Steroids partition data

Partition Data of Chemotherapeutic and Steroid Agents Determined by Reversed-Phase Thin Layer Chromatography... 

TLC seems to be a suitable technique for determining partition data of antibiotics and steroids. Future determinations should provide further evidence of the relationship between tt and Rm values. 

Somatotropin, the P-adrenergic agonists, and the anaboHc steroids are considered metaboHsm modifiers because these compounds alter protein, Hpid, carbohydrate, mineral metaboHsm, or combinations of these and they partition nutrient use toward greater rates of protein deposition, ie, muscle growth, and lesser rates of Hpid accretion. Historical data leading to understanding of the mechanism (s) of action are found in reviews on anaboHc steroids (1), somatotropin (2—4), and the phenethano1 amines (5—7). 

The solubility data in Table I may be used to test the log P correlations in poly(ethylene-co-vinyl acetate) and polyether-urethanes. The correlations in Equations 19 and 20 are derived by combining this data with the reported (20) water solubilities and octanol-water partition coefficients of the steroids (22-24). 

The micelle/water partition coefficient for many solutes have been shown to correlate to the octanol/ water partition coefficientJ ° Data in Table 8, from Azaz and Donbrow, show that the micellar partition coefficients of the methylphenols increase with the number of methyl groups. Collett and Tobin showed that the micellar partition coefficients of several benzoic acid derivatives are proportional to their octanol-water partition coefficient for poloxamers (Table 9). Tomida et al. also illustrated that most of the 34 monosubstituted benzoic acids with Brij 35 have micellar partition coefficients that are inversely proportional to their aqueous solubilities and proportional to their octanol-water partition coefficients. The data of Tomida, Yotsuyanagi, and Ikeda[ °l for some steroid hormones (Table 10), further illustrate the parallelism between octanol-water and micelle-water partition coefficients. 

A relationship between the lipophilicity of the solubilisate, expressed by the partition coefficient between octanol and water, Poctanoi (see Chapter 5), and its extent of solubilisation has been noted for the soluhilisation of substituted barbituric acids by polyoxyethylene stearates, of substituted benzoic acids by polysorbate 20, and of several steroids by polyoxyethylene nonionic surfactants. An exhaustive survey of data for the solubilisation of some 64 dmgs by bile salt micelles revealed linear relationships between log (partition coefficient between micelles and water) and log Poctanoi ach of seven bile salts... 

The relatively high fractions of Db/Pt for all steroids suggest that permeation through p-HEMA membrane is dominated by the "pore" mechanism. The high Kd values are consistent with the proposed model. According to the model and data obtained in the p-HEMA membrane, partitioning of hydrophobic solutes is governed predominantly by A type domains. Solute within these domains makes a small contribution to permeability. Solute permeation is dominated by the "pore" mechanism. 

Based on partition coefficient data, the hydrophilic solutes examined appear to permeate p-HEMA and p-HEMA with 1 mole % EGDMA via "bulk-like" water regions. Partition coefficients of steroids in p-HEMA are dominated by their high solubility of the steroids in the hydrophobic regions of the hydrogels or A domains, whereas, permeation is dominated by diffusion within "fluctuating pores."... 

Fig. 8. Relation between decane/watcr partition eoeffident (abscissa) and octanol/water partition coefficient (ordinate) for some steroids. Data from Giorgi and Stein [19]. The straight lines have slopes as indicated. Steroids are numbered as follows 41, progesterone 42, corticosterone 43, cortisone 44, cortisol 45, dexamethasone 46, (5,o)-dihydrotestosterone 47, testosterone 48, (l7, )-estradiol 49,...

To test whether the barrier for steroids was the same as the barrier for the smaller solutes, Giorgi also measured the permeabilities and partition coefficients for some smaller molecules. Some of these data are reproduced in Fig. 10 as a log/log plot of permeabihty coefficients against n-octanol partition coefficients. Clearly the data for the small solutes and for the steroids fall on a fairly good straight line, suggesting that the same rate law holds for the permeation of the steroids as for that of the smaller solutes. All seem to encounter a rate-limiting permeability barrier which has... 

Fig. 10. Calculated intramembrane diffusion coefficients across membranes of (A) Nil 8 hamster fibroblasts and (B) the HTC rat hepatoma cell line, as a function of molecular weight of the permeant. Ordinate logarithm of membrane thickness, taken as 50-10 cm, multiplied by the permeability coefficient (in cm/sec) and divided by the octanol/water partition coefficient. Abscissa logarithm of molecular weight. Data taken from Giorgi and Stein [19]. Permeants indicated as follows large circle, mean value for all the steroids of Fig. 8 Ur, urea Thw, thiourea Gly, glycerol Ap, antipyrine. Regression lines through the points have slopes of —3.9 for the Nil 8 cells and —3.7 for the HTC cells.

The steroids corticosterone acetate, 11-dehydrocortisone acetate, corticosterone, 11-dehydrocorticosterone, hydrocortisone, and cortisone have been separated by RP-HPTLC. