Impact of Silica Dry Coprocessing with API and Blend Mixing Time on Blend Flowability and Drug Content Uniformity

Sangah S. Kim, Ameera Seetahal, Nicholas Amores, Christopher Kossor, Rajesh N. Davé

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


This paper considers two fine-sized (d50 ∼10 µm) model drugs, acetaminophen (mAPAP) and ibuprofen (Ibu), to examine the effect of API dry coprocessing on their multi-component medium DL (30 wt%) blends with fine excipients. The impact of blend mixing time on the bulk properties such as flowability, bulk density, and agglomeration was studied. The hypothesis tested is that blends with fine APIs at medium DL require good blend flowability to have good blend uniformity (BU). Moreover, the good flowability could be achieved through dry coating with hydrophobic (R972P) silica, which reduces agglomeration of not only fine API, but also of its blends while using fine excipients. For uncoated APIs, the blend flowability was poor, i.e. cohesive regime at all mixing times, and the blends failed to achieve acceptable BU. In contrast, for dry coated APIs, their blend flowability improved to easy-flow regime or better, improving with mixing time, and as hypothesized, all blends consequently achieved desired BU. All dry coated API blends exhibited improved bulk density and reduced agglomeration, attributed to mixing induced synergistic property enhancements, likely due to silica transfer. Despite coating with hydrophobic silica, tablet dissolution was improved, attributed to the reduced agglomeration of fine API.

Original languageEnglish (US)
Pages (from-to)2124-2136
Number of pages13
JournalJournal of Pharmaceutical Sciences
Issue number8
StatePublished - Aug 2023

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Blend processability
  • Cohesive powder blends
  • Dry coating
  • Mixing effect
  • Particle morphology impact


Dive into the research topics of 'Impact of Silica Dry Coprocessing with API and Blend Mixing Time on Blend Flowability and Drug Content Uniformity'. Together they form a unique fingerprint.

Cite this