Wet Granulation Systems

The variety of mechanical granulation systems is very highly justified with the manifold requirements of the formulations on the market. The various system available on the 

Product holding time or dwell time and energy input cannot be seen as separated from each other. Only the combination of both enables a predietion of the granulation characteristics of the machine. Especially in the case of hardly soluble substances or raw materials with a need for intensive blending either a high holding 

Product holdup (product staying inside the machine after granulation) is of importance during the drug development phase as it limits the minimum batch size possible. The larger the batch size the less important is the product holdup of the machine as it is a constant value independent of the total batch size. Nevertheless, a low product holdup helps in reducing waste and thus helps in cleaning. 

A lot of mechanical continuous granulation equipment can be seen as derived from single-or twin-screw extrusion systems, mostly improved with special fixtures inside like choppers or baffles to fulfill the needs of pharmaceutical wet granulation processes. Screw extrusion systems are treated elsewhere in this book and will not be discussed at this point. 

Other machines like the Schugi mixer-agglomerator (Hosokawa Schugi B.V., Lelystadt, The Netherlands) or the Nica M6 turbine mixer and granulator (Aero-matic-Fielder Ltd., Eastleigh, U.K.) were already mentioned and discussed in the last edition of this book. 

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Rudnic, E.M., Kanig, J., and Rhodes, C.T., The effect of molecular structure on the function of sodium starch glycolate in wet granulated systems. Drug Dev. Ind Pharm., 9 303-320 (1983). 

This sort of system can prepare a batch of granules in 60-90 minutes. However, whereas fluidised bed granulation is rapid and flexible it is not without its problems. The presence of finely divided powders means that the apparatus itself is a potential explosion hazard, although, obviously, these systems are constructed and used in such a way as to be safe. One possibility is to use nitrogen instead of air thus providing an inert atmosphere. A further problem is that a fluidised bed granulator is not the easiest piece of equipment to set up, particularly compared with a wet granulation system. 

Buckton G, Adeniyi AA, Saunders M. Ambarkhanc A, HyperDSC studies of amorphous polyvinylpyrrolidone in a model wet granulation system. Int J Pharm 2006 312(1-2) 61-5. 

The classic wet granulation system with spheronizing is shown in Figure 398. It consists of equipment for mixing and wetting the powder components, kneading the wet formulation, extruding damp cylindrical pellets,... 

Figure 398. Flow diagram of a continuous wet granulation system with spheronizing. (Courtesy of Russel Finex, London, England)...

Figure 411. General flow sheet of conventional wet granulation systems for fertilizers. Granulators (a) drum and ammoniator , (b) pan, (c) spray dryer and prilling tower, (d) fluidized bed, (e) mixer.

Bucarban tablets were selected as a model for wet granulation systems Originally both intra- and extragrginular disintegrant is corn starch in this formulation. In our experiment CDP was replaced instead of corn starch in 3 different ways /Table II/ The characteristics of tablets are given in Table V and the dissolution curves are presented on Fig 5 ... 

S. Watano, Direct control of wet granulation processes by image processing system, Powder TechnoL, 117(1-2), 163-172 (2001). 

Two polymers were incorporated in the inert matrix system ethylcellulose and polyvinyl chloride. The processes used to prepare tablets containing such polymers often include direct compression [4-6], wet granulation [7,8], coating [9-11] and, rarely, dry granulation [12]. 

One of the major flaws in dry granulation for low-dose products is the granulation efficiency is lower than wet granulation. The material that bypasses the rolls, referred to as bypass, is the source of the incomplete granulation by roller compaction. Equipment factors that affect bypass in the feed system, roller compaction system and mill system are the focus of the discussion below. 

Ancillary Equipment Most instruments are based on the analysis of circulating wet suspensions. This set-up is unsuitable for brittle material and many manufacturers provide agitator cells to reduce breakage. Waste disposal is a major problem with some materials and this is reduced by the use of small volume cells (< 125 ml). Cells are also provided for corrosive liquid systems. Instruments can be set up to analyze falling streams of dry powders this is particularly suitable for brittle or soft (wet granules) materials. Deagglomerators are often provided for sticky dry powders. 

There are other ideas floating around, for example, use of neural network to describe and predict the behavior of the wet granulation or control the end-point by rapid image processing system. 

Two geometrically similar systems are called kinematically similar if they have the same ratio of velocities between the corresponding system points. Two kinematically similar systems are dynamically similar when they have the same ratio of forces between the corresponding points. Dynamic similitude for wet granulation would imply that the wet mass flow patterns in the bowl are similar. 

Kay, D. Record, P.C. Automatic wet granulation endpoint control system. Manuf. Chem. Aerosol News 1978, 9, 45 6. 

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