引发许多固体产品合规性问题。
研究剪切速率、应变、赋形剂类型和对乙酰氨基酚（APAP）等级对 APAP 解团聚过程的影响。
使用剪切控制环境，将六种不同的混合物暴露于 10 种不同的剪切速率和应变组合中，这些混合物由三种 APAP 等级中的一种和两种可能的赋形剂类型中的一种组成。APAP 团聚体被筛选和称重。
较细的 APAP 等级导致混合物中 APAP 团聚体更多，赋形剂类型仅对最细的 APAP 等级的解团聚过程有影响。解团聚主要作为应变的函数进行，当使用较大的剪切速率时，对进一步解团聚的贡献较小。
当机械应力（与剪切速率成正比）克服颗粒间的力时，就会发生解团聚。较高的剪切速率（和应力）对进一步的 APAP 解团聚有轻微贡献。延长暴露于应力（应变）会减小团聚体的大小和数量。含有较细 APAP 的混合物呈现出更多的团聚体，尤其是在低应变暴露后。
本文提出了一种用于配方和工艺开发的有用方法。将混合物暴露于较高的剪切速率，特别是应变，可以减轻混合物中的 APAP 团聚。较细的 APAP 呈现出更多的团聚体，并且所使用的赋形剂类型会影响 APAP 团聚的程度。
