Estimation of Drug Particle Size in Intact Tablets by 2-Dimensional X-Ray Diffractometry

Seema Thakral, Naveen K. Thakral, Raj Suryanarayanan

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


The average grain size of a crystalline material can be determined from the γ-profile of Debye rings in 2-dimensional X-ray diffraction frames. Our objectives were to: (1) validate the method for organic powders and use it to determine the grain size in intact tablets, and (2) demonstrate the pharmaceutical application of this technique by determining the grain size of the active pharmaceutical ingredient in marketed formulations. Six sieve fractions of sucrose were prepared and the particle size distribution was confirmed by laser diffraction. Their average grain size was determined from the 2-dimensional X-ray diffraction frames by the γ-profile method. For particles <90 μm (based on sieving), the average particle size determined by the 3 methods were in good agreement. When these particles were compressed, there was no discernible change in the sucrose grain size in tablets. When the particles were >250 μm, compression resulted in a mixture of large grains and fine powder. The grain size of acetaminophen in 11 marketed tablet formulations was determined to be either ∼35 μm or ∼80 μm. This nondestructive technique can therefore be potentially useful to estimate the grain size of crystalline formulation components in intact tablets.

Original languageEnglish (US)
Pages (from-to)231-238
Number of pages8
JournalJournal of Pharmaceutical Sciences
Issue number1
StatePublished - Jan 2018

Bibliographical note

Funding Information:
The project was partially supported by the William and Mildred Peters endowment fund. The authors thank Bob He (Bruker) for the enlightening discussions. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Science, under contract No. DE-AC02-06CH11357. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. The authors dedicate this paper to Professor Samuel Yalkowsky. Though none of us formally trained with Professor Yalkowsky, we have learnt an immense amount from his published work.

Publisher Copyright:
© 2018 American Pharmacists Association®


  • X-ray diffraction
  • compression
  • dissolution
  • particle size
  • powders
  • tablets


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