Surface engineered excipients: III. Facilitating direct compaction tableting of binary blends containing fine cohesive poorly-compactable APIs

Liang Chen, Zizhou He, Kuriakose T. Kunnath, Siqi Fan, Yuhan Wei, Xiaoyi Ding, Kai Zheng, Rajesh N. Davé

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Direct compaction tableting, a desired manufacturing option, is infeasible for blends containing fine cohesive poorly-compactable APIs at higher drug loadings. In this study, the feasibility of using fine, dry coated excipients is investigated instead of dry coating of the APIs, as was done previously. Avicel PH-105 (20.1 µm) dry coated with 1 wt% hydrophilic silica A200 as an engineered excipient was blended with fine (11.3 µm) or semi-fine (30.2 µm) Acetaminophen, or Ibuprofen 50 (55.4 µm) in binary blends at low, medium and high drug loadings (10%, 30%, 60%). The blend uniformity, bulk density, flowability, as well as tablet properties such as friability, weight variation and strength demonstrate overall better performance compared to blends with Avicel PH-105, Prosolv 50 or Prosolv 90 as the excipient. These results along with processability maps of bulk density vs. FFC and tablet tensile strength vs. FFC indicate dry coated Avicel PH-105 could enable direct compaction for IBU50 and cAPAP at all drug loadings, and up to 30% drug loading for mAPAP. In contrast, Prosolv 90 failed for IBU50 at 60% drug loading, and for mAPAP at all drug loadings. Prosolv 50 could only enable direct compaction for IBU50 at all drug loadings. These unexpected outcomes suggest that for direct compaction of very fine, cohesive APIs at higher drug loadings, surface modified fine excipients perform better. A surprising outcome is the improvement in tablet strength for blends with dry coated Avicel PH-105 compared to uncoated Avicel PH-105 at higher drug loading, especially considering parts I and II showed that silica dry coating decreases the placebo tablet tensile strength.

Original languageEnglish (US)
Pages (from-to)354-365
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume557
DOIs
StatePublished - Feb 25 2019

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Blends
  • Cohesive APIs
  • Direct compaction
  • Excipients
  • Particle engineering
  • Processability
  • Tablet

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