Tablet properties

Kumar, V., de la Luz Reus-Medina, M. Yang, D. (2002). Preparation, characterization, and tabletting properties of a new cellulose-based pharmaceutical aid. International Journal of Pharmaceutics, Vol. 235,1-2, (March 2002), pp. (129-140), ISSN 0378-5173... 

Tablet Formulations (Immediate Release). Two papers in the mid-1990s reported the earliest studies on immediate release tablets. In the first, tablet formulations of hydrochlorothiazide [33] were modeled in an attempt to maximize tablet strength and select the best lubricant. In the other, a tablet formulation of caffeine was modeled [34] to relate both formulation and processing variables with granule and tablet properties.

Comparative reports in the literature confirm the necessity of employing some calibration procedure if results from testers are to be compared or reduced to actual units of force. This is particularly true where the information is being used to determine relationships between crushing strength to other tablet properties. 

Other applications of the previously described optimization techniques are beginning to appear regularly in the pharmaceutical literature. A literature search in Chemical Abstracts on process optimization in pharmaceuticals yielded 17 articles in the 1990-1993 time-frame. An additional 18 articles were found between 1985 and 1990 for the same narrow subject. This simple literature search indicates a resurgence in the use of optimization techniques in the pharmaceutical industry. In addition, these same techniques have been applied not only to the physical properties of a tablet formulation, but also to the biological properties and the in-vivo performance of the product [30,31]. In addition to the usual tablet properties the authors studied the following pharmacokinetic parameters (a) time of the peak plasma concentration, (b) lag time, (c) absorption rate constant, and (d) elimination rate constant. The graphs in Fig. 15 show that for the drug hydrochlorothiazide, the time of the plasma peak and the absorption rate constant could, indeed, be... 

B. M. Hunter, The effect of the specific surface area of primidone on its tableting properties, J. Pharm. Pharmacol., 26, 58P (1974). 

When the work is carried out on a compaction simulator, it is possible to subject the formulation to high-speed tableting cycles in order to evaluate strain forces in the compacts. This work can be of utmost importance, since it appears that strain rates can exert strong influences on a variety of tablet properties [64]. The information gathered in this way can be used to aid in the transfer of the manufacturing process among different types of instrumentation, and to aid ir the technology transfer process. 

When evaluating the effect of binder concentration on a number of tablet properties, surface area measurements were used to investigate the bond strength of the binder with the other particles [18]. A steady reduction in the surface area of the granules with increasing binder concentration indicated that the binder had covered or penetrated the particles, with the formation of particle-binder bonds. This was related to friability, and the increased bond strength was related to the decreased surface areas. 

The mechanical properties of materials, though not often studied in detail, can have a profound effect on solids processing. Clearly, tableting properties are influenced by the elastic and plastic deformation properties as well as the viscoelastic properties of a material. As we have pointed out, the powder flow properties are also affected, as well as the tendency of materials to set up on storage. Because of the importance of mechanical properties, it is important to be able to... 

TABLE 3 Effect of Disintegrant Incorporation in Granules on Tablet Properties."... 

R Luukkonen, M. Fransson, I.N. Bjorn, J. Hautala, B. Lagerhohn and S. Folestad, Real-time assessment of granule and tablet properties using in-line data from a high-shear granulation process, J. Pharm. Sci., 97(2), 950-959 (2008). 

There are almost always a number of criteria to which the formulation has to fulfil, and in the case of incorporating robustness aspects (as an optimisation criterion) into the optimisation the number of criteria is also increased. It is however almost impossible to fulfil all the criteria in the most optimal way at once. This means that a compromise has to be foimd between all criteria. A large number of methods is available to search for such a compromise variable setting. One of these methods is Pareto Optimality which will be explained and applied in this chapter. Pareto Optimality searches for a compromise between the optimisation of a certain tablet property and the optimisation of the robustness of this property. 

In order to develop physically stable preparations, the effect of tablet composition as well as the effect of storage conditions on the behaviour of physical tablet properties during storage must be studied. 

In the optimization of tablet formulations, different approaches can be used. The one variable at a time method requires many experiments and there is no guarantee that an optimal formulation is achieved. Moreover the interaction between different factors, which may influence the tablet properties, will not be detected [10]. The use of an experimental design can be helpful in the optimization of tablet formulations. Mixture designs can be used to describe the response (tablet properties) as a function of the... 

Many papers have been published in which an experimental design is used to optimize tablet formulations. Both process variables as well as compositional variables (quantitative and qualitative) were used as independent (adjustable) variables. The studied dependent variables (factors to be optimized) are physical tablet properties directly after preparation such as weight variation, crushing strength, dissolution profile, disintegration time and friability. Doombos reviewed papers in which statistical methods were used to optimize tablet formulations [13]. 

Since the aim of this study was to evaluate the use of the change in the tablet properties during storage as a parameter to express the physical stability of tablet formulations, the Storage to Initial Ratio of the crushing strength (SIR(S)) and of the disintegration time (SIR(D)) were calculated and used as response values for equation (2). The calculations of SIR(S) and SIR(D) were performed as in equation (1). The mean of the measurements directly after preparation were used as initial value. 

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. 

These guidelines can be extended to account for other tablet properties. For instance, based on experience gained in divisible tablets, a case can be made to restrict scoring of standard concave, round tablets to diameters of 9 mm and above, whereas flat-faced, round tablets can be successfully scored to diameters of 7 mm and larger. 

Schmidt PC, Rubensdorfer CJW. Evaluation of Ludipress as a multipurpose excipient for direct compression. Part I powder characteristics and tableting properties. Drug Dev Ind Pharm 1994 20 2899-2925. 

Tablet mechanical properties measured on samples prepared on an instrumented tablet press or compaction simulator are an excellent means to characterize excipients under dynamic conditions (8,9). Meaningful data analyses are best achieved if both tablet preparation and tablet property measurements are performed at carefully controlled conditions using standardized procedures. Such testing in the authors ...

Doelker E. Comparative tabletting properties of sixteen microcrystalline celluloses. Drug Dev Ind Pharma 1987 13 1847-1875. 

Lamberson R, Raynor G. Tabletting properties of microcrystalline cellulose. Manufact Chem 1976 47. 

Yromans H, Bolhuis GK, Lerk CF, Kussendrager KD, Bosch H. Studies on tableting properties of lactose. VI. Consolidation and compaction of spray-dried amorphous lactose. Acta Pharmaceutica Suecica 1986 23(4) 231-240. 

Whiteman M, Yarwood RJ. Variations in lactose NF from two different sources and their influence on tablet properties. Drug Dev Ind Pharma 1990 16(11) 1815 1827. 

From these simple data on a single-stroke research press, a formulator can begin to generate relationships between tablet properties and the compressional forces used to compact them. Thus, one could plot tablet hardness as a function of compaction force or pressure (see Fig. 2). The same would be true for disintegration tune, thickness, a dissolution number, etc. In fact, any dependent variable (tablet property) can be related to the independent variable (compaction force.) It is important to remember that force is the parameter one can control and, therefore, the independent variable. 

Compaction force vs. time curves to obtain a peak force on which to base the tablet property relationships and to mcnswe functional dwell time (the time over which the maximum force is applied, most often defined as the time where the compaction force is at 90% of the maximum value)... 

Although there are many tablet properties to be evaluated, the most important to observe during the scale-up process are tablet hardness (or tensile strength) and tablet dissolution. The former could be affected significantly by press speed (if the... 

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