Dissolution experiments

It is advantageous with a new drug substance to be able to estimate what its solubility will be prior to carrying out dissolution experiments. There are several systems of solubility prediction, most notably those published by Amidon and Yalkowsky [14-16] in the 1970s. Their equation for solubility of p-aminobenzo-ates in polar and mixed solvents is a simplified two-dimensional analog of the Scatchard-Hildebrand equation and is based on the product of the interfacial tension and the molecular surface area of the hydrocarbon portion of a molecule. 

Quite often a compound is rather unstable in aqueous solution. Hence the long exposure to liquid required for traditional solubility measurements will cause decomposition, and the resulting solubility results will be unreliable. In this particular case a method known as Nogami s method may be used. If a solution experiment is carried out as a dissolution experiment with samples taken at equal time intervals, 8, it can be shown [20] that when the amount dissolved at time t + 8 is plotted versus the amount dissolved at time t, a straight... 

Table 1 lists experimental results from HPWH s original paper [2] in which the dissolution of benzoic acid tablets in aqueous sodium hydroxide solutions was measured gravimetrically. Results from other dissolution experiments in acetate, phosphate, carbonate, and tetraborate buffers, where agreement between theory and experiment were comparable to those listed in Table 1, established this paper and the theoretical HPWH model as the premier reference for dissolution with reaction in pharmaceutics in the 1960s and throughout the 1970s. 

Also, hydrates are more soluble in water-miscible solvents than are the corresponding anhydrous forms. For example, the solubility of caffeine hydrate is lower than that of anhydrous caffeine in water but higher in ethanol. The maximum concentration seen may be due to the solubility of the anhydrous crystalline phase or due to a temporary steady state in which the rate of dissolution of the metastable anhydrous form and the rate of crystallization of the stable hydrate are equal. The decreasing concentration represents crystallization of the stable hydrate from a solution supersaturated with respect to it. If the maximum concentration of the solute in the dissolution experiment corresponds to the solubility, then the initial increase in concentration follows the Noyes-Whitney equation [15]. Van t Hoff plots of log solubility versus the reciprocal of temperature give linear relationships (Fig. 16). 

The steady-state dissolution rate of chrysotile in 0.1m NaCI solutions was measured at 22°C and pH ranging from 2 to 8. Dissolution experiments were performed in a continuously stirred flowthrough reactor with the input solutions pre-equilibrated with atmospheric concentrations of C02. Both magnesium and silicon steady-state fluxes from the chrysotile surface were regressed and the following empirical relationships were obtained ... 

Hproblems associated with all the trihalides of this review of the presence of small amounts of hydrates or oxochlorides. While on the matter of possible impurities, it may be recalled that in Bommer and Hohmann s early work there is a discrepancy between enthalpies of solution of anhydrous trichlorides and of respective metals in hydrochloric acid. Here the more likely impurity to be responsible is unreacted potassium metal in the lanthanide metal used in the hydrochloric acid dissolution experiments. 

Schematic representation of concentration in solution, C, as a function of distance from the surface of the dissolving mineral. In the lower part of the figure, the change in concentration (e.g., in a batch dissolution experiment) is given as a function of time.

Another source of divergence is the use of different models for the aqueous carbonate systems. Precipitation and dissolution experiments can be carried out in closed or open systems and various ways of pH-adjustments (see 8.2). 

One additional aspect of laboratory dissolution experiments is the question of stoichiometric vs. non-stoichiometric dissolution. Many of the studies cited above analyzed only a few of the elements released by feldspar that is, although alkalis, alkaline earths, silica, and aluminum may be released during dissolution of feldspar, few studies report analyses for all elements. Often, only silica was analyzed. Where multiple elements are analyzed, they are often released to the solution in proportions which do not correspond to the bulk stoichiometry of the feldspar ( ] ). 

The temperature influences the drug s saturation solubility and also affects the kinematic viscosity (density of the liquid ) as well as the diffusion coefficient. Therefore, when performing dissolution experiments, temperature should be monitored carefully or preferably kept constant. 

Figure 10 Rotational (tangential) flow (UA) as a function of stirring rate (co) for paddle (filled circles) and basket (open circles) Mean SD position S2 approximately 1 cm above the paddle and midway between the paddle shaft and the wall of the dissolution vessel. (Please note that, in contrast to simulation techniques such as, for instance, computational fluid dynamics, these data are based on dissolution experiments.) Source Data from Ref. 10, UPE method.

In the paddle method, bulk Reynolds numbers range from Re = 2292 (25 rpm, 900 mL) up to Re = 31025 (200 rpm, 500 mL). In contrast, Reynolds numbers employing the basket apparatus range from Re = 231 to Re = 4541. These Reynolds numbers are derived from dissolution experiments in which oxygen was the solute [(10), Chapter 13.4.8] and illustrate that turbulent flow patterns may occur within the bulk medium, namely for flow close to the liquid surface of the dissolution medium. The numbers are valid provided that the whole liquid surface rotates. According to Levich (9), the onset of turbulent bulk flow under these conditions can then be assumed at Re 1500. 

The effect of thr and allothr on the racemic crystals of ser is further manifested independently by dissolution experiments. When rhomblike crystals of ser grown in the presence of (/ ,S)-thr are dissolved in the presence of (fl)-thr, well-formed etch pits develop only at the (011) and (Oil) faces. By virtue of symmetry, similar etch pits form only at the (011) and (Oil) faces when (S)-thr is present... 

This section considers aspects and examples of the dissolution behaviour of individual iron oxides. Additional data are listed in Table 12.3 for a range of experimental conditions. As yet, characteristic dissolution rates carmot be assigned to the various iron oxides (Blesa Maroto, 1986). There are, however, some consistent differences between oxides with considerable stability differences, hence a comparison of the oxides is included here. In addition, the reactivity of any particular oxide may vary from sample to sample, depending on its source (natural or synthetic) and the conditions under which it formed. To illustrate this. Table 12.4 summarizes conditions and results from dissolution experiments in which a range of samples of the same oxide was compared. How the properties of the sample influence its dissolution behaviour is still not fully understood. A thorough characterization of the samples by solid state analysis, e. g. by EXAFS, to provide a basis for understanding the dissolution behaviour is, therefore, desirable. 

Tab. 12.4 Conditions and results from dissolution experiments comparing a range of samples of the same oxide... 

Zhang (1993) used this approach successfully to model concentration profiles from crystal dissolution experiments. The applicability needs to be investigated further. To establish this method, a major effort is necessary to extract and compile V values for geological applications. 

Although diffusive crystal dissolution is seldom encountered in nature, its theoretical development is instructive for understanding convective crystal dissolution, and it is often encountered in experimental studies. Such experiments are easy to conduct, and can be applied to infer diffusion coefficients, to establish equilibrium conditions, and to investigate the rate of diffusive crystal dissolution. Furthermore, the interface-melt composition and diffusivity obtained from diffusive crystal dissolution experiments are of use to estimate convective crystal dissolution rates (Section 4.2.3). 

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