Solid-state property modification and dissolution rate enhancement of tolfenamic acid by supercritical antisolvent process

Hung Hsin Chen, Chie Shaan Su, Jun Jen Liu, Ming Thau Sheu

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


In this study, the supercritical antisolvent (SAS) process is applied to crystallization of an active pharmaceutical ingredient, tolfenamic acid, using carbon dioxide as the antisolvent. Six operating parameters in the SAS process including solvent system, operating temperature, operating pressure, solution concentration, solution flow rate and nozzle diameter are studied. The effects of operating parameters on solid-state properties of the processed tolfenamic acid including crystal habit, mean particle size and polymorphic form are compared and discussed. The crystal habit of original tolfenamic acid crystals is irregular shape with Form I polymorph. The mean particle size of original powders is about 30 μm. After recrystallization using SAS process, two polymorphic forms of tolfenamic acid with different crystal habits and mean particle sizes are obtained. Form I tolfenamic acid shows a needle-like crystal habit with mean particle size of about 20 μm; while Form II tolfenamic acid shows a rod-like crystal habit with mean particle size of around 10 μm. In addition, the dissolution profiles of original and recrystallized tolfenamic acids are also studied and compared. Experimental results show that the recrystallized Form II tolfenamic acid crystals has an enhanced dissolution rate compared with the original sample, demonstrating that the SAS technology is an efficient process for controlling and modifying the solid-state properties of tolfenamic acid and also produces microparticles with enhanced dissolution behavior.

Original languageEnglish
Pages (from-to)17-23
Number of pages7
JournalJournal of Supercritical Fluids
Publication statusPublished - 2015


  • Carbon dioxide
  • Recrystallization
  • Supercritical antisolvent
  • Tolfenamic acid

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Chemical Engineering(all)
  • Condensed Matter Physics


Dive into the research topics of 'Solid-state property modification and dissolution rate enhancement of tolfenamic acid by supercritical antisolvent process'. Together they form a unique fingerprint.

Cite this