Powder segregation can cause severe issues in processes of pharmaceutical drugs for control of content uniformity if the powder is likely to be free or easy flowing. Assessing segregation intensity of formulated powders in a process is challenging at the formulation stage because of the limited availability of samples. An advanced segregation evaluation using small bench-scale testers can be useful for formulation decisions and suggestions of operation conditions in the process, which has not been practically investigated before. In this study, eight formulations (two co-processed excipients blended with one active pharmaceutical ingredient at different ratios) were used for the segregation study on two types of bench-scale testers (air-induced and surface rolling segregation tester), and a pilot simulation process rig as a comparative study. The results show that segregation measured on the bench-scale testers can give a good indication of the segregation intensity of a blend if the segregation intensity is not more than 20%. The comparison also shows that both the bench-scale testers have a good correlation to the process rig, respectively, which means either segregation tester can be used independently for the evaluation. A linear regression model was explored for prediction of segregation in the process.
Authors
Tong Deng, Lucas Massaro Sousa, Vivek Garg, Michael S A Bradley
- Bibliographic Reference
- Tong Deng, Lucas Massaro Sousa, Vivek Garg, Michael S A Bradley. Segregation of formulated powders in direct compression process and evaluations by small bench-scale testers. International Journal of Pharmaceutics, 2023, 647, pp.123544. ⟨10.1016/j.ijpharm.2023.123544⟩. ⟨hal-04289011⟩
- DOI
- https://doi.org/10.1016/j.ijpharm.2023.123544
- HAL Collection
- IFP Energies Nouvelles
- HAL Identifier
- 4289011
- Institution
- ['University of Greenwich', 'IFP Energies nouvelles']
- Published in
- France
Table of Contents
- Segregation of formulated powders in direct compression process and evaluations by small bench-scale testers 2
- 1 Introduction 2
- 2 Powder segregation in a direct compression process 2
- 2.1 Segregation mechanisms in the direct compression process 3
- 2.2 Influential factors on the powder segregation 3
- 2.3 Segregation indices used in this study 4
- 2.4 Segregation harshness factors 4
- 3 Materials and methods 5
- 3.1 Materials and formulations 5
- 3.2 Material characteristics 5
- 3.3 Experimental methods 6
- 3.3.1 Bench-scale segregation testers 6
- 3.3.2 Pilot simulation rig at the Wolfson Centre 7
- 3.3.3 Sample blending 8
- 3.3.4 Particle size analysis 8
- 3.3.5 Averaged and maximum SI 8
- 4 Results and discussion 9
- 4.1 Segregation tests on the bench-scale testers 9
- 4.2 Segregation tests on the pilot simulation rig 10
- 4.3 Influences of size span and angle of repose 10
- 4.4 Comparison between the bench-scale testers and the process rig 11
- 4.5 Linear regression model for segregation mechanisms 12
- 5 Conclusions 13
- CRediT authorship contribution statement 14
- Declaration of Competing Interest 14
- Data availability 14
- Acknowledgement 14
- References 14
