Scale-up of Fluid Bed Granulation Using a Scale-Independent Parameter and a Process Model.
fluid bed granulation
process model
scale-up
scaling parameter
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
05 May 2021
05 May 2021
Historique:
received:
06
10
2020
accepted:
06
04
2021
entrez:
6
5
2021
pubmed:
7
5
2021
medline:
25
5
2021
Statut:
epublish
Résumé
A practice-based approach for the scale-up of fluid bed granulation in the context of drug product development is presented and evaluated in this work in the context of clinical drug product manufacturing development. The approach is based on the use of a scale-independent parameter, the evaporation energy to drying capacity ratio (EE/DC), and a process model. The EE/DC ratio is used to quantify, in one scale-independent parameter, the combined effect of the most impacting process parameters and to identify the spray rates to be used at different scales to achieve similar granule moisture rate of change. The process model is used to de-risk scale-up, by allowing the consideration of equipment differences across scales and process dynamics, which are aspects not accounted for by the EE/DC ratio. This approach was tested by scaling up the fluid bed granulation process of two formulations, one placebo and one active, from laboratory to pilot scales. This work showed how it was possible to use a simple scale-up approach coupled with a process model to achieve right first-time scale-up of a fluid bed granulation process and show how a placebo formulation could be used instead of active material, first to define the process at laboratory scale and then to de-risk the scale-up, by identifying scale-dependent differences.
Identifiants
pubmed: 33954856
doi: 10.1208/s12249-021-02013-x
pii: 10.1208/s12249-021-02013-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
148Références
Bilgili E, Rosen LA, Ko JS, Chen A, Smith E, Fliszar K, et al. Experimental study of fluidized bed co-granulation of two active pharmaceutical ingredients: an industrial scale-up perspective. Part Sci Technol. 2011;29:285–309.
doi: 10.1080/02726351.2010.516803
Peng Y, Fan LT. Hydrodynamic characteristics of fluidization in liquid-solid tapered beds. Chem Eng Sci. 1996;52(14):2277–89.
doi: 10.1016/S0009-2509(97)00061-4
Hede PD, Bach P, Jensen AD. Validation of the flux number as scaling parameter for top-spray fluidised bed systems. Chem Eng Sci. 2008;63:815–28.
doi: 10.1016/j.ces.2007.10.017
Jones DM. Factors to consider in fluid-bed processing. Pharm Technol. 1985;9(4):50–62.
Horio M, Nonaka A, Sawa Y, Muchi I. A new similarity rule for fluidized bed scale up. AICHE J. 1986;32(9):1466–82.
doi: 10.1002/aic.690320908
Schæfer T, Wørts O. Control of fluidized bed granulation III: effect of inlet air temperature and liquid flow rate on granule size and size distribution. Control of moisture content of granules in the drying phase. Arch Pharm Chem Sci Ed. 1978;6:1–13.
Schaafsma SH, Vonk P, Segers P, Kossen NWF. Description of agglomerate growth. Powder Technol. 1998;97:183–90.
doi: 10.1016/S0032-5910(97)03399-8
Rajniak P, Multi-scale modeling of fluid bed granulation: recent development, CFD-DEM coupling and using gSolids environment. AIChE Annual Meeting. November 2014, Atlanta, GA, USA.
Levin M. Pharmaceutical process scale up. New York: Marcel Dekker Inc.; 2002.
Iveson SM, Litster JD, Hapgood K, Ennis BJ. Nucleation, growth and breakage phenomena in agitated wet granulation processes: a review. Powder Technol. 2001;117:3–39.
doi: 10.1016/S0032-5910(01)00313-8
Litster JD, Hapgood KP, Michaels JN, Sims A, Roberts M, Kameneni SK, et al. Liquid distribution in wet granulation: dimensionless spray flux. Powder Technol. 2001;114:32–9.
doi: 10.1016/S0032-5910(00)00259-X
Rambali B, Baert L, Massart DL. Scaling up of the fluidized bed granulation process. Int J Pharm. 2003;252:197–206.
doi: 10.1016/S0378-5173(02)00646-4
Burgschweiger J, Tsotsas E. Experimental investigation and modelling of continuous fluidized bed drying under steady-state and dynamic conditions. Chem Eng Sci. 2002;57:5021–38.
doi: 10.1016/S0009-2509(02)00424-4
Ierapetritou MG, Ramachandran R, editors. Process simulation and data modeling in solid oral drug development and manufacture. New York: Humana Press, Springer Science+Business Media LLC; 2016.
gPROMS FormulatedProducts Documentation, Release 1.6.1 - June 2020, Process Systems Enterprise Limited, London, United Kingdom.
Gavi E. Application of a mechanistic model of batch fluidized bed drying at laboratory and pilot scale. Dry Technol. 2020;38(8):1062–78.
doi: 10.1080/07373937.2019.1611594
Burgschweiger J, Groenewold H, Hirschmann C, Tsotsas E. From hygroscopic single particle to batch fluidized bed drying kinetics. Can J Chem Eng. 1999;77:333–41.
doi: 10.1002/cjce.5450770220