Absorbed fractions

Typical Fractionator-Absorber/Stripper Design Number of Troys... 

Calculate fraction absorbed for each component, assuming a fixed overall tray efficiency for an... 

Read Eaj values for fraction absorbed from Figure 8-58 using the A values of Step 9 and the fixed or assumed theoretical trays. 

As a rough approximation, assume the fraction absorbed of a given component is inversely proportional to its Kralue (Equation 8-202). For example ... 

Absorption Efficiency, or fraction absorbed Overall tray efficiency, fraction Stripping efficiency, or fraction stripped Fraction of v + li absorbed by the liquid Fraction of loi stripped out of the liquid Mols individual components stripped per hour Total heat of absorption of absorbed components, thousand Btu/day... 

The metabolic and pharmacokinetic profile of sucralose (this is a novel intense sweetener with a potency about 600 times that of sucrose) in human volunteers was studied by Roberts and coworkers [82]. Part of this study was realized using PLC in the following chromatographic system in which the stationary phase was silica gel and the mobile phase was ethyl acetate-methanol-water-concentrated ammonia (60 20 10 2, v/v). Separated substances were scraped off separately, suspended in methanol, and analyzed by filtration, scintillation counting, or enzymatic assay. It was shown that the characteristics of sucralose include poor absorption, rapid elimination, limited conjugative metabolism of the fraction absorbed, and lack of bio-accumulative potential. 

Danelian, E., Karlen, A., Karlsson, R., Winiwarter, S., Hansson, A., Lofas, S., Lennernas, H., Hamalainen, D. SPR biosensor studies of the direct interaction between 27 drugs and a liposome surface correlations with fraction absorbed in humans./. Med. Chem. 2000, 43, 2083-2086. 

For the majority of drugs, the preferred administration route is by oral ingestion which requires good intestinal absorption of drug molecules. Intestinal absorption is usually expressed as fraction absorbed (FA), expressing the percentage of initial dose appearing in a portal vein [15]. 

The amount of a component absorbed or stripped in a column is dependent on the column design (the number of stages), the component solubility, and the gas and liquid rates. The fraction absorbed can be estimated using the absorption factor method, attributed to Kremser (1930) (see Volume 2, Chapter 12). If the concentration of solute in the solvent feed to the column is zero, or can be neglected, then for the solute component the fraction absorbed =... 

If the areas under the curves are denoted by A, then (based on equal dose) All/Al is the fraction absorbed by oral route. Alll/All is the fraction efficiency of the solid dosage form. The reason for this latter is, of course, that the solid dosage form has to dissolve before the drug contained in it is available for absorption. It is the latter ratio that is important to the investigating pharmaceuticist, and therefore the outcome of the parenteral form is actually not a consideration from a formulation point of view. It is critical overall and if it is low, it may, at the point of parenteral data acquisition, be advisable to stop the program and evaluate the possibility of derivatives that would give better availability. 

Bioavailability depends not only on having the drug in solution, but also on the drug s permeability. A jejunal permeability of at least 2-4 x 10 4cm/s, measured in human subjects by intubation, is considered high [97]. For many drugs and other substances, this permeability corresponds to a fraction absorbed of 90% or better. Amidon et al. [97] thus proposed a Biopharmaceutics Classification System (BCS) for drugs based on the above definitions of these two parameters. Table 3 defines the BCS and includes some drugs representative of each class. 

High permeability (fraction absorbed > 90%) Low permeability (fraction absorbed < 90%)... 

Dressman, J. B. Amidon, G. L. Fleisher, D., Absorption potential Estimating the fraction absorbed for orally administered compounds, J. Pharm. Sci. 74, 588-589 (1985). 

Many academic and industrial laboratories have shown that the drug permeability measured in Caco-2 cell monolayers can be used to predict the oral absorption of drugs in humans. Various datasets have therefore been used to establish correlations between Caco-2 permeability and the fraction absorbed orally in humans [85, 86, 96]. Taken together, these studies show good predictability, though with a relatively wide variation in the appearance of correlation profiles between different laboratories [86]. These studies emphasize the need to establish correlations and standardization procedures in each laboratory. 

Another limitation of the Caco-2 monolayers is their colonic origin and tight paracellular pathway, which tend to lead to underestimations in permeability to paracellularly transported compounds [97]. This is likely to be correct for small compounds (MW < 150) - i.e., compounds smaller than normal drugs - but it remains to be seen to what extent the Caco-2 model gives false-negative predictions of the fraction absorbed for polar drugs of normal size in humans where para-... 

Compounds absorbed by active uptake mechanisms (e.g., glucose and Gly-Pro) and compounds known to be substrates for efflux transport (e.g., digoxin, verapamil) were also included in the list. The applied concentration (10-500 pM) only had minor effects on the permeability values. Thus, the choice of concentration was not critical for this set of compounds with respect to the relationship between permeability and fraction absorbed in humans. Changing the pH on the apical donor side had significant effects on the Papp values of several compounds, the effects being in agreement with the acid-base properties of the compounds. The... 

Fig. 5.4. Relationship between the oral fraction absorbed in humans and apparent permeability coefficients obtained in Caco-2 cell monolayers. Papp bands for predicted fraction absorbed of <20% (low), 20-80% (moderate) and >80% (high) are indicated.

Cmin.ss is the minimum plasma concentration at steady state fa is the fraction absorbed in man ... 

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