Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2007 September; 8(3): E118–E125.
Published online 2007 August 10. doi:  10.1208/pt0803066
PMCID: PMC2750563

An energy-based population-balance approach to model granule growth and breakage in high-shear wet granulation processes


A mathematical model of high shear wet granulation is proposed, where granule breakage, and not growth, is the dominant process. The energy required for granule breakage is assumed to be provided by the impact of granules between themselves and the granulator parts, and the extent of granule breakage determined by the balance between the impactenergy and the work of adhesion between the agglomerating particles. A specific volume of dry powder per unit crack surface area was allowed to reattach to the surface of broken granules to account for granule growth. To verify proposed model conditions, lactose monohydrate was granulated with a relatively low amount (6%) of the binder phase, polyvinyl-pyrrolidone and water, and was added to the powder before granulation.

The trend in granule size distribution during the experiment closely follwed the predicted model with an initial increase in the weight fraction of the larger granules. This increase was possibly due to extensive breakage of weaker granules and less extensive breakage, as if by attrition, of stronger granules, accompanied by the attachment of dry powder to the cracked surfaces. Eventually, larger granules experience increased impact energy and break. When excess binder is added and, higher volumes of powder reattach to the crack surface, more large granules form leading to granule overgrowth. This model highlights the importance of the probability of impact per unit time interval (ie, the rate of impact), the strength of the granules and the volume of powder that could attach to the cracked surface in high shear granulation processes where significant granule breakage is encountered.

Keywords: High shear granulation, population blance, model, granule breakage

Full Text

The Full Text of this article is available as a PDF (387K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. 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. [Cross Ref]
2. Wehrlé P, Nobelis Ph, Cuiné A, Stamm A. Scaling-up of wet granulation: a statistical methodology. Drug Dev Ind Pharm. 1993;19:1983–1997. doi: 10.3109/03639049309069336. [Cross Ref]
3. Sirois PJ, Craig GD. Scaleup of a high-shear granulation process using a normalized impeller work parameter. Pharm Dev Tech. 2000;5:365–374. doi: 10.1081/PDT-100100552. [PubMed] [Cross Ref]
4. Litster JD. Scaleup of wet granulation processes: science not art. Powder Technol. 2003;130:35–40. doi: 10.1016/S0032-5910(02)00222-X. [Cross Ref]
5. Litster JD, Hapgood KP, Michaels JN, Sims A, Roberts M, Kameneni SK. Scale-up of mixer granulators for effective liquid distribution. Powder Technol. 2002;124:272–280. doi: 10.1016/S0032-5910(02)00023-2. [Cross Ref]
6. Leuenberger H. Scale-up of granulation processes with reference to process monitoring. Acta Pharm Technol. 1983;29:274–280.
7. Ameye D, Keleb E, Vervaet C, Remon JP, Adams E, Massart DL. Scaling-up of a lactose wet granulation process in Mi-Pro high shear mixers. Eur J Pharm Sci. 2002;17:247–251. doi: 10.1016/S0928-0987(02)00218-X. [PubMed] [Cross Ref]
8. Talu I, Tardos GI, Khan MI. Computer simulation of wet granulation. Powder Technol. 2000;110:59–75. doi: 10.1016/S0032-5910(99)00268-5. [Cross Ref]
9. Faure A, York P, Rowe RC. Process control and scale-up of pharmaceutical wet granulation processes: a review. Eur J Pharm Biopharm. 2001;52:269–277. doi: 10.1016/S0939-6411(01)00184-9. [PubMed] [Cross Ref]
10. Wauters PAL, Scarlett B, Liu LX, Litster JD, Meesters GMH. A population balance model for high shear granulation. Chem Eng Commun. 2003;190:1309–1334. doi: 10.1080/00986440302147. [Cross Ref]
11. Verkoeijen D, Pouw GA, Meesters GMH, Scarlett B. Population balances for particulate processes: a volume approach. Chem Eng Sci. 2002;57:2287–2303. doi: 10.1016/S0009-2509(02)00118-5. [Cross Ref]
12. Ramkrishna D, Mahoney AW. Population balance modeling: promise for the future. Chem Eng Sci. 2002;57:595–606. doi: 10.1016/S0009-2509(01)00386-4. [Cross Ref]
13. McCoy BJ. A population balance framework for nucleation, growth, and aggregation. Chem Eng Sci. 2002;57:2279–2285. doi: 10.1016/S0009-2509(02)00117-3. [Cross Ref]
14. Hounslow MJ, Ryall RL, Marshall VR. A discretized population balance for nucleation, growth, and aggregation. AIChE J. 1988;34:1821–1832. doi: 10.1002/aic.690341108. [Cross Ref]
15. Liu LX, Litster JD. Population balance modeling of granulation with a physically based coalescence kernel. Chem Eng Sci. 2002;57:2183–2191. doi: 10.1016/S0009-2509(02)00110-0. [Cross Ref]
16. Maurstad O. Population Balance Modeling of Agglomeration in Granulation Processes [PhD Thesis] Trondheim, Norway: Norges teknisk-naturvitenskapelige universitet (Norwegian University of Science and Technology), Institutt for termisk energi og vannkraft (Department of Thermal Energy and Hydropower); 2002.
17. Immanuel CD, Doyle FJ. Computationally efficient solution of population balance models incorporating nucleation, growth and coagulation: application to emulsion polymerization. Chem Eng Sci. 2003;58:3681–3698. doi: 10.1016/S0009-2509(03)00216-1. [Cross Ref]
18. Litster J, Ennis B, editors. The Science and Engineering of Granulation Processes. Boston, MA: Kluwer Academic Publishers; 2004.
19. Bond FC. Some recent advances in grinding theory and practice. Brit Chem Eng. 1963;8:631–643.
20. Bela B. Principles of Comminution. Budapest, Hungary: Akadeìmiai Kiadoì; 1964.
21. Plank R, Diehl B, Grinstead H, Zega J. Quantifying liquid coverage and powder flux in high-shear granulators. Powder Technol. 2003;134:223–234. doi: 10.1016/S0032-5910(03)00171-2. [Cross Ref]
22. Litster JD, Hapgood KP, Michaels JN, et al. Liquid distribution in wet granulation: dimensionless spray flux. Powder Technol. 2001;114:32–39. doi: 10.1016/S0032-5910(00)00259-X. [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists