Compression profile

Compression force/hardness profile The compression/hardness profile of a granule batch is an important property. Different subunits of two formulations were selected and compressed using different compression forces in order to obtain tablets. The tablets were tested for hardness as a function of different subrmit numbers (Figs. 11,12). From experience, it is well known that certain formulations show an excellent compression profile as small batches but do not keep this property on the batch size increasing. This is another advantage of the quasi-continuous production concept as, in principle, the quality of the small batch is not changed by the repetitive procedure. 

Figure 4 Comparison of a production compression profile (Courtoy RlOO/36 stations) to a Presster compression profile simulation.

In Figure 6, if you compare the compression profiles of the drug substance from the two sites, the new material is actually forming stronger compacts than the original material. 

Below is an example of pilot work in support of a scale-up to production. In this example, the final blend was compressed on a 16 station rotary Beta press using ovaloid tooling. A compression profile, as shown in Figure 9, was generated. The speed of the tablet press was fixed at 78 rpm. Forces ranging from 8 to 28 kN were evaluated. Lamination was observed at forces greater than 25 kN. The curve was relatively flat between 15 and 25 kN forces with hardness ranging from 175 to 215 N. 

Figure 2S Compression profiles of tablet cores made from ribbons compacted at three different forces.

Figure 28 Dependence of the compression profiles of bilayered tablets on size.

The first component, which expresses the curve shape, exhibits an opposition of the release profiles obtained by wet granulation and by direct compression. The wet granulation profile has a sigmoid aspect while the direct compression profiles, particularly those for the tablets obtained in rotary machine, are nearly linear. 

In the plot of the first components (Fig. 5), the difference between the wet granulation and the direct compression profiles is confirmed. The first component discriminates between the shape profiles. The second component discriminates between the initial slopes of the release profiles. Then, it is possible to differentiate between the separate compaction and the other processes, because it has the highest initial slope. This is also observed in Fig. 3. 

Coprocessed excipients have been mainly used in DC tableting because of their better flow ability and compressibility, and the excipient formed is a filler-binder. The compressibility of several coprocessed excipients such as Cellactose (45), SMCC (42,44), and Ludipress (BASF AG, Ludwigshafen, Germany) (46) have been reported to be superior to the physical mixtures of their constituent excipients. While comparing the compressibility profile of SMCC with MCC in the presence of high compression forces, the former was found to retain the compaction properties,... 

Compression speed The formulation should be compressed at a wide range of compression speeds to determine the operating range of the compressor. The adequacy of the material s flow into the dies will be determined by examining the tablet weights. Is a force feeder required to ensure that sufficient material is fed into the dies Compression/ejection force The compression profile for the tablet formulation will need to be determined to establish the optimal compression force to obtain the desired tablet hardness. The particle size/size distribution or level of lubricant may need to be adjusted in order to have a robust process on a high-speed compressor. 

Agitating bar (on/off pattern) Compression profile in lubrication step... 

Postgranulation mix time Uniformity of dosage unit Compression profile Dissolution profile... 

Roll pressure Auger screw rate Roller surface type Compression profile... 

TABLE 6.17 Effect of Tableting Speed on Compression Profile for Drug A Formulation... 

Figure 2 illustrates the difference in compression profiles of the upper and lower punches and the punch movement with fictitious rotary and eccentric presses. 

FIGURE 2 Punch movements and compression profiles of upper and lower punches of... 

Instrumented tablet presses with computer interfaces allow the pharmaceutical scientist to study the mechanism of compaction and the relationship of the mechanism to tablet-compaction properties and formulations. In addition, automated systems are useful to develop compression profiles for reference purposes, to control weight of tablets during development and production, and to monitor punch wear. This automation reduces the burden on personnel faced with the requirements of quality control. Merck Sharp and Dohme s major production facility in the United Kingdom is fully computerized to manufacture a high-volume tablet product as well as multiple-tablet products. " ... 

In a similar, yet more extensive study, the compaction of compressible sugar was examined for materials preconditioned at different relative humidities. The hardness versus compression profiles (Fig. 21) for these samples show a group of lines whose slope appears to be a function of moisture content. This relationship is also demonstrated in Fig. 22, where the slope is used as a compressibility index. This index is a linear function of moisture content samples with desorbed moisture did not differ from those with adsorbed moisture. 

Fig. 14 shows a typical set of upper and lower compression profiles. One can see that the lower trace is smaller than the upper. On a single station press, only the upper punch is usually moving, and the difference is caused, mainly, by the friction of the compressed powder inside the die. 

The simulation can be achieved by one of the two procedures matching either the force (load control) or the movement of punches (position control) at any given moment of time. Thus, when running a simulator, one has a choice to mimic the force/time path (compression profile) or the motion of the punches (punch displacement curves). It is impossible to mimic both at the same time on any hydraulic compaction simulator. 

The compression profile (force vs. time) is impossible to calculate theoretically because it has a different shape for different materials and tooling. 

As a high-speed single station press, mechanical compaction simulator will be able to plot compressibility profiles, Heckel graphs, calculate work of compaction, and virtually any other imaginable variable that is of interest to formulators. Tensile strength of tablets made on a Betapress and The Presster was similar. ... 

FIGURE 33 Compressibility profiles for pre-gelatinixed starch at different tableting speeds. Source Adapted from Ref. 52. 

Two examples follow. First, let the transverse compression vary harmonically along m then the constrictive strain rate also varies harmonically. Where is a maximum, d a Jdx is also a maximum and the two contributions to reinforce each other both vary harmonically and are in phase. Second, let the sample consist of two polymorphs of different viscosities as in Chapter 13 then a uniform constrictive strain rate leads to nonuniform transverse compression. Profiles of are exponential in such a way that where (t is less than its remote value, d a Jdx is greater than its remote value. The two contributions to e vary antipathetically and can add up to a constant sum at all points along the cylindroid axis x. ... 

Requires extending the holding time at the peak temperature under pressure. Table 6.36. Compression Profile of Fluoropolymers... 

Gradient compression stockings have been used for the treatment of chronic venous insufficiency. The function is realized in sportswear and socks with elastomeric fiber for the required compression profile and elasticity for perfect fit and functionality. This graduated compression is to improve blood circulation and reduce muscle... 

Following the preceding section, relevant engineering properties of interest i.e. strength and stiff-ness/compressibility profile and in some eases the permeability profile may be selected at this... 

The maximum rate of compression, as shown by DTMA, is observed at 191 0. However, when a sample which was preheated to 290 0 was run in the same fashion (Figure 10), a multi-stage compression profile is observed by the DTMA thermal curve. This effect was very reproducible. 

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