Tablet wet granulation

Although DC seems to be the method of choice for tableting, wet granulation is still widely used in various product manufacturing. Excipients such as MCC lose compressibility upon addition of water, a phenomenon called quasi-hornification (49). This property is improved, however, when it is coprocessed into SMCC. 

Kiortsis S. Kachrimanis K. Broussali T, Malamataris S. Drug relea.se from tableted wet granulations comprising cellulosic (HPMC or HPC) and hydrophobic component. Eur j Pharm Biofrfuum 2005 59( I ) 73-83. 

The adhesive and binding power is particularly important in tabletting (wet granulation, dry granulation, direct compression). This property is also useful in film coatings and adhesive gels. 

Fig. 37. Influence of compression force on the hardness of calcium hydrogen phosphate tablets (wet granulation)...

Uses Binder for pharmaceutical tablet wet granulation thickener, stabilizer, binder, emulsifier in foods... 

For successful tableting, a material must have suitable flow properties to allow it to be fed to the tableting machine. Wet or dry granulation is used to improve the flow properties of materials. In the case of wet granulation, agitative granulation techniques such as fluidized beds or mixer granulators as discussed above are often employed. 

Enzymes. Where tablets are not naturally very cohesive and have thus been manufactured by a wet granulation process involving one of the binders listed in Table 8, addition of small quantities of appropriate enzyme may be sufficient to produce rapid disintegration. It has also been proposed that disintegration action might result from expansion of the entrapped air due to generation of heat of wetting when the tablet is placed in a fluid. This concept has received little attention. 

Khattab, L, Menon, A., and Sakr, A., Effect of mode of incorporation of disintegrants on the characteristics of fluid-bed wet-granulated tablets, J. Pharm. Pharmacol., 45 687-691 (1993). 

Becker, D., Rigassi, T., and Bauer-Brandl, A., Effectiveness of binders in wet granulation A comparison using model formulations of different tabletability, Drug Dev. Ind. Pharm., 23 791-808 (1997). 

Desai et al. [86] reported on the photolytic degradation of the anti-viral, sorivudine, which formed the inactive Z-isomer. On the basis of extensive dmg-excipient compatibility studies it was found that the incorporation of iron oxide pigments into the blends (direct compression or wet granulated) stabilised the dmg to photodegradation indeed, so much so that the tablet was found not to require a film coat. The data are summarised in Table 2.6. 

In pharmaceutical applications, sorbitol is used as a tablet diluent in wet granulation or dry compression formulations. It is commonly used in chewable tablets because of its sweet taste, and it is also used as a plasticizer for gelatin in capsule formulations. Sorbitol is utilized in sugar-free liquid preparations and as a stabilizer for drug, vitamin, and antacid suspensions. When it is used in syrups, crystallization around bottle caps is prevented. 

Figure 3 displays the results for a wet granulated product run at three speeds and three forces in production. The same speeds and similar forces were used on the Presster. Thirty tablets were produced at each speed. It can be seen that although the absolute hardness values differ by 1-2 kP in some cases (most likely due to differences in the two hardness testers used), the range of the window for the hardness values is comparable between the two machines. 

Figure 3 Ovaloid tablets ( 17mm length), wet granulation hardness (kP) profile.

In Figure 4, data from a low dose wet granulation formulation produced in production on a Courtoy R100/36 is compared to the Presster tablet hardness data. The force-hardness data from the two machines was comparable. 

After scale-up into production, it was determined that an increase in moisture content would improve the formulation stability for a high dose wet granulated product. It was decided to use the Presster to predict the results that would be obtained in production when the moisture content of the final blend was increased. Blends with three moisture levels were compressed at two forces. As shown in Figure 5, as moisture content increases, tablet hardness increased. The dissolution profiles for the tablets with different moisture levels were compared and found to be within specification, indicating that raising the moisture content in the final blend should result in acceptable tablets in production. 

Figure 11 Factors affecting flow of a tableting mixture prepared by wet granulation.

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