Polymorph stabilization in processed acetaminophen powders

Anna Łuczak, Laila J. Jallo, Rajesh N. Dave, Zafar Iqbal

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


A novel approach has been developed to stabilize the metastable form II of acetaminophen (APAP) prepared from the melt of micronized and nano-silica coated APAP I. It is suggested that stabilization of form II APAP occurs by pinning via van der Waals-type interactions on low energy defects created by micronization and impinging particles during dry coating in form I APAP, heating to the melt phase, and cooling. The defects are likely to persist into the near-molten isotropic phase due to a permanent memory effect similar to that previously observed in silica-liquid crystal composites and re-crystallize together with form II APAP. Raman spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and conventional as well as intrinsic dissolution have been used to characterize the stabilized APAP II obtained. Raman measurements up to 18. months and PXRD data for micronized form II APAP show no indication of APAP I formation. Aged samples of dry-coated APAP II however display Raman features indicative of APAP I within 5. months. PXRD and SEM techniques also detected small fractions of APAP I in dry-coated APAP II. Both micronized APAP II and dry-coated APAP II give rise to a time-dependent background scattering superimposed on the Raman spectra which increases in integrated intensity with time, saturates at 180 and 90. days, respectively, and then decreases in intensity with further aging. The time-dependent scattering background occurs in the stabilized form II APAP samples only after cooling from the melt and is more intense in micronized APAP II compared to dry-coated APAP II. It is assigned to disorder associated with slowly diffusing defects created by micronization and dry coating with impinging nano-silica particles in form I APAP. Intrinsic dissolution profiles for the stabilized APAP II samples showed measureable increases, particularly for micronized APAP II.

Original languageEnglish (US)
Pages (from-to)52-62
Number of pages11
JournalPowder Technology
StatePublished - Feb 2013

All Science Journal Classification (ASJC) codes

  • General Chemical Engineering


  • Dissolution
  • Dry coating
  • Polymorphs
  • Raman spectroscopy
  • Stabilization


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