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Understanding Dynamics of Polymorphic Conversion during the Tableting Process Using In Situ Mechanical Raman Spectroscopy.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-07-07 , DOI: 10.1021/acs.molpharmaceut.0c00460
Heejun Park 1 , Haichen Nie 2 , Abhijeet Dhiman 3 , Vikas Tomar 3 , Qi Tony Zhou 1
Affiliation  

The objective of this study is to achieve a fundamental understanding of polymorphic interconversion during the tableting process, including during compaction, dwell, decompression/unloading, and ejection using an in situ mechanical Raman spectroscopy. The fit-for-purpose in situ mechanical Raman spectroscopy developed herein can provide simultaneous measurement of Raman spectra and densification for the powder compacts. Chlorpropamide (CPA), an antidiabetic drug, was selected as a model pharmaceutical compound because of its mechanical shear-induced polymorphic conversions. The results confirm that CPA polymorph A (CPA-A) was transformed to CPA polymorph C (CPA-C) under different compaction stresses. We also observed that the converted polymorph CPA-C could be reverted to the CPA-A due to the elastic recovery of powder compacts as detected during dwelling and unloading. This study is the first depiction of the dynamics of CPA polymorphic interconversion during compression, dwell, unloading, and ejection. Mechanistically, this study illustrates a correlation between the change in the powder compact’s relative density and polymorphic interconversion of the drug substance in different solid-state forms. The present research suggests that the process-induced polymorph conversion is a complicated dynamic process, which could be affected by the compaction pressure, the elasticity/plasticity of the material, the level of elastic recovery, and the dissipation of residual stress. In summary, this study demonstrates that the in situ mechanical Raman spectroscopy approach enables the simultaneous detection of mechanical and chemical information of the powder compact throughout the tableting process.

中文翻译:

使用原位机械拉曼光谱了解压片过程中多态转化的动力学。

这项研究的目的是在压片过程中,包括在压实,保压,减压/卸载和使用原位机械拉曼光谱法进行射出过程中,实现对多态互变的基本了解。适合现场使用本文开发的机械拉曼光谱可以同时测量粉末压坯的拉曼光谱和致密化。由于其机械剪切诱导的多晶型转化,选择一种抗糖尿病药物氯丙酰胺(CPA)作为模型药物。结果证实,在不同的压实应力下,CPA多晶型物A(CPA-A)转变为CPA多晶型物C(CPA-C)。我们还观察到,由于在居住和卸载过程中检测到粉末压块的弹性恢复,转化后的多晶型物CPA-C可以还原为CPA-A。这项研究是对压缩,驻留,卸载和弹出过程中CPA多态互变动力学的首次描述。机械上,这项研究说明了粉末压块相对密度的变化与药物以不同固态形式的多晶型相互转化之间的相关性。目前的研究表明,过程诱导的多晶型物转化是一个复杂的动力学过程,它可能受到压实压力,材料的弹性/塑性,弹性回复水平和残余应力消散的影响。总而言之,这项研究表明 以及消除残余应力。总而言之,这项研究表明 以及消除残余应力。总而言之,这项研究表明原位机械拉曼光谱方法可在制片过程中同时检测粉状压块的机械和化学信息。
更新日期:2020-08-03
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