Tableting process compaction

Successful scale-up of the tableting process also requires control of the raw materials used in compaction. Typically, pharmaceutical excipients vary in their physicochemical properties, which result in batch-to-batch variations. The tableting process, especially direct compression processes where there is limited raw material alteration before compaction, is susceptible to raw material variation, which may be magnified upon scale-up. Compaction science affords the ability to fingerprint raw materials, including the drug substance, to determine if the same compaction properties will be observed from batch to batch. This also allows for a rational approach for determining alternate vendor sources of the same materials. 

To consider the subject of scale-up of the compaction and tableting process, one must consider the production of one tablet in 30 minutes, if one were a new graduate student using the Carver Hydraulic Laboratory Press for the first time, to a single-stroke Model E or Model F press at 60 tablets per minute, to a full-scale rotary tablet press at more than 2000 tablets per minute. 

It was demonstrated that dimensional analysis of the tableting process can produce a scientifically reliable way of predicting tablet properties across the range of materials and with diverse compaction mechanisms. A theoretically sound scale-up method is thus readily available for tableting equipment of different capacity. The method can be readily expanded to include other materials and tablet presses and other target quantities, such as tablet stability (disintegration) and bioavailability (dissolution). 

Using mechanical compaction simulators allows us to simulate the tableting process of rotary tableting machines to a greater extent than when using hydraulical compaction simulators. Thus they will be mainly used in formulation development and scale-up. 

Shah, N. H., Stiel, D., Weiss, M., Infeld, M. H., and Malick, A. W. (1986), Evaluation of two new tablet lubricants—Sodium stearyl fumarate and glyceryl behenate. Measurement of physical parameters (compaction, ejection and residual forces) in the tableting process and the effect of the dissolution rate, Drug Dev. Ind. Pharm., 12(8-9), 1329-1346. 

The tableting process, especially direct compression processes, where there is limited alteration of the raw material prior to compaction, is susceptible to... 

Force measurements made without displacement values are still useful in identifying the dependency of tablet hardness (and other associated characteristics) on compaction force, and also the effect of the tablet press compaction speed on tablet strength (influence of dwell time/effective contact time). Dwell time dependency is an important scale-up factor for the tableting process, and evaluation of the sensitivity of a formulation to dwell time at small scale is useful, although the actual commercial dwell time is not always achievable on instrumented, small-scale tablet presses. 

Schwartz, J.B. Scale-up of the compaction and tableting process. In Pharmaceutical Process Scale-Up Levin, M., Ed. Marcel Dekker New York, 2002. 

---