Tableting parameters

The key to implementing any corrective actions designed to reduce adverse flow-effects will be using a mathematical two-phase flow analysis to assess the effects on the bulks solids stresses and interstitial gas pressure. This analysis would need to use inputs such as key flow properties (permeability, compressibility) and equipment/process parameters (tableting rate, bin/hopper geometry, and gas pressure gradients) to assess the effect of the potential corrective actions outlined above. 

Figure 4.5. Estimated total analytical cost for one batch of tablets versus the attained confidence interval CI(X). 640 (UV) resp. 336 (HPLC) parameter combinations were investigated (some points overlap on the plot).

Tablets Biological, physicochemical, and structural parameters used to derive QSAR Eq. 19 ...

Measurement of the punch and die forces plus the relative displacement of the punches can provide raw data which, when suitably processed and interpreted, facilitate the evaluation of many tableting parameters. Many of the workers first involved in instrumenting tablet presses concentrated on deriving relationships between the applied force (FA) and the porosity (E) of the consolidating mass. 

Several all-in-one tablet testers are currently available that measure weight, thickness, diameter, and hardness of tablets. In addition these instruments provide digital storage and calculation of statistical parameters and allow for rapid feedback during the tableting process so that the tableting equipment can be adjusted accordingly with minimal downtime. ... 

Within the realm of physical reality, and most important in pharmaceutical systems, the unconstrained optimization problem is almost nonexistent. There are always restrictions that the formulator wishes to place or must place on a system, and in pharmaceuticals, many of these restrictions are in competition. For example, it is unreasonable to assume, as just described, that the hardest tablet possible would also have the lowest compression and ejection forces and the fastest disintegration time and dissolution profile. It is sometimes necessary to trade off properties, that is, to sacrifice one characteristic for another. Thus, the primary objective may not be to optimize absolutely (i.e., a maxima or minima), but to realize an overall pre selected or desired result for each characteristic or parameter. Drug products are often developed by teaching an effective compromise between competing characteristics to achieve the best formulation and process within a given set of restrictions. 

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... 

Wu et al. [46] used the approach of an artificial neural network and applied it to drug release from osmotic pump tablets based on several coating parameters. Gabrielsson et al. [47] applied several different multivariate methods for both screening and optimization applied to the general topic of tablet formulation they included principal component analysis and... 

It becomes evident that a variety of factors need to be considered when designing tablet formulations. In addition, certain compromises between these parameters must be made, because it is nearly impossible to meet all specifications with the same process variables. 

An alternative to the rotating disk method in a quiescent fluid is a stationary disk placed in a rotating fluid. This method, like the rotating disk, is based on fluid mechanics principles and has been studied using benzoic acid dissolving into water [30], Khoury et al. [31] applied the stationary disk method to the study of the mass transport of steroids into dilute polymer solutions. Since this method assumes that the rotating fluid near the disk obeys solid body rotation, the stirring device and the distance of the stirrer from the disk become important considerations when it is used. A similar device was developed by Braun and Parrott [32], who used stationary spherical tablets in a stirred liquid to study the effect of various parameters on the mass transport of benzoic acid. 

SS Kornblum, JO Hirschorn. Dissolution of poorly water-soluble drugs I. Some physical parameters related to method of micronization and tablet manufacture of a quinazolinone compound. J Pharm Sci 59 606-609, 1970. 

A majority of the models incorporate what are essentially curve fitting parameters or functions. Some (C11, K12) are more pertinent to the pressed, briquetted, or tableted beds of particles rather than to granulated ensembles of particles, even though the distinction between the two kinds of pellets is necessarily somewhat arbitrary. 

Fig. 40a, b. NSE spectra of a dilute solution under 0-conditions (PDMS/ d-bromobenzene, T = = 357 K). a S(Q,t)/S(Q,0) vs time t b S(Q,t)/S(Q,0) as a function of the Zimm scaling variable ( t(Q)t)2/3. The solid lines result from fitting the dynamic structure factor of the Zimm model (s. Tablet) simultaneously to all experimental data using T/r s as adjustable parameter. 

Cyclic voltammetry, square-wave voltammetry, and controlled potential electrolysis were used to study the electrochemical oxidation behavior of niclosamide at a glassy carbon electrode. The number of electrons transferred, the wave characteristics, the diffusion coefficient and reversibility of the reactions were investigated. Following optimization of voltammetric parameters, pH, and reproducibility, a linear calibration curve over the range 1 x 10 6 to 1 x 10 4 mol/dm3 niclosamide was achieved. The detection limit was found to be 8 x 10 7 mol/dm3. This voltammetric method was applied for the determination of niclosamide in tablets [33]. 

It is generally agreed that one of the more important parameters of interest to formulators is the flowability of their powdered solids [57,58], The process-ability of these materials is greatly affected by flowability concerns, since the materials invariably need to be moved from place to place. For example when tablets are to be compressed at high speeds, the efficiency of the machine will only be suitable if the powder feed can be delivered at a sufficiently high rate. 

The appearance of tablets and powders during accelerated stability testing can be quantified using tristimulus colorimetry [29]. In this work, various formulations were stored under stress conditions, and the tristimulus parameters... 

Other workers have used the tristimulus parameters to study the kinetics of decomposition reactions. The fading of tablet colorants was shown to follow first-order reaction kinetics, with the source of the illumination energy apparently not affecting the kinetics [49]. The effect of excipients on the discoloration of ascorbic acid in tablet formulations has also been followed through determination of color changes [50]. In this latter work, it was established that lactose and Emdex influenced color changes less than did sorbitol. 

Although UV/VIS diffuse reflectance spectroscopy has not been used extensively in the study of pharmaceutical solids, its applications have been sufficiently numerous that the power of the technique is evident. The full reflectance spectra, or the derived colorimetry parameters, can be very useful in the study of solids that are characterized by color detectable by the human eye. It is evident that questions pertaining to the colorants used for identification purposes in tablet formulations can be fully answered through the use of appropriately designed diffuse reflectance spectral experiments. With the advent of newer, computer-controlled instrumentation, the utility of UV/VIS diffuse reflectance as a characterization tool for solids of pharmaceutical interest should continue to be amply demonstrated. 

The relevant parameters to trigger the release of actives can be the temperature or pH-value of the washing liquor, the salt concentration or even the presence of water. In some automatic dishwashing tablets that have been recently introduced, for instance, the difference in temperature of the main wash cycle and the rinse cycle [89], or the difference in the pH-values of these two stages is utilized to trig-... 

There are no calibrator tablets available for this apparatus. The approach to performance qualification would be as outlined previously, that is, to determine the critical parameters, which in this case will include dip rate and volume control. 

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