Tablet powder compaction

Yang XS, Lewis RW, Gethin DT, Rowe RC. Modelling of pharmaceutical powder compaction and tableting effect of particle sizes and irregular shape. Powder Technol. 2005 in press. 

Studies involving instrumented compaction equipment can be extremely useful in the development of dosage forms, especially when the amount of drug substance is limited in quantity. Marshall has described a program in which dynamic studies of powder compaction can be used at all stages of the development process to acquire formulation information [63]. The initial experiments include a determination of the intrinsic compactability of the compound. In subsequent work, simple tablets are prepared, and tested for dissolution, potency, and content uniformity. Through studies of the compaction mechanism, it becomes possible to deduce means to improve the formulation under study. 

To demonstrate the ability to evaluate intersample variations, an over-the-counter (OTC) pain relief medication from two different manufacturers was compared. The samples contain three APIs each acetaminophen, aspirin and caffeine. Pure acetaminophen, aspirin and caffeine samples are obtained in either tablet form or powder compact and included within the same FOV as the tablets to provide simultaneous reference materials for the tablet samples. The tablets and pure components were arranged as shown in Plate 8.1a. Measurements on all samples were collected simultaneously. Tablet A samples from one manufacturer have a reported label concentration of 37%, 37%, and 10%, for the three API components, respectively. Tablet B samples from the second manufacturer contain the same three APIs, at label concentrations of 39%, 39%, and 10 %, respectively. In addition to these samples, tablet C samples are included in the array of tablets. These samples contain only acetaminophen as the API with a reported label concentration of 79%, and are made by the manufacturer who produces tablet A. The remaining mass of all three tablet types represents the excipient (binder, disintegrant, and lubricant) materials. 

The concentrations of the active ingredients as reported from the manufacturer s label are 37% acetaminophen, 37% aspirin, and 10 % caffeine. The remainder of the tablet mass represents the excipient (binder, disintegrant, and lubricant) materials. Pure acetaminophen, aspirin and caffeine samples are obtained in either tablet form or powder compact and used to obtain reference specua of pure components. 

Oral tablets and Powder compacts, or fills in gelatin capsules, that capsules are swallowed. Must be easy to swallow... 

The use of compaction simulators was first reported in 1976. Since then, a variety of simulators have been developed. Hydraulic simulators, as well as mechanical simulators, are available to characterize raw materials, drug substances, and formulations, as well as to predict material behavior on scale-up. The appeal of simulators is due to the fact that they purport to provide the same compaction profile as experienced on a tablet press while using only gram or even milligram quantities of powders. Compaction simulators can achieve high speeds, as would be experienced on a production tablet press, and can be instrumented to measure a variety of parameters, including upper and lower punch force, upper and lower punch displacement, ejection force, radial die wall force, take-off force, etc. Summaries on the uses of simulators and tablet press instrumentation can be found in (19,20). 

Tablets or compacted powders and granules are widely utilized for the oral delivery of drugs. In addition, tablets may also be used for delivery to other body sites such as the vagina or as sterile implants.

Intuitively, SF is a measure of the degree of compression because it increases with applied pressure. Mechanical properties of powder compacts are dependent on SF and best compared at the same SF. The authors laboratory selected 0.85 SF as its standard because it approximates the midpoint of the range typical of immediate release tablets (0.8-0.9). 

The tableting indices methods, summarized in Table 1, require powder compacts that are prepared under carefully controlled conditions so that they are essentially free of flaws (4,7). These compacts are the samples used for indentation hardness and TS measurements. 

A powder compact s TS is the stress required to separate its constituent particles in tensile mode. This is measured for the tableting indices by transverse compression of the square compacts, using narrow platens. Stresses build within the sample until it fails in a tensile mode that is perpendicular to the direction of platen movement. Tablets that are manufactured on a traditional tablet press and that have high TS are considered hard and generally robust, and so this is a highly desired attribute for immediate release and other tablet types. 

