Systematic development of a high dosage formulation to enable direct compression of a poorly flowing API

A case study

Barbara E. Schaller, Kevin M. Moroney, Bernardo Castro-Dominguez, Patrick Cronin, Jorge Belen-Girona, Patrick Ruane, Denise M. Croker, Gavin M. Walker

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

In this work, the transfer of oral solid dosage forms, currently manufactured via wet granulation, to a continuous direct compression process was considered. Two main challenges were addressed: (1) a poorly flowing API (Canagliflozin) and (2) high drug loading (51 wt%). A scientific approach was utilised for formulation development, targeting flow and compaction behaviour suitable for manufacturing scale. This was achieved through systematic screening of excipients to identify feasible formulations. Targeted design of experiments based on factors such as formulation mixture and processing parameters were utilised to investigate key responses for tablet properties, flow and compaction behaviour. Flow behaviour was primarily evaluated from percentage compressibility and shear cell testing on a powder flow rheometer (FT4). The compaction behaviour was studied using a compaction simulator (Gamlen). The relationships between tablet porosity, tensile strength and compaction pressure were used to evaluate tabletability, compactibility and compressibility to assess scale-up. The success of this design procedure is illustrated by scaling up from the compaction simulator to a Riva Piccola rotary tablet press, while maintaining critical quality attributes (CQAs). Compactibility was identified as a suitable scale-up relationship. The developed procedure should allow accelerated development of formulations for continuous direct compression.

Original languageEnglish
Pages (from-to)615-630
Number of pages16
JournalInternational Journal of Pharmaceutics
Volume566
Early online date31 May 2019
DOIs
Publication statusPublished - 20 Jul 2019

Keywords

  • Compactibility
  • Continuous direct compression
  • Flow and compaction behaviour
  • High dosage formulation
  • Raw material characterization
  • Systematic formulation development

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Systematic development of a high dosage formulation to enable direct compression of a poorly flowing API : A case study. / Schaller, Barbara E.; Moroney, Kevin M.; Castro-Dominguez, Bernardo; Cronin, Patrick; Belen-Girona, Jorge; Ruane, Patrick; Croker, Denise M.; Walker, Gavin M.

In: International Journal of Pharmaceutics, Vol. 566, 20.07.2019, p. 615-630.

Research output: Contribution to journalArticle

Schaller, Barbara E. ; Moroney, Kevin M. ; Castro-Dominguez, Bernardo ; Cronin, Patrick ; Belen-Girona, Jorge ; Ruane, Patrick ; Croker, Denise M. ; Walker, Gavin M. / Systematic development of a high dosage formulation to enable direct compression of a poorly flowing API : A case study. In: International Journal of Pharmaceutics. 2019 ; Vol. 566. pp. 615-630.
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