A discriminatory intrinsic dissolution study using UV area imaging analysis to gain additional insights into the dissolution behaviour of active pharmaceutical ingredients
A discriminatory intrinsic dissolution study using UV area imaging analysis to gain additional insights into the dissolution behaviour of active pharmaceutical ingredients
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DOI：
10.1016/j.ijpharm.2012.05.023
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发表时间：
2012-09-15
影响因子：
5.8
通讯作者：
Forbes, Robert T.
中科院分区：
文献类型：
--
作者：
Hulse, Wendy L.;Gray, Jason;Forbes, Robert T.
为了高效和有效的药物开发，需要尽早深入了解潜在候选药物的溶出行为及其物理形式，并且当时可用的材料量有限。使用3-10 mg样品量，研究了UV成像系统的能力，以提供对流动条件下评估的一系列化合物和物理形式的固有溶出曲线的深入机理洞察。将物理形式的吲哚美辛、茶碱和布洛芬压缩，并且在压缩之前和之后用X射线方法和/或拉曼光谱法确认它们的固态形式。固有的溶解速率（IDR）确定使用紧凑的紫外成像配置文件。茶碱无水物与水合物的IDR比为2.1，吲哚美辛α型与γ型的IDR比约为1.7。新的UV区域可视化方法的区分能力被证明是高的，因为可以检测到微粉化后工艺诱导的固态溶出差异。此外，缩小系统能够可视化先前观察到的布洛芬IDR随十二烷基硫酸钠浓度增加而增加。来自可视化方法的机械溶解见解是显而易见的。(c)2012爱思唯尔有限公司版权所有。
For efficient and effective drug development it is desirable to acquire a deep understanding of the dissolution behaviour of potential candidate drugs and their physical forms as early as possible and with the limited amounts of material that are available at that time. Using 3-10 mg sample quantities, the ability of a UV imaging system is investigated to provide deep mechanistic insight into the intrinsic dissolution profiling of a range of compounds and physical forms assessed under flow conditions. Physical forms of indomethacin, theophylline and ibuprofen were compressed and their solid-state form confirmed before and after compression with X-ray methods and/or Raman spectroscopy. Intrinsic dissolution rates (IDRs) were determined using the compact's UV-imaging profile. The ratio in the IDRs for theophylline anhydrate over hydrate was 2.1 and the ratio for the alpha form of indomethacin over the gamma form was approximately 1.7. The discriminatory power of the novel UV area visualisation approach was shown to be high in that process-induced solid-state dissolution differences post-micronisation could be detected. Additionally, the scale-down system was able to visualise a previously observed increase in ibuprofen IDR with an increase in concentration of sodium dodecyl sulphate. The mechanistic dissolution insights from the visualisation approach are evident. (c) 2012 Elsevier B.V. All rights reserved.