The compaction process

Many equations have been suggested in the literature to represent the compaction of powders in cylindrical die cavities. A selection of these is given in Table 5.1. There does not appear to be a generally acceptable equation to represent all situations. In rotary high capacity equipment, the situation is further complicated by the influence of such factors as scale of equipment (roll or mill diameter) and the configuration of the compacting surfaces. 

Nomenclature p = pressure applied to compact V = volume of compact at p V0 = volume of compact at zero pressure Vs = solid material volume (void-free) = V/Vs Pa = apparent or bulk density of compact ps = true density of solid material Pr =Pa/Ps my b, alf a2, k, k2 are constants  

Lubricants are often employed to facilitate the uniform transmission of forces and reduce undesirable friction effects during compaction. Lubricants may be classified as internal or external types [2]. Internal lubricants are materials which are added to the particulate feed not only to improve its flow properties (flow into the mold or die and rearrangement during compaction) but also to assist in the release of the final agglomerate from the mold or die. Internal lubricants are generally used in quantities of % to 2%. Internal lubricants, especially when used in excess, may interfere with the optimum cohesion of clean surfaces and reduce the strength of the agglomerates produced. External lubricants are materials used to prevent friction and wear at 

Graphite Stearic acid Magnesium stearate Other metallic stearates Molybdenum disulfide Dry starch Paraffin, waxes 

Materials commonly used as lubricants are listed in Table 5.2. An evaluation of lubricants in various applications has been given in Table 2.4 along with information on a number of binders used in tableting. 

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The surface area of the individual particles themselves changes during the compaction process. Initially, an increase in surface area is noted due to the fracture as compression force increases. Eventually, the surface area decreases due to bonding and consolidation of particles at higher compression forces... 

Several reviews of the mechanisms involved in the compaction process and interpretation of the large amount of data generated from such studies have been... 

The majority of active pharmaceutical agents are administered as tablets, and as a result the characterization of compact species is of great interest to formulators. During the compression step, a variety of particle-particle interactions take place, which ultimately lead to the formation of a stable entity. One may envision that the compaction process results in such consolidation of the input solids that the final density of the tablet approaches the true density of the component materials. 

To illustrate the compaction process that occurs in an extruder, a Maddock solidification [1] experiment (described in detail in Section 10.3.1) was performed using a 63.5 mm diameter machine [2]. The extruder was operated at a screw speed of 60 rpm with a poly(vinylidene chloride) copolymer (PVDC) powder. After the extruder reached a steady-state operation, screw rotation was stopped and full cooling was applied to the extruder. After several hours of cooling, the screw and PVDC resin were removed from the extruder and the density of the bed was measured using Archimedes s principle. The compaction phenomenon in the extruder is shown by the density measurements of the solid bed in Fig. 4.1. As shown in this figure, the density of the solid bed increased from the feedstock bulk density of 0.73 g/cm to nearly the solid density of 1.7 g/cmT... 

As shown In EIgs. 14.10 and 14.15, the cross-sectional views at axial distances less than 10 diameters were similar for both ET and VBET screws. Eor example, the views at 6 diameters were composed of a compacted bed of discrete pellets. The views at 8.4 diameters were In the transition section, where the pellets compacted, softened, and began to melt. For the ET screw, the compaction process had just... 

The structure of the condensed chromatin fiber is still under discussion [1,23,54], with two competing models the original solenoid model of Finch and Klug [16], and the straight-linker model [12,14,55]. Assessing the structure in vivo or in situ has proven impossible thus far, due to technical limitations. Chromatin fibers released from nuclei into solution by nuclease treatment have been widely used as models for fiber structure such fibers are extended at low ionic strength and condensed at ionic strengths believed to be close to those found in vivo ( 150 mM Na" " or 0.35 mM Mg " "). The salt-induced fiber compaction has been extensively studied in the past but is still poorly understood in terms not only of the details of the structure but also in terms of the molecular mechanisms of the compaction process. 

The final density of the compact is less than the maximum packing fraction of the particles, PF ax [cf. Eqs. (4.8) and (4.67)], due to frictional forces at particle contacts that retard particle sliding The effectiveness of the compaction process is quantified... 

