Topologically directed confocal Raman imaging (TD-CRI): Advanced Raman imaging towards compositional and micromeritic profiling of a commercial tablet components

Prakash Muthudoss, Satheesh Kumar, Eddy Yii Chung Ann, Kwok Jia Young, Rayce Lim Rui Chi, Ravikiran Allada, Balaji Jayagopal, Anil Dubala, Irfan B. Babla, Samir Das, Sandeep Mhetre, Isha Saraf, Amrit Paudel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Particle size distribution (PSD), spatial location and particle cluster size of ingredients, polymorphism, compositional distribution of a pharmaceutical product are few of the most important attributes in establishing the drug release-controlling microstructural and solid state properties that would be used to (re)design or reproduce similar products. There are numerous solid-state techniques available for PSD analysis. Laser diffraction (LD) is mostly used to study PSD of raw materials. However, a constraint of LD is the interference between the active pharmaceutical ingredients (API) and excipients, where it is very challenging to measure API size in a tablet. X-ray powder diffraction (XRPD) is widely employed in establishing the polymorphism of API and excipients. This research examined a commercial osmotic tablet in terms of extracting solid state properties of API and functional excipient by Raman Imaging. Establishing repeatability, reproducibility, and sample representativeness when the samples are non-uniform and inhomogeneous necessitates multiple measurements. In such scenarios, when employing imaging-based techniques, it can be time-consuming and tedious. Advanced statistical methodologies are used to overcome these disadvantages and expedite the characterization process. Overall, this study demonstrates that Raman imaging can be employed as a non-invasive and effective offline method for assessing the solid-state characteristics of API and functional excipients in complex dosage forms like osmotic tablets.

Original languageEnglish
Article number114581
JournalJournal of Pharmaceutical and Biomedical Analysis
Publication statusPublished - 20 Feb 2022


  • Bootstrapping
  • Cluster size distribution
  • Compositional distribution
  • Control chart
  • Non-parametric statistical tests
  • Osmotic drug delivery systems
  • Particle size distribution
  • Polymorphism
  • Raman imaging
  • Solid-state properties
  • Spatial location

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry


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