Improving blend content uniformity via dry particle coating of micronized drug powders

Zhonghui Huang, Wannan Xiong, Kuriakose Kunnath, Sayani Bhaumik, Rajesh N. Davé

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Content uniformity of low dose blends with fine active pharmaceutical ingredients (API) is adversely impacted due to API agglomeration caused by high powder cohesion. Dry coating using high-intensity vibratory mixing is employed to reduce API cohesion and granular Bond number as well as agglomeration as predicted by contact models, hence improve blend content uniformity (CU). Micronized acetaminophen (mAPAP) (~ 10 μm), a model API, was dry coated with nano-silica R972P (20 nm), and mixed with Avicel 102. The amount of silica was varied from 0 to 2.74 wt%, corresponding to theoretical surface area coverage (SAC) from 0 to 100% respectively. Bulk density, unconfined yield strength, and dispersive surface energy results indicated dry coating with 0.27 to 1.0 wt% silica was adequate for API property enhancement; further corroborated by improved CU for 5 wt% API blends. Excellent CU was achieved for 3, 5 and 10 wt% API loaded blends, where 30 min of mixing was found to be acceptable for all three. The CU with dry coated mAPAP was significantly lower and within the acceptable range as compared to control blends without silica, as well as those with silica added during blending. Sieving of mAPAP illustrated the reduction in mAPAP agglomeration, necessary for improved CU after dry coating, corroborating model based predictions. Compared to theoretical predictions, actual CU was higher unless API agglomerate size distribution obtained via sieving was taken into account. Overall, cohesion reduction by dry coating is shown as a promising approach for improving content uniformity of cohesive API blends.

Original languageEnglish (US)
Pages (from-to)344-355
Number of pages12
JournalEuropean Journal of Pharmaceutical Sciences
StatePublished - Jun 15 2017

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Cohesive API powder
  • Content uniformity
  • Dry coating
  • Granular Bond number
  • Low dose blends


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