Study determined the compact throughput, compact density, and fines (not compacted during vacuum deaeration) when using a new equipment feed system design. The parameters controlled and monitored during the compaction process were vacuum deaeration pressure, roll pressure, roll and screw speeds, room temperature, and humidity. 

The compaction process has been studied extensively and macroscopically and it is well characterized. This is advantageous, since any understanding of the... 

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. 

The compaction process can be described by a variety of force (or pressure)-displacement profiles, such as force versus time, force versus tablet porosity, and force versus tablet properties (hardness, friability, dissolution, etc.). The effect of compaction speed on a variety of tablet properties can also be studied. 

The deformation properties of the drug substance and excipients will have a direct influence on the strength of the tablets that are produced. During the compaction process, as the powder flows from the hopper into the dies, the only force acting on the particles is due to the particles themselves. Then as the punches enter the dies, initially very low pressures are... 

When compared with direct compression results, the dry granulation processes enhance the flow of the powder and decrease the variability of the AUC, the major response. Nevertheless, this variability and the variability of the drug dissolved at 8 h (T7) are greater than the fixed optimal values, particularly for the compaction processes. From the results it is seen that the wet granulation process gave a powder presenting an adequate or better result than the other processes ... 

The pressure applied was sufficient to remove most if not all voids from the compacts. The original protein particles could be thought of as molecular aggregates, not individual molecules. However, the properties of the aggregates themselves needed to be considered since interparticular voids will exist and may also collapse during the compaction process. 

It should be pointed out that these studies were carried out on pure proteins, without the benefit of formulation aids. Additives such as diluents and lubricants would certainly function to reduce the energy applied during the compaction process. However, although suitable for oral use, many orally acceptable diluents are toxic when used parenterally. Thus, the only variable that could be utilized for the compaction of a pure protein might be the residual water level in the protein itself. This information would probably be needed when formulating a compressed pellet for subdermal administration or some other parenteral route. 

As already noted, the most important parameters or characteristics to observe during scale-up of the compaction process are tablet hardness (or tensile strength) and tablet dissolution. However, the following might also provide useful information. 

The size of the obtained granules is also affected by variations of the rotational speed of the plate with respect to a predetermined value (1.12 s ). Increasing the rotational speed of the plate to 1.39 s"1 causes the formation of smaller granules, a disadvantage attributable to the fact that the rolling speed required for obtaining a desired granule size is exceeded. In this case, the compaction process occurs at a faster rate. 

It was Wollaston (30) who in 1829 recognized the great pressures needed for compaction of dry powders—an observation that led to his famous toggle press. Since that time, compaction and deformation of powders and particulate systems have been extensively studied (31-35). There are many difficulties in analyzing the compaction process. Troublesome in particular are the facts that the properties of particulate solids vary greatly with consolidation, and that stress fields can be obtained, in principle, only in... 

Thus, sintering diamond powders with the liquid cobalt present considerably speeds up the compaction process, not changing though the limiting value of shrinkage as compared with the solid phase sintering. 

On the other hand, application of ultrasonic energy results in an increase in the temperature of the die during the compaction process. The consequences of this fact should be taken into account and cannot be neglected in the case of thermola-bile drugs and/or excipients [87,88]. 

Understanding the formulation and compositional effects on the compaction process, including axial loading and unloading along with ejection... 

Because of powder feed variability at the nip and in the roll gap regions, powder leakage is produced during the compaction process. This situation produces excessive fines and possible undesirable processed material. Usually, this problem is caused by uneven powder flow and compact formed when the powder is fed towards the middle of the roll width. Granules produced under these conditions are typically not optimal for further pharmaceutical processing. 

Typically, the compaction process is managed by controlling the input material, the quantity per unit of time, the roll speed, and the roll gap. Allowing the roll gap to float unchecked can influence the production rate and the compact quality. Therefore, it is important to control the compaction process by setting a constant powder feed rate during the compaction operation. 

Polymorphic transformation can take place during pharmaceutical processing, such as particle size reduction, wet granulation, drying, and even during the compaction process.f Tests employed to determine crystal... 

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