Scale tableting

In an effort to overcome the dwell time/scale-up issues. Metropolitan Computer Corporation (MCC) has developed a single-station development tablet press that reproduces the compaction event time of manufacturing-scale tablet presses. The Presster (see Fig. 6) can be set up to match the rate, roll wheel configuration, and tooling of any manufacturing-scale tablet press. This enables the formu-lator to eliminate compaction rate as a variable upon scale-up. It does require that early in development the formulation scientist identify the tablet press that the commercialized product will run on. This is in keeping with the theme of this chapter—begin a development project with the end in mind. 

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. 

Nqvist, H. Measurement of flow properties in large scale tablet production. Int. J. Pharm. Tech. Prod. Mfr. 1984, 5 (3), 21-24. 

A tablet containing two drug compounds, A and B, is being scaled up from kilogram to half-ton batches in preparation for a regulatory submission. The applicable specifications and sample work-up methods are... 

There are a number of industrial and technological areas in which nanoscale adhesion is important. One of the earliest fields concerned with adhesion on this scale was colloid science. Colloid particles lie in the intermediate region between macro and nano, with dimensions typically of the order of hundreds of nanometers up to a few microns. This means that their true contact areas he well within the nano-domain and are influenced by interactions on this length scale. Adhesion between such particles is important, due to its influence on mineral separation processes and on the aggregation of powders, for example, on the walls of machinery or in the forming of medical tablets. In an extraterrestrial context, such... 

Fig. 40a, b. NSE spectra of a dilute solution under 0-conditions (PDMS/ d-bromobenzene, T = = 357 K). a S(Q,t)/S(Q,0) vs time t b S(Q,t)/S(Q,0) as a function of the Zimm scaling variable ( t(Q)t)2/3. The solid lines result from fitting the dynamic structure factor of the Zimm model (s. Tablet) simultaneously to all experimental data using T/r s as adjustable parameter. 

Raman spectroscopy is emerging as a powerful analytical tool in the pharmaceutical industry, both in PAT and in qualitative and quantitative analyses of pharmaceuticals. Reviews of analyses of pharmaceuticals by Raman spectroscopy have been published.158 159 Applications include identification of raw materials, quantification of APIs in different formulations, polymorphic screening, and support of chemical development process scale-up. Recently published applications of Raman spectroscopy in high-throughput pharmaceutical analyses include determination of APIs in pharmaceutical liquids,160,161 suspensions,162 163 ointments,164 gel and patch formulations,165 and tablets and capsules.166-172... 

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. 

Tablets, powder- and liquid-filled capsules Microbial limit test, TAMC, TCYMC only Test development, scale-up and validation batches only 0, 6, 12, 24, 36 months...

Figure 7.4 Collection of commercial Raman probes designed for different installations (a) laboratory scale probe with interchangeable immersion or noncontact optics, shown with immersion option (b) probe shown in (a) installed in laboratory fermentation reactor (c) production scale immersion probe (d) probe shown in (c) installed in a glass reactor (e) gas phase probe with flow through cell (f) probe shown in (e) installed in process piping (g) wide area illumination (WAI) noncontact probe after completion of a pharmaceutical tablet coating operation. Adapted, with permission. Copyright 2004 Kaiser Optical Systems, Inc.

Figure 8.16 Analysis of selected areas of the best laboratory blend (Tablet E) and the commercial blend (tablet F). (a) Truncated PLS score imaged for the API component (depicted as white) from the central region of the tablets showing that on a local scale, the blending in both samples is uniform and (b) histograms and resulting %SD of the distribution from the truncated images. Note that both examples display nearly normal distributions.

The evolution and optimisation of a formulation is an experimental stage that will be conducted on small batches of the material. For a drug with a tablet weight of 250 mg, test batches would t)rpically be 0.5-1 kg, providing up to 4000 tablets for analysis, performance testing and initial stability studies. Similar scales will be used in the optimisation of the product s packaging. 

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