Compact process

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... 

Hard shell capsules have often been assumed to have better bioavailability than tablets. Most likely this assumption derives from the fact the gelatin shell rapidly dissolves and ruptures, which affords at least the potential for rapid release of the drug, together with the lack of utilization of a compaction process comparable to tablet compression in filling the capsules. However, capsules can be just as easily malformulated as tablets. A number of cases of bioavailability problems with capsules have been reported [5-8],... 

The effect of machine variables on fill weight and its uniformity were evaluated by Miyake et al. [59] using a Zanasi Z-25. In general, they found that the filling mechanism was a compaction process. The following relationship was found to apply ... 

P York. Crystal engineering and particle design for the powder compaction process. Drug Dev Ind Pharm 18(6-7) 677—721, 1992. 

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. 

While spectral analyzers systems as described above have served their purpose for several decades as process instrumental solutions, today s complex problems and environments necessitate practical and sophisticated sensors or similar compact process instruments. The electronic revolution over the last several decades has resulted in numerous microelectro-optical devices such as cell phones, PDAs and iPods. These... 

If a biodegradable polymer does not exhibit satisfactory film-forming properties, it may also be used as a compression coat requiring a compaction process onto a drug-containing core [62-64]. 

High-energy processes (milling, lyophilisation, granulating, drying) can introduce certain amounts of amorphicity into otherwise highly crystalline material [20]. As has been previously indicated, enhanced levels of amorphicity lead to increased local levels of moismre, and increased chemical reactivity in these areas. Hancock and Zografi [49] reported on the impact of a roller-compaction process on the water vapour sorption of a sample of aspirin. They speculated that... 

T0083 Battelle Pacific Northwest Laboratory, Compact Processing Unit (CPU)... 

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. 

Table 8 Powder Properties from Non-Roller Compacted Formulation and Powder Properties from Vector Freund Lab and Pilot Roller Compaction Processes...

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. 

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... 

The Bib and BI are defined as shown below in Equations (2) and (3), respectively. Both indices describe the bonding ability of the tablets by using the ratio of tensile strength and indentation hardness. However, Bib is determined at low-indentation speed (Hq) and BIw is determined at high speed (Hio). Hence, BI is considered more indicative of actual tableting conditions, whereas Bib relates to slower compactions speeds typical of development or roller compaction processes. 

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. 

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