Solubility, crystallization-based

Solubility values based on a plateau in the dissolution rate curve, when dissolution of the metastable form is essentially complete and the system reaches a pseudoequilibrium state befori conversion to the stable solid state, are reasonably accurate. Those based on peaks in these curves obtained by Ltting exponential functions to estimate the plateau that might be reached in the absenc< of conversion should only be considered estimates ofthe metastable form solubility. The quantitative gain in these systems may be estimated more accurately by comparing initial dissolution rates for the two forms. In most cases, amorphous form solubilities must be estimated by these techniques due to their rapid crystallization when in contact with solvents. 

These raw materials are mined like rock salt. The potassium chloride is separated by leaching and fractional crystallization based upon the different solubility of individual components of the starting raw material. 

Evaluate the most probable appropriate crystallization method based on solubility, crystallization kinetics, and metastable zone width, if needed. 

Among the first ones to present a complete theoretical approach are Burton, Prim, and Slitcher (1953). The authors developed a mathematical formulation of the problem for metallic systems with partial solid solubility crystallized from the melt in a suspension process. Their theory is based on a boundary layer model and does not account for the mutual dependence of heat and mass transfer but regards the influence of heat transfer as negligible. 

The second important observation on stereoisomer separation also involved ammonium sodium tartrate. Thirty-four years after Pasteur s observation, Jungfleisch (1882) observed that carefully introducing crystals of the individual isomers into different areas of a supersaturated solution of ammonium sodium tartrate resulted in the growth of isomerically pure crystals. These two observations form the basis for most industrial scale crystallizations for the purification of enantiomers or diastereoi-somers. However, it is more common for a solute to crystallize with the thermodynamically stable crystal form being a compound of the two isomers. This is typically denoted as a racemic compound. Secor (1963) made the first systematic review of optical isomer separation by crystallization, based upon phase behavior. Collet, Brienne, and Jacques (1980) applied systematic thermodynamics to the phase behavior, and developed straightforward methods for correlating the solubilities of isomers. 

Many drug substances fall in the category of slightly soluble weak acids, or slightly soluble weak bases, whose salt forms are much more soluble in water. Upon addition of acid to an aqueous solution of a soluble salt of a weak acid, or upon addition of alkali to an aqueous solution of a soluble salt of a weak base, crystals often result. These crystals may be different from those obtained by solvent crystallization of the weak acid or weak base. Nucleation does not necessarily commence as soon as the reactants are mixed, unless the level of supersaturation is high, and the mixing stage may be followed by an appreciable time lag before the first crystals can be detected. Well-formed crystals are more likely to result in these instances than when rapid precipitation occurs. 

K Tl Br-I (KRS-5) 0.500 40.00 20000 250 5796 72 2.37 Toxiq soft crystal deforms under pressure good ATR material, soluble in bases and insoluble in acids, toxic. 

Konno H, Taylor LS (2008) Abdity of different polymers to inhibit the crystallization of amorphous felodipine in the presence of moisture. Pharm Res 25 969-978 Konno H, Handa T, Alonzo DE, Taylor LS (2008) Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine. Eur J Pharm Biopharm 70 493 99 Kostewicz ES, Wunderlich M, Brauns U, Becker R, Bock T, Dressman JB (2(X)4) Predicting the precipitation of poorly soluble weak bases upon entry in the small intestine. J Pharm Pharmacol 56 43-51... 

Strategies to enhance solubility are based on the free energy of solution, which involves not only the crystal lattice interactions, but the interactions between the solutes and the solvent. The two main factors associated with the overall free energy of solution are given by ... 

Equation (11.38) shows that if a CSC exists, there also is a pHmax value associated with that CSC and vice versa. CSC is predicted to increase as ionization increases. Higher levels of ionization increase co-crystal solubility and thus more surfactant is required to achieve the CSC. Equation (11.38) can also be used to engineer the pH ax of a co-crystal based on selection of an appropriate surfactant and concentration. Equations that consider co-crystals with other ionization properties and stoichiometries have been presented elsewhere." " ... 

