Accumulation ratios

Accumulation ratio Several after first and repeated doses Extent of accumulation... 

Excretion - Following oral administration of an 80 mg dose of C-isotretinoin as a liquid suspension, C-activity in blood declined with a half-life of 90 hours. The metabolites of isotretinoin and any conjugates are ultimately excreted in the feces and urine in relatively equal amounts (total of 65% to 83%). After a single 80 mg oral dose of isotretinoin to 74 healthy adult subjects underfed conditions, the mean elimination half-lives of isotretinoin and 4-oxo-isotretinoin were approximately 21 and 24 hours, respectively. After single and multiple doses, the observed accumulation ratios of isotretinoin ranged from 0.9 to 5.43 in patients with cystic acne. 

In the absence of special transport mechanisms (which is not proven, see further in the text), the vacuolar accumulation ratios (VAR) could be predicted from a derivation of the Hendelson-Hasselbach equation using the calculated log/) values. Indeed, for a diacidic base, the log D is a function of the acidity constants (pka) and the partition coefficient (log P) ... 

All bioanalytical data, derived PK data, and safety data were listed and descriptive statistics calculated. Individual and median data were plotted. The log-transformed PK parameters AUC and Cmax were analyzed for dose proportionality. The PK parameters AUC(0-24) and Cmax were also descriptively analyzed for accumulation ratio. 

Table 5 Observed accumulation ratios of geometric mean parameters for XYZ1234. ...

The accumulation ratio (Rac) was similar in both groups with the between subject variability in patients (43 %) higher than in healthy subjects (16 %). 

A number of physicochemical characteristics are used to evaluate the effectiveness of foam separation processes, such as the degree of extraction, accumulation ratio (enrichment factor), selectivity coefficient, carry-away of the liquid, etc. [22,23,45,46]. 

The surfactant distribution between a foam and a solution is characterised by the accumulation ratio (//). There are a minimum (//min) and a maximum (//max) accumulation ratios [3,22-24,44]... 

Equations connecting the accumulation ratio to parameters of foam structure (dispersity, expansion ratio, radius of curvature of Plateau borders) can be derived from the balance equations of the surfactant and the liquid phase, and the data on foam structure. 

Rubin and Gaden [46] who assumed that cl.f = cz..o and that the liquid volume in the foam, could be neglected compared to the total foam volume, derived a relationship for the minimum accumulation ratio... 

Eqs. (10.1), (10.5) and (10.9) make it possible to calculate the accumulation ratio. These formulae can be applied for various liquid distributions between borders and films. 

If the radius of border curvature R is expressed in terms of the capillary pressure, R = pja, the equation for the accumulation ratio becomes... 

Eqs. (10.11) and (10.12) indicate that when T = const and n = const, the accumulation ratio is determined by foam dispersity, while for r = const and a - const, it is determined by the foam expansion ratio and the capillary pressure. 

When the accumulation of a surfactant mixture is carried out, the selectivity of foam separation is evaluated from the selectivity coefficients which are generally represented by the ratios between the accumulation ratio of the i-th (//,) andy-th (Rfj) components [20,23,24]... 

It should be noted that the selectivity coefficient, like the accumulation ratio, is a relative quantity, depending not only on the substance nature but also on the initial surfactant concentration in the solution [3,21,49,50]. 

It can be seen from Eq. (10.45) that only two of the three characteristics of the adsorption accumulation are independent. For instance, at different accumulation ratios, the same degree of extraction can be achieved by the appropriate variations of the water flooding coefficient. 

Fig. 10.2. n/2R vs. accumulation ratio of sodium butyldiphenylsulphonate in a foam the initial surfactant... 

The accumulation ratio //min increases with the decrease in bubble size only if n = const (Eq. (10.11)). If the expansion ratio changes simultaneously with dispersity (as is often the case under the conditions of gravitational drainage since the decrease in foam bubble size results in a decrease in the rate of drainage and in the formation of a low expansion ratio foam at the outlet of the foam generator), then a decrease in bubble size leads to a decrease in mm rather than to its increase [23,67]. 

A study of foam separation of sodium butyldiphenylsulphonate in a low expansion ratio foam has shown [46] that the accumulation ratio increases linearly with the increase in the n/2R value, which is in conformity with Eq. (10.8) (Fig. 10.2). An expansion ratio of more than 100 is rarely achieved in standard separation columns and, therefore, under these conditions the accumulation ratio is of the order of several tens or, occasionally, several hundreds. A large number of papers have been dedicated to the study of the possibility to... 

