High-Shear Granulation Process

The composition of a powder mixture for granulation generally consists of an active pharmaceutical ingredient (API), a filler, a disintegrant (usually not included in controlled release tablets), and a binder. 

A high-shear wet-granulation process includes the following steps  

Loading all the ingredients into the mixing bowl, which can be accomplished by either of the following methods gravity feeding with manual or pneumatic valve, and vacuum feeding. 

Mixing of dry ingredients such as API, filler, and disintegrant, at high impeller and chopper speeds for a short period of time (2-5 min). Addition of a liquid binder (either binder solution or solvent) into the powder mixture, while both the impeller and the chopper are running at a low speed. 

Wet massing with both the impeller and the chopper running at a high speed. 

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M. Whitaker, G.R. Baker, J. Westrup, PA. Gonlding, D.R. Rndd, R.M. Belchamber and M.P Collins, Apphcation of aconstic emission to the monitoring and end point determination of a high shear granulation process, Int. J. Pharm., 205, 79-91 (2000). 

R Luukkonen, M. Fransson, I.N. Bjorn, J. Hautala, B. Lagerhohn and S. Folestad, Real-time assessment of granule and tablet properties using in-line data from a high-shear granulation process, J. Pharm. Sci., 97(2), 950-959 (2008). 

Sirois PJ, Craig GD. 2000. Scale-up of a high-shear granulation process using a normalized impeller work parameter. Pharm. Dev. Technol. 5(3) 365-374. 

Kiekens, F. Cordoba-Diaz, M. Remon, J.P. Influence of chopper and mixer speeds and microwave power level during the high-shear granulation process on the final granule characteristics. Drug Dev. Ind. Pharm. 1999, 25 (12), 1289-1293. 

Process Analytical Technology (PAT) has been shown to be able to monitor and control a high-shear granulation process and predict behavior upon scale-up. Through the exploitation of PAT, online control of the process may be achieved, which can mitigate... 

Rekhi, G.S. Caricofe, R.B. Parikh, D.M. Augsburger, L.L. A new approach to scale-up of a high-shear granulation process. Pharm. Tech. Suppl-TabGran. Yearbook 1996, 58-67. 

Rekhi G, Caricofe RB, Parikh DM, Augsburger LL. A New Approach to Scale-up of a High-Shear Granulation Process. Pharm Tech 1986 20(Suppl) 2-10. 

Horsthuis G, van Laarhoven JAH, van Rooji RBM, Vromans H. Studies on upscaling parameters of the Gral high shear granulation process. Int J Pharm 1993 92 143-50. 

High-shear granulation has been one of the most commonly used methods to produce granules since the early 1980s (4). Hence, this chapter discusses in detail, the equipment, process variables, formulation requirements, granulation end-point determination, and scale-up considerations of the high-shear granulation process. 

Horsthuis GJB, van Laarhoven JAH, van Rooij RCBM, Vromans H. Studies on upscaling parameters of the Oral high-shear granulation process. Int J Pharm 1993 92 143-150. Ameye D, Keleb E, Vervaet C, Remon Jean P, Adams E, Massart Desire L. Scaling-up of a lactose wet granulation process in Mi-Pro high shear mixers. Eur J Pharm Sci 2002 17 247-251. 

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