Tablet compacted

Al-Khattat IM, Al-Hassani STS. Towards a computer-aided analysis and design of tablet compaction. Chem Eng Sci 1987 44 707-12. 

The major forces involved in the formation of a tablet compact are illustrated in Fig. 14 (a single-ended model) and are notated as follows FA represents the axial pressure, which is the force applied to the compact by the upper punch, FL is the force translated to the lower punch, and Fr is the force lost to the die wall. If one remembers that for every force there must be an equal and opposite force, the following relationship is obvious ... 

Fig. 14 Forces developed in the formation of a tablet compact., die wall FA, axial pressure applied by upper punch Fd, force lost to die wall Fr, radial die wall , tablet compact.

Figures 15 and 16 provide a summary of the compression cycles for rotary and single-punch tablet presses. The formation of the tablet compact in these two types of presses mainly differs in the compaction mechanism itself, as well as the much greater speeds achieved with rotary type presses. The single punch basically uses a hammering type of motion (i.e., the upper punch moves down while the lower punch remains stationary), while rotary presses make use of an accordion-type compression (i.e., both punches move toward each other). The former find their primary use as an R D tool, whereas the latter, having higher outputs, are used in most production operations.

In order to produce an adequate tablet formulation, certain requirements, such as sufficient mechanical strength and desired drug release profile, must be met. At times this may be a difficult task for the formulator to achieve, due to poor flow and compactibility characteristics of the powdered drug. This is of particular importance when one only has a small amount of active material to work with and cannot afford to make use of trial-and-error methods. The study of the physics of tablet compaction through the use of instrumented tableting machines (ITMs) enables the formulator to systematically evaluate his formula and make any necessary changes. 

ITMs provide a valuable service to all phases of tablet manufacture, from research to production and quality control [109 111]. As a research tool, ITMs allow in-depth study of the mechanism of tablet compaction by measuring the forces that develop during formation, ejection, and detachment of tablets. ITMs can also provide clues about how materials bond,... 

Fig. 18 A typical force-displacement curve. WF= work done overcoming die wall friction WD, work of elastic recovery Wp/, net work involved in tablet compact formation.

Since the viscoelastic properties of the solid undergo a significant change as the solid undergoes a transition from the amorphous to rubbery states (due to elevation of temperature at constant moisture content or to an increase in moisture content at constant temperature), one also expects marked changes in the processing properties of these solids as this transition occurs. Some properties that are likely to be affected include tablet compaction [76], gelatin capsule... 

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. 

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. 

In summary, when tested, the grades of calcium phosphate dibasic discussed above exhibited mechanical properties that were very appropriate for tablet compaction and thus for formulation processing by direct compression, dry granulation, or wet granulation. With this in mind, it is easy to understand the popularity of DCP in pharmaceutical tablet formulations. 

Although this information should have been generated during the development of the formulation, it is often useful to confirm the relationship between these two dependent variables on tablets compacted on the production press during scale-up. Such information becomes invaluable for troubleshooting. 

Wray PE. The physics of tablet compaction revisited. Drug Dev Ind Pharm 1992 18(6 7) 627-658. 

Granulation normally commences after initial dry mixing of the necessary powdered ingredients so that a uniform distribution of each ingredient through the mix is achieved. After granulation the granules either will be packed or may be mixed with other excipients prior to tablet compaction. 

Rodriguez, L., Cini, M., Cavallari, C., Passerini, N., Fabrizio Saettone, M., Fini, A., and Caputo, O. (1998), Evaluation of theophylline tablets compacted by means of novel ultrasound-assisted apparatus, Int. J. Pharm., 170, 201-208. 

Yeh, C., Altaf, S. A., and Hoag, S. W. (1997), Theory of force transducer design optimization for die wall stress measurement during tablet compaction Optimization and validation of split-web die using finite element analysis, Pharm. Res., 14, 1161— 1170. 

The demonstration of the validity of the continuum-based modelling approach to tablet compaction requires familiarity with fundamental concepts of applied mechanics. Under the theory of such a mechanism, powder compaction can be viewed as a forming event during which large irrecoverable deformation takes place as the state of the material changes from loose packing to near full density. Moreover, it is important to define the three components of the elastoplastic constitutive models which arose from the growing theory of plasticity, that is the deformation of materials such as powder within a die ... 

In the manufacturing of tablets, compaction is a very important step, and many factors are involved in affecting the properties of excipients and final products, such as surface structure and wettability of excipients. For formulations, the larger is the surface area of compressible excipients, the greater is the compressibility. ... 

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. " ... 

The general tablet compaction process normally is described by a number of sequential phases rearrangement, deformation (elastic, plastic) of initial particles, fragmentation, and deformation of fragments. Particle-surfaces are brought into close proximity and interparticulate attraction or bonds will be formed. Similar conditions will prevail with the effervescent tablets. 

The surface roughness of the tablet compact and the force of compression used during tableting will affect polymer adhesion, by altering the effective area of contact between the film coating and the surface of the... 

Fig. 15 Influence of triethyl citrate plasticizer concentration on the force-deflection profile of Eudragit L 30 D-55 applied to tablet compacts ( ) 20% plasticizer ( ) 30% plasticizer. (From Ref...

Felton, L.A. McGinity, J.W. Influence of pigment concentration and particle size on adhesion of an acrylic resin copolymer to tablet compacts. Drug Dev. Ind. Pharm. 1999, 25 (5), 599-606. 

Several predictive methods have been applied to the tablet compaction process on a small scale to envisage what will happen on a large scale. Dimensional analysis has been described by Levin as a method of developing functional relationships that describe any given process in a dimensionless form to facilitate modeling and scale-up (or scale down). Although, theoretically, dimensional analysis can be applied to tablet manufacture, no examples are found in the literature. 

Felton LA, McGinity JW. Influence of plasticisers on the adhesive properties of an acrylic resin copolymer to hydrophilic and hydrophobic tablet compacts. Int J Pharm 1997 154(2) 167—178. Okarter TU, Singla K. The effects of plasticisers on the release of metoprolol tartrate from granules coated with a polymethacrylate film. Drug Dev Ind Pharm 2000 26(3) 323—329. 

Powder particle size In high shear mixing In high- ar Particle size distribution Tableting Compaction force and... 

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