Solubility saturation

H BO is kept at near-saturation solubility varies direcdy with temperature. 

Self regulating chromium The self-regulating chromium solutions were introduced to eliminate the need for maintaining the correct catalyst concentration by periodic analysis they depend on the addition of a sparingly soluble sulphate to the bath which supplies the correct amount of SO 4 automatically. Initially strontium sulphate (solubility approx. l-75g/l at 30°C and 21 g/1 at 40°C) was employed for this purpose. The strontium sulphate forms a layer on the bottom of the bath, which must be stirred from, time to time. A bath with a CrO, concentration of 250 g/1 would have a catalyst content of l 52g/l SrS04 and 4-35 g/1 of KjSiF. Potassium dichromate and strontium chromate have also found application as additives for the control of the saturation solubility of the catalyst. 

Just as the saturated solubility of sugar in water is limited, so the solid solubility of element B in metal A may also be limited, or may even be so low as to be negligible, as for example with lead in iron or carbon in aluminium. There is extensive interstitial solid solubility only when the solvent metal is a transition element and when the diameter of the solute atoms is < 0 6 of the diameter of the solvent atom. The Hume-Rothery rules state that there is extensive substitutional solid solubility of B in >1 only if ... 

Table 21.22 Saturated solubilities of atmospheric gases in sea-water at various temperatures Concentrations of oxygen, nitrogen and carbon dioxide in equilibrium with 1 atm (lOI 325 N m ) of designated gas...

The next term in Eq. (1) that can be manipulated is Cs, the saturation solubility of the drug. This variable can be influenced by both patient and pharmaceutical variables. The patient variables include the changes in PH as well as the amounts and types of secretions along the GIT. Additionally, both the physical and chemical properties of a drug molecule can be modified to increase or decrease its saturation solubility. 

Another variable that influences the saturation solubility of a drug molecule is its degree of solvation. Since the anhydrous, hydrated, and alcoholated forms of a drug have slightly different solubilities, they may well have different dissolution rates and, therefore, different rates of absorption. However, these differences may not be clinically significant [35],... 

Q = saturation solubility of drug (macroparticles) y = interfacial tension between drug particles and the solubilizing fluids M = Molecular weight of the drug r = radius of the microscopic drug particle R = ideal gas constant... 

Fig. 6 Solubility effects on drug stability curve A, drug formulated as lOmg/mL solution (q/2 = 1 year) curve B, drug formulated as a suspension with a saturated solubility of 1 mg/mL (ti/2 = 7.3 years). 

The side-by-side diffusion cell has also been calibrated for drug delivery mass transport studies using polymeric membranes [12], The mass transport coefficient, D/h, was evaluated with diffusion data for benzoic acid in aqueous solutions of polyethylene glycol 400 at 37°C. By varying the polyethylene glycol 400 content incrementally from 0 to 40%, the kinematic viscosity of the diffusion medium, saturation solubility for benzoic acid, and diffusivity of benzoic acid could be varied. The resulting mass transport coefficients, D/h, were correlated with the Sherwood number (Sh), Reynolds number (Re), and Schmidt number (Sc) according to the relationships... 

The boundary conditions for this early dissolution model included saturated solubility for HA at the solid surface (Cha ) with sink conditions for both HA and A at the outer boundary of a stagnant film (Cha = Ca = 0). Since diffusion is the sole mechanism for mass transfer considered and the process occurs within a hypothesized stagnant film, these types of models are colloquially referred to as film models. Applying the simplifying assumption that the base concentration at the solid surface is negligible relative to the base concentration in the bulk solution (CB CB(o)), it is possible to derive a simplified scaled expression for the relative flux (N/N0) from HPWH s original expressions ... 

When the relative flux is 1, reaction of the basic species with the acid does not contribute to the dissolution of HA since the concentration of B is too low relative to the saturated solubility of HA to impact the dissolution rate (CB < Cha )-As the concentration of the basic species in bulk increases (CB CHa ), the relative flux will approximately double and the reaction of B with HA will begin to dominate the dissolution process. The utility and elegance of Eq. (8) is that one can estimate the increase in dissolution of an acid due to reaction with a base by simply knowing the base concentration in the dissolution media and the... 

Solving Eq. (16) with the boundary conditions of saturation solubility at the solid surface, Cs(0), sink conditions in the bulk solution, and assuming no convection or reaction contributions, yields... 

CS(0) saturated solubility of dissolving species at solid surface M/L3... 

Zentner and coworkers [24,26] utilized this information in their development of a system that releases this drug over a 24 hr period. The use of NaCl to modulate the release of diltiazem presents an interesting problem in that the concentration of the solubility modifier must be maintained within certain limits and below its saturation solubility within the device. To solve this problem, core formulations were developed that contained both free and encapsulated NaCl. The encapsulated NaCl was prepared by placing a microporous coating of cellulose acetate butyrate containing 20 wt% sorbitol onto sieved NaCl crystals. The coated granules released NaCl over 12-14 hr period via an osmotic mechanism into either water or the core tablet formulation. The in vitro release profile for tablets (core I devices) containing 360 mg of diltiazem HC1 and 100 mg of NaCl equally divided between the immediate release and controlled release fractions... 

