Compaction tableting process scale

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. 

As shown in Figure 27, it is apparent that when the roller compaction force was scaled-up, the compactibility curve of the tablets shifted downward. Ideally, a formulator would prefer a 60 N hardness window of acceptable force. In this example, the flat part of the curve had no effect on friability and dissolution and thus could be processed. The example does show that for a roller compaction process, a scale-up factor must be considered for the roller compaction force early on in development. Factors that affect the tablet compactibility curve at scale-up include the roller compaction force and strain-rate sensitivity of the compact. 

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). 

Joseph B. Schwartz. 2002. Scale-up of the compaction and tablet protrassfrinHceutical Process Scale-Up, edited by Michael Levine, Marcel and Dekker Publishers, New York, NY, vol. 118, pp. 221-237. 

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. 

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. 

In tableting applications, the process scale-up involves different speeds of production in what is essentially the same unit volume (die cavity in which the compaction takes place). Thus, one of the conditions of the theory of models (similar geometric space) is met. However, there are still kinematic and dynamic parameters that need to be investigated and matched for any process transfer. 

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

The first true compaction simulator capable of mimicking the compaction and ejection cycle of a rotary tablet press was reported by Hunter et al. in the 1970s (2), The evolution of such an instrument presented a novel tool for both powder compression research and scale-up of the tableting process. Celek and Marshall report that although compaction simulators are expensive to purchase, they present the following attributes ... 

Scale-up of the tableting process is a critical step in tablet manufacturing and often causes time consuming operations. Compaction simulators are de.signed to mimic high-speed rotary tablet presses with a minimum quantity of material in the early stage of... 

Production of tablets at medium-to-large scale requires more stringent control of powder properties due to the high-speed compression step. Processing of tablets and the physics of tablet compaction have been the subject of extensive investigation and voluminous literature exists on the topic. 

To address the issue of the scale-up of the tablet compaction process, this chapter will review the following (1) compaction, (2) predictive studies, (3) scale-up/validation process, (4) case studies, and (5) process analytical technologies. 

Stress-strain type equations have been developed for the compaction process, which help provide an understanding of the mechanisms involved in forming a tablet, as well as allowing for the prediction of compaction results. This predictive power of the compaction process is the basis for many scale-up approaches. However, there are compression and consolidation process aspects which are dependent on manufacturing scale, e.g., speed-sensitive materials, and this results in many problems encountered in transferring a technology to production scale. Unfortunately, these scale-sensitive processes have not been as extensively studied, and are less understood. 

Through the use of DOE, a robust formulation and process were developed, resulting in tablets that could be produced at production scale. The compaction profile shifted slightly on scale-up to production, but tablet... 

There are several uses of tablet press instrumentation in the scale-up process itself. One of these involves obtaining a sample of the scale-up batch and compacting that sample on the pilot-plant or research instrumented tablet press on which the formulation has been previously evaluated. Similarity of the fingerprint or the various research plots (Heckel, force-displacement, radial vs. axial plots) is evidence that the scale-up batch is similar to the previously evaluated research batch [2]. 

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