Tablet granulation process

Rudd, D. The use of acoustic monitoring for the control and scale-up of a tablet granulation process. J. Proc. Anal. Tech. 2004, 1 (2), 8-11. 

Berman J, Pierce P, Page PE (1994) Scrile-up of a spray dry tablet granulation process thermodynamic considerations. Drug Dev Ind Pharm 20(5) 731-755 Conference I, Harmonisation (1999) Specifications test procedures and a cceptance criteria for new drug substances and new drug products Q6A, (October)... 

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. 

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). 

M.D. Tousey, The Granulation Process 101 Basic Technologies for Tablet Making, available http //pharmtech. flndpharma.eom/pharmtech/data/articlestandard//pharmtech/432002/36208/article.pdf accessed 27 November 2009. 

Two additional experimental designs were carried out to optimize the formulation and granulation process (water addition time, granulating time, and addition of binder—dry versus in-solution— binder level, disintegrant level, and lubricant level). There was a trend toward improved compaction profiles and reduced friability with increased granulation time. It was also observed that the lubricant and disintegrant levels affected the friability of the tablets. The effect of the lubricant level on tablet friability is shown in Figure 20. The final formulation and process are summarized in Table 5. 

Granulation particle size distribution An extremely important parameter that can affect tablet compressibility, hardness, thickness, disintegration, dissolution, weight variation, and content uniformity. This parameter, which can be done by sieve analysis, should be monitored throughout the tablet validation process. 

This chapter focuses on the use of fluidized bed granulation process in the development and preparation of low-dose granule formulations for further conversion to immediate release tablets for personal administration. As a reference document, the chapter does not cover some very common subjects such as process safety, material characterization techniques and basic process and instrumentation technologies. Because the authors intention is to relate their experience in this specialized area, these areas are not discussed in any depth however their omission does not reduce their importance. 

In the case where stability issues prevent the pursuit of the preferred formulation, then it becomes more important to optimize the dry granulation process to achieve an improved uniformity of drug as a function of particle size. For these cases, it is important to consider the impact of the optimized granulation on tableting performance. Although it is important to consider the commercial manufacturing efficiency, the process challenges that impact quality are of primary importance. 

Fig. 7.9. Batch fluid bed spray granulator used to produce tablet granulations in the pharmaceutical industry. Air-flow necessary for fluidization is generated by a suction-fan (2) mounted in the top portion of the unit, directly driven by an electric motor. The air being used is heated to the desired temperature by an air heater (5). Prefilters remove all impurities at the air inlet (6). The material to be processed has been loaded into the material container (1). The container bottom consists of a perforated plate above which a fine mesh stainless steel retaining screen is fitted. Exhaust filters (7) mounted above the product container retain fines and dust. The granulating liquid (3) is sprayed as a fine mist through a mechanical or pneumatically actuated nozzle (4) onto the finely dispersed, fluidized material to form the desired agglomerates. (Courtesy Aeromatic AG.)...

Select and evaluate formulation process(es), such as tabletting, granulation, lyophilization, or microencapsulation. 

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