A special case in dissolution-limited bioavailability occurs when the assumption of sink condition in vivo fails that is, the drug concentration in the intestine is dose to the saturation solubility. Class IV compounds, according to BCS, are most prone to this situation due to the combination of low solubility and low permeability, although the same could also happen for class II compounds, depending primarily on the ratio between dose and solubility. Non-sink conditions in vivo lead to less than proportional increases of bioavailability for increased doses. This is illustrated in Fig. 21.8, where the fraction of drug absorbed has been simulated by use of an compartmental absorption and intestinal transit model [35] for different doses and for different permeabilities of a low-solubility, aprotic compound. 

II Low solubility/High Peff IVIVC should be possible to establish provided that in vitro relevant dissolution test method are used and drug absorption is limited by dissolution rate rather than saturation solubility... 

The second situation when IVIVC is not likely for class II drugs is where the absorption is limited by the saturation solubility in the gastrointestinal tract rather than the dissolution rate, as discussed in more detail above. In this situation, the drug concentration in the gastrointestinal tract will be close to the saturation solubility, and changes of the dissolution rate will not affect the plasma concentrationtime profile and in vivo bioavailability. Standard in vitro dissolution tests are carried out under sink conditions , i.e., at concentrations well below the saturation solubility. Thus, only effects related to dissolution rate can be predicted in vitro. If more physiologically relevant dissolution media are used, which do not necessarily provide sink conditions , the possibility for IVIVC could be improved, as has been indicated by the results of recent studies using simulated intestinal medium [76],... 

For highly permeable, poorly soluble drugs given in lower doses, the dissolution rate rather than the saturation solubility is the limiting factor. An increase in dissolution rate due to in vivo solubilization mediated by food intake could theoretically be obtained, but this situation is not always found in vivo. For example, food does not affect the rate and extent of bioavailability for candesartan cilexitil, a very poorly soluble compound [78], An in vitro dissolution and solubility study of this compound in simulated intestinal media provided a potential explanation it was revealed that the solubility was increased as a function of bile concentration as expected, whereas the dissolution rate was not increased by the higher bile concentrations being representative for the fed state (see Fig. 21.14). Thus, although... 

Fig. 21.14. In vitro dissolution rate versus saturation solubility for candersartan cilexitil in different concentrations of sodium taurocholate lecithin ratio 2.5 1.

A disperse dye suspension responds somewhat differently when a surface-active solubilising agent is added. At low concentrations of this type of additive the saturation solubility of the dye remains relatively little changed, but when the critical micelle concentration of the surfactant is reached a sudden marked increase in dye solubility is observed [57]. When micelles of the surfactant begin to form in the solution, these provide a more amenable environment into which the dye molecules or dimers can transfer. Above the critical micelle concentration the increase in solubility of the dye is directly proportional to the concentration of surfactant present [1,56]. 

Measurements of aqueous solubility and partition coefficient between cellulose acetate and water were compared for thirty disperse dyes and an approximate inverse relationship was postulated [60]. This can only be valid to a limited extent, however, because the partition ratio also depends on the saturation solubility of the dye in cellulose acetate. This property varies from dye to dye and is not directly related to aqueous solubility. The solubilities of four dyes in a range of solvents were compared with their saturation values on cellulose acetate. Solubilities in benzene showed no significant correlation. With the other solvents the degree of correlation increased in the order ethanol < ethyl acetate < 20% aqueous diethylene glycol diacetate (CH3COOCH2CH2OCH2CH2OCOCH3). The last-named compound was suggested as a model with polar groups similar to those in cellulose acetate [86]. 

In order to achieve efficient build-up to heavy depths when dyeing cellulose acetate at 80 °C it is customary, particularly for navy blues, to use a mixture of two or more components of similar hue. If these behave independently, each will give its saturation solubility in the fibre. In practice, certain mixtures of dyes with closely related structures are 20-50% less soluble in cellulose acetate than predicted from the sum of their individual solubilities [87]. Dyes of this kind form mixed crystals in which the components are able to replace one another in the crystal lattice. The melting point depends on composition, varying gradually between those of the components, and the mixed crystals exhibit lower solubility than the sum of solubilities of the component dyes [88]. Dyes of dissimilar molecular shape do not form mixed crystals, the melting point curve of the mixture shows a eutectic point and they behave additively in mixtures with respect to solubility in water and in the fibre. 

There is a roughly inverse relationship for a series of structurally related dyes between the time of half-dyeing and the saturation solubility in an appropriate substrate, as illustrated for several 4-alkylamino derivatives of 1-anilinoanthraquinone on cellulose acetate (Table 3.17). It is interesting that methylamino and 2-hydroxyethylamino substituents confer good solubility in this substrate, but ethylamino groups are even less effective than isobutylamino groups in this respect [114]. 

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