To demonstrate the ability to evaluate inter-sample variations, tablet groups from two different manufacturers in an over-the-counter (OTC) pain relief medication were compared. Pure acetaminophen, aspirin, and caffeine samples are obtained in either tablet form or powder compact and included within the same FOV as the tablets to provide simultaneous reference materials for the tablet samples. The tablets and pure components were arranged as shown in Plate la. This FOV contains 20 tablets and the... 

In a demonstration of the pharmaceutical advantage that can be realized through the use of a cocrystal form of a substance, it was shown that the 1 1 cocrystal of caffeine and methyl gallate exhibited significantly improved powder compaction properties [64], The compression characteristics of the cocrystal were reported to be excellent over the entire pressure range studied, with the tablet tensile strength of the cocrystal being twice that of caffeine at pressures less than 200 MPa. The superior compaction properties of the cocrystal product were attributed to the presence of slip planes in crystal structure. 

Pressure methods Unidirectional compaction 1. Powders compressed within die cavity into cylindrical or other simple shapes by action of punch. Tableting, powder pressing, dry pressing, hot pressing Tablet machines, powder presses. 

Oates, R. J., and Mitchell, A. G. (1989), Calculation of punch displacement and work of powder compaction on a rotary tablet press,/. Pharm. Pharmacol., 41, 517-523. 

Imbert, C.,Tchoreloff, P., Leclerc, B., and Couarraze, G. (1997), Indices of tableting performance and application of percolation theory to powder compaction, Eur. J. Pharm. Biopharm., 44, 273-282. 

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 ... 

Mannitol Freely soluble, used particularly for chewable tablet powder form has poor flow and compaction granular form has good flow... 

During compression, the powder compact typically undergoes a temperature increase, which depends on frictional effects that are dependent, in turn, on the specific material characteristics, the lubrication efficiency, the magnitude and rate of application of the compression forces, and the machine speed. Typical temperature increases are between 4 and As the tablet tem-... 

Oates, R.J. Mitchell, A.G. A new method of estimating volume during powder compaction and the work of compaction on a rotary tablet press from measurements of apphed vertical force. J. Pharm. Pharmacol. 1993, 46, 270-275. 

The possibility of determining eutectic temperatures of multicomponent mixtures has practical value in another respect. During tableting, for example, heat is generated in the punch and die and in the powder compact measurement of the eutectic temperature can give information on whether this rise in temperature is likely to cause problems of melting and fusion. 

Table 70. Ascorbic acid tablets from compacted powder with povidone K 30 [367]...

Stress transmission in powders controls flow out of hoppers, feeders, filling of tubes, and compaction problems such as tableting and roll pressing. (See Powder Compaction. )... 

FIG. 21-141 Density developed in one-half of a tablet during compression, based on plasticity and compaction models. Lewis et al. Casting and Powder Compaction Group, Department of Mechanical Engineering, University of Wales Swansea, http //www.swan.ac.uk/nfa/, with permission.)... 

H. S. Thacker and E. Forster, High speed tabletting, in Compaction 73 (ed. A. S. Goldberg), Proceedings of First International Conference on Compaction and Consolidation of Particulate Matter, Powder Technology Publication Series No. 4, Powder Advisory Centre, London, UK, 1972, pp. 183-90. 

The manufacture of tablets, and to a lesser extent powder-filled hard gelatin capsules, involves the process of powder compaction, the purpose of which is to convert a loose incoherent mass of powder into a single solid object. Knowledge of the behaviour of powders under pressure, and the way in which bonds are formed between particles, is essential for the rational design of formulations. 

Table 3 shows that Avicel PH 102 and PH302 formed powder compacts with similar relatively high dynamic indentation hardness, whereas that of Avicel PH 105 was considerably lower, indicating PH 105 was the most ductile of the three compacted materials. Relative to other excipients, the values for these materials were fairly low, indicating greater ductility. Ductility is a desirable trait that promotes bonding and strength in tablets. 

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