Direct Compression Tablet Containing 99% Active Ingredient—A Tale of Spherical Crystallization

Hongbo Chen, Aktham Aburub, Changquan Calvin Sun

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13 Scopus citations


Direct compression (DC) is the easiest and most cost-effective process for tablet manufacturing, because it only involves blending and compression. However, active pharmaceutical ingredients generally exhibit poor mechanical and micromeritic properties, which necessitate dilution and the use of high percentage of excipients to enable a robust DC manufacturing process. Consequently, drug loading in DC tablets is usually low (typically <30%, w/w). In this study, spherical crystallization by the quasi-emulsion solvent diffusion method was used to engineer a poorly flowing model compound, ferulic acid (FA), to attain superior mechanical properties, particle size distribution, and morphology. The engineered FA particles enabled the successful development of DC tablets containing 99% FA, which is in sharp contrast to the maximum 10% FA loading using as-received FA. The record high active pharmaceutical ingredient loading in this work illustrates the potential for spherical crystallization to enable high drug loading when developing a tablet product using the DC manufacturing process.

Original languageEnglish (US)
Pages (from-to)1396-1400
Number of pages5
JournalJournal of Pharmaceutical Sciences
Issue number4
StatePublished - Apr 2019

Bibliographical note

Funding Information:
This work was supported by a grant from Eli Lilly and Company through the Lilly Research Award Program. Part of this work was carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. We also thank the Chinese Scholarship Council for partial financial support to H.C.

Publisher Copyright:
© 2019 American Pharmacists Association®


  • API loading
  • direct compression
  • flowability
  • quasi-emulsion solvent diffusion
  • tabletability


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