Methods to determine co-crystal solubility are based on thermodynamic and kinetic approaches. Thermodynamic equilibrium experiments provide a measure of co-crystal solubilization processes, while kinetic studies provide insight about the time scales of dynamic processes and concentration fluctuations during co-crystal dissolution. From equilibrium measurements, we can extract information about the origin of co-crystal solution phase behavior and fine tune solution processes by controlling thermodynamic solubility. We can use the knowledge gained from equilibrium studies to design kinetic studies and separate the thermodynamic and kinetic contributions to the co-crystal dissolution and transformation behavior. 

Also soluble catalyst based on ethene bis(indenyl)zirconium dichloride/methylalu-minoxane can be used [519]. The C-NMR spectroscopically measured isotacticity is in excess of 97%, the molecular weight low (44 000), and the crystallinity 66.9%. Similar to polypropene poly(l-butene) crystallizes in four different modifications [520]. To influence the crystallinity, 1-butene was copolymerized with ethene or propene [521,522] or compounded [523,524]. Poly(l-butene) shows very good stability against stress, corrosion, cracking and is therefore used for pressure tubes. 

The solubility isotherm at 25°C was established and the solid phase compositions were determined by Schreinemakers method. The system is eutonic. The eutonic point is at 8.23 wt% Nd2(Se04)3 and 37.16 wt% Yb2(Se04)3. Solid solutions based on Nd2(Se04)3 5H20 are observed for up to 70.09 mol% Yb2(Se04)3 beyond that mixed crystals based on... 

In the commercial extraction of alkaloids from the drugs in which they exist, the powdered drug, or an alcoholic extract of it, is treated with an alkali such as ammonia or lime to liberate the alkaloid and the alkaloid is then extracted by means of an organic solvent. The crude material thus obtained is purified and finally crystallized either as the base itself or as its water-soluble salts. 

A) Extract the mixture with about 40 ml. of chloroform, in which the free base is very soluble. Run off the lower chloroform layer, dry it with potassium carbonate as in (a), and then add carbon tetrachloride slowly with stirring to the filtered chloroform solution until the base starts to crystallise out. Allow to stand for a short time (t.e., until the deposition of crystals ceases) and then filter at the pump as the crystals lose the last trace of solvent, they tend as before to break up into a fine powder, the deep green colour becoming paler in consequence. 

A small quantity of the base may be recrystallised from hot ether, and magnificent deep green crystals obtained the base is not sufficiently soluble in cold ether, however, to enable this solvent to be used advantageously in the above extractions. 

Add 1 drop (0 05 ml.) of concentrated nitric acid to 2 0 ml. of a 0 5 per cent, aqueous solution of paraperiodic acid (HjIO,) contained in a small test-tube and shake well. Then introduce 1 op or a small crystal of the compound. Shake the mixture for 15 seconds and add 1-2 drops of 5 per cent, aqueous silver nitrate. The immediate production of a white precipitate (silver iodate) constitutes a positive test and indicates that the organic compound has been oxidised by the periodic acid. The test is based upon the fact that silver iodate is sparingly soluble in dilute nitric acid whereas silver periodate is very soluble if too much nitric acid is present, the silver iodate will not precipitate. 

Sulfates. Indium metal and its oxides dissolve in warm sulfuric acid to give a solution of the trisulfate [13464-82-9], In2(S0 2- It is a white, crystalline, deUquescent soHd, readily soluble in water that forms double salts with alkaLi sulfates and some organic substituted ammonium bases. Concentration of the acidified trisulfate solution produces indium acid sulfate crystal [57344-73-7], In(HS0 2> other reaction conditions give basic sulfates. 

Iron(II) hydroxide [18624-44-7], Fe(OH)2, is prepared by precipitation of an iron(II) salt solution by strong base in the absence of air. It occurs as pale green, hexagonal crystals or a white amorphous powder. It is practically insoluble in water, fairly soluble in ammonium salt solutions, and soluble in acids and in concentrated NaOH solution. It is slowly oxidized by air. Conversion to Fe203 atH20 is eventually complete. 

Lead antimonate [13510-89-9] (Naples yellow), Pb2(Sb0 2> mol wt 993.07, d = 6.58g/cm, is an orange-yeUow powder that is insoluble in water and dilute acids, but very slightly soluble in hydrochloric acid. Lead antimonates are modifiers for ferroelectric lead titanates, pigments in oil-base paints, and colorants for glasses and glazes (see Colorants for ceramics). They are made by the reaction of lead nitrate and potassium antimonate solutions, followed by concentration and crystallization. 

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