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 language | English |
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Pages (from-to) | 615-630 |
Number of pages | 16 |
Journal | International Journal of Pharmaceutics |
Volume | 566 |
Early online date | 31 May 2019 |
DOIs | |
Publication status | Published - 20 Jul 2019 |
Bibliographical note
Copyright © 2019 Elsevier B.V. All rights reserved.Funding
This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) ‘Modelling of Multi-Phase Transport Processes to Enable Automation in Manufacturing, (MOMEnTUM)’ and is co-funded under the European Regional Development Fund under Grant Number 14/SP/2750 , in partnership with Janssen Pharmaceuticals , Belgium. Appendix A
Keywords
- Compactibility
- Continuous direct compression
- Flow and compaction behaviour
- High dosage formulation
- Raw material characterization
- Systematic formulation development
ASJC Scopus subject areas
- Pharmaceutical Science