Effects of crystal habit on the sticking propensity of ibuprofenA case study

Here at Gamlen we are highlighting some of the fascinating and ground-breaking research that has been carried out by our customers in our Paper of the Month posts.

  • This study highlights the importance of Materials Science as a key aspect of Quality by Design (QbD).
  • The aim was to investigate the link between the particle habit, surface energy and punch sticking propensity of an API.
  • As the authors note, “One of the challenges often faced when trying to link these properties is punch sticking is not detected until full scale manufacture”. Gamlen data solves this problem allowing sticking propensity to be assessed before full scale manufacture.
  • Ibuprofen was recrystallised from four different solvents resulting in the four batches displaying diverse crystal habits but similar physio-chemical properties.
  • The four batches varied in terms of particle aspect ratio (width/length) with increasing solvent polarity resulting in increasing shape regularity
  • The sticking propensity of each batch was measured as detachment stress (the stress required to detach a tablet from the base of a die after compaction) using a Gamlen Powder Compaction Analyser.
  • It was found that sticking propensity increased with increasing particle aspect ratio.
  • A combination of experimental and computation surface energy techniques showed that that differences in crystal habit were linked to changes in specific surface energy with an increase in specific surface energy correlating to increased sticking propensity

Scanning electron micrographs of recrystallised ibuprofen showing changes in particle habit from; a) hexane b) toluene c) acetonitrile d) ethanol. All images captured using Å~100 magnification and scale bar is 100 μm.


The authors successfully linked the processing, structure, properties, and performance of Ibuprofen, demonstrating the central principle of Materials Science as described by the Materials Science tetrahedron. “The increase in the specific energy component is shown to correlate with the sticking propensity of ibuprofen. It is proposed that investigation of the chemical causality of sticking, for this API and others, using the techniques demonstrated in this paper will be of increasing importance.”

Note: In the paper the authors use a handheld device in combination with a Gamlen GTP-1 to measure detachment stress values. Our D-series instruments now feature an integrated detachment force measurement system, so these measurements are automatically taken immediately after compaction.