Solubility based calculations

A method for the estimation of the total alkaloids and of non-phenolic alkaloids (emetine fraction) is given in the British Pharmacopoeia, 1932, Addendum VI, which requires the drug to contain not less than 2 per cent, of alkaloids, of which at least 55 per cent, must be non-phenolic bases, calculated as emetine. The British Pharmacopoeia also gives an assay process for emetine in emetine bismuth iodide, the form in which the drug is chiefly used in medicine it is required to contain not less than 25 and not more than 28 per cent, of emetine. In the United States Pharmacopoeia, XIII, both Cephcelis Ipecacuanha and C. acuminata are recognised and must contain not less than 2 per cent, of ether-soluble alkaloids. 

In silico models should also be used with care when it comes to predicting the absorption properties of salts and bases with low solubility in the intestinal fluids. All models use the thermodynamic solubility to calculate the dissolution rate and the saturation solubility in the different parts in the GI tract. However,... 

Product Workup Procedures, A sample of the products was continuously extracted with THF and then with pyridine. Pyridine insolubles were analyzed for ash and conversions of MAF coal to pyridine solubles were calculated on the basis of the ash analyses and the mass recoveries. A mass recovery balance was calculated for each experiment. The mass recoveries averaged 97.8 percent. The mass and ash based conversions diverged by an average of only 2.7 percent. 

Published reports discussing the influence of calcium carbonate solid surfaces on the phosphate ion concentration in natural water (2, 3) include 1)solubility product-based calculations 5) iTspontaneous precipitation experimehts from highly supersaturated solutions 7j 9) 3) adsorption of phosphate onto calcium carbonate (10, 11, 12, 13), These experiments have provided useful information, but several have not included activity coefficient or ion pair corrections in their analyses, seriously limiting the applicability of the results. 

The following example illustrates how solubility-product calculations are used to determine the feasibility of separations based on solubility differences. 

Solubility product calculations are actually based on heterogeneous equilibria. Why are pure soUds and liquids exempted from these calculations ... 

Problem Calcium hydroxide (slaked lime) is a major component of mortar, plaster, and cement, and solutions of Ca(OH)2 are used in industry as a cheap, strong base. Calculate the solubility of Ca(OH)2 in water if the fC p is 6.5X10 . 

Figure A-35 Solubility of Th02(am, hyd) under 0.1 and 1.0 bar C02(g) in 0.5 M NaC104 [19940ST/BRU]. The calculations are based on the equilibrium constants and SIT coefficients selected in the present review and the solubility constant calculated from the data in carbonate-free solutions, logi A ° = -(48.0 + 0.5). The dotted curves are calculated with the equilibrium constants proposed by Osthols et al. for Th(OH)4(aq) and Th(0H)3(C03) (designated here as Th (OH)4 ,(aq) and Th ,(OH)4 i(C03) ).

METHODS OF CALCULATION OF SOLUBILITY BASED ON THERMODYNAMIC PRINCIPLES... 

An important first step in any model-based calculation procedure is the analysis and type of data used. Here, the accuracy and reliability of the measured data sets to be used in regression of model parameters is a very important issue. It is clear that reliable parameters for any model cannot be obtained from low-quality or inconsistent data. However, for many published experimentally measured solid solubility data, information on measurement uncertainties or quality estimates are unavailable. Also, pure component temperature limits and the excess GE models typically used for nonideality in vapor-liquid equilibrium (VLE) may not be rehable for SEE (or solid solubility). To address this situation, an alternative set of consistency tests [3] have been developed, including a new approach for modehng dilute solution SEE, which combines solute infinite dilution activity coefficients in the hquid phase with a theoretically based term to account for the nonideality for dilute solutions relative to infinite dilution. This model has been found to give noticeably better descriptions of experimental data than traditional thermodynamic models (nonrandom two liquid (NRTE) [4], UNIQUAC [5], and original UNIversal Eunctional group Activity Coefficient (UNIEAC) [6]) for the studied systems. 

The application of SolventPro with NRTL-SAC and the PC-SAFT models for solubility predictions, multi-level property estimation and solution of some common solvent-based calculations needed in pharmaceutical industry have been demonstrated using selected case studies. The NRTL-SAC model in combination with the UNISAC model and a GC version of the PC-SAFT have shown great potential in the calculation of solid solubility data. A comprehensive database of pure component data (or their reliable predicted values), however, is necessary for predictions of solid solubility for a wide range of chemical systems needed by the pharmaceutical industry. The option available in SolventPro is a very good start. 

If Stober s views are correct and cristobalite, for example, has no true equilibrium solubility, then calculations based on published solubility cannot be valid. The need for a more accurate definition of solubility has been pointed out by. Weill and Bot-tinga (146). Data presented as solubility of different forms of silica is often only an indication of the rate of solution or the limiting concentration reached under particular conditions. Thus a report that opal is 15-18 times as soluble as anhydrous silica at pH 12.8 merely indicates the relative rate of dissolution (147). 

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