The influence of the external dephlegmation on the degree of accumulation is illustrated in Fig. 10.3 [75], With the increase in the part of the foam product taken for dephlegmation, the accumulation ratio increases from about 2 (without dephlegmation) to 4-10 depending on the rate of foaming and the initial surfactant concentration. But even at complete reflux of the whole foam product the accumulation ratio remains not very high. 

Fig. 10.3. Dependence of the accumulation ratio of sodium butyldiphenylsulphonate in an external...

Larger values of the accumulation ratio can be reached in dry foams [24,25,47,73,74,76-78]. Kruglyakov and Kuznetsova [47,71] have studied the effect of capillary pressure, foam expansion ratio and dispersity on / mjn. The foam was prepared from NaDoBS and NP20 solutions. The accumulation ratio //m,n increased directly proportional to the expansion ratio (at a = const) and inversely proportional to the parameter a (at n = const) (Fig. 10.4). The maximum degree of accumulation in a NaDoBS solution (0.3 g dm 3 + 0.4 mol dm 3 NaCl) which could be achieved was = 1050 at Ap = 102 kPa. Further increase in... 

Fig. 10.4. Accumulation ratio of a surfactant in a foam vs. foam expansion ratio (a) and dispersity (b) of...

Fig. 10.6. Dependence of the BSA accumulation ratio on its initial concentration in the foaming system at...

Fig. 10.7. Accumulation ratio of saponin (S) (curve 1) and of valeric acid (VA) (curve 2) vs. the...

The process of extraction of a-chymotrypsin from its solutions with adding more effective foaming agents has been also studied [79]. A large accumulation ratio (90) was reached in a system, containing 2-10 5 mol dm"3 of the protein, 10 4 mol dm 3 NaDoS and 0.4... 

The origin of the extremes in the accumulation ratio (//) versus surfactant concentration curves is different for the individual compounds (in particular for proteins [74]) and for mixtures of two surface active components [78], For individual substances a maximum is reached at saturation of the adsorption layer and, respectively, CF after which further increase in concentration Cl leads to decrease in Ef. 

In the study of the accumulation of gelatine and its mixtures with NaDoS it has been established [80] that the maximum degree of accumulation is reached at gelatine/NaDoS ratio of 1.74. This corresponds to formation of gelatine-surfactant complexes [81,82]. The formation of complexes raises considerably foam stability [80]. Under static conditions and using a porous plate cell, the accumulation ratio reaches 100-150 at the isoelectric point of gelatine (pH = 4.8). In the absence of NaDoS, however, and under the optimum conditions (concentration 0.01-0.02% and pH = 4.8), = 10-24. Under dynamic conditions (in a moving... 

The influence of internal foam collapse on the parameters of foam accumulation has been experimentally studied by Khaskova and Kruglyakov [25,51,67], They evaluated the changes in the accumulation ratio and extraction coefficient of both NaDoBS and NaOL foams, that exhibit different kinetics of destruction [51,67]. Fig. 10.8 shows the kinetic dependence of the accumulation ratio and its constituents for NaDoBS foam (see Eq. (10.15)). 

Fig. 10.8. Time dependence of accumulation ratio and its constituents for a NaDoBS foam curve 1 -...

Similar results were obtained for a foam prepared from a NaOL solution. In this case, the effect of foam collapse on the accumulation ratio was even more pronounced. The... 

A negative influence of the foam collapse on accumulation ratio and extraction coefficient has also been found [51,67] when separation of foams of various stability was carried out under gravitational drainage. Over a wide range of concentrations of the surfactant being extracted these coefficients decreased as a result of internal foam collapse. 

A positive influence of the internal collapse (internal dephlegmation) on the accumulation ratio (i.e. its increase) was observed only in the cases where a very small cl.o value lies in the range cm < c 0 < cr (cr, corresponds to the saturated adsorption layer). The reason is that desorption from film surfaces during foam collapse increases surfactant concentration in the foam liquid phase, and, as a consequence, the degree of adsorption increases to values that ensure the formation of a small volume of a stable foam. Therefore, it becomes possible to separate the foam from the original solution with Rf>. ... 

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