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Understanding Dynamics of Polymorphic Conversion during the Tableting Process Using In Situ Mechanical Raman
Heejun Park1, Haichen Nie2, Abhijeet Dhiman3
1Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.
Molecular Pharmaceutics
|July 8, 2020
Summary
This study reveals how pharmaceutical powders change solid-state forms during tableting. Using in situ mechanical Raman spectroscopy, we observed polymorphic interconversion in chlorpropamide (CPA) under compaction stress and elastic recovery.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Chemical Engineering
Background:
- Polymorphic interconversion is critical in pharmaceutical manufacturing.
- Understanding solid-state transformations during tableting is essential for drug product quality.
- Chlorpropamide (CPA) is known to undergo mechanical shear-induced polymorphic conversions.
Purpose of the Study:
- To fundamentally understand polymorphic interconversion during the tableting process.
- To develop and utilize in situ mechanical Raman spectroscopy for simultaneous measurement of Raman spectra and densification.
- To investigate the dynamics of polymorphic interconversion in chlorpropamide (CPA) during compaction, dwell, decompression, and ejection.
Main Methods:
- Development of a fit-for-purpose in situ mechanical Raman spectroscopy technique.
- Simultaneous measurement of Raman spectra and powder compact densification.
- Utilizing chlorpropamide (CPA) as a model pharmaceutical compound with known polymorphic conversions.
Main Results:
- Confirmed transformation of CPA polymorph A (CPA-A) to CPA polymorph C (CPA-C) under compaction stress.
- Observed reversion of CPA-C to CPA-A during dwelling and unloading due to elastic recovery.
- Demonstrated a correlation between powder compact relative density changes and polymorphic interconversion.
Conclusions:
- Process-induced polymorph conversion is a dynamic process influenced by compaction pressure, material properties, elastic recovery, and stress dissipation.
- In situ mechanical Raman spectroscopy enables simultaneous detection of mechanical and chemical information during tableting.
- The study provides the first dynamic depiction of CPA polymorphic interconversion throughout the tableting cycle.
Keywords:
chlorpropamidedeformationin situ mechanical Raman spectroscopypolymorphic interconversiontabletingMore Related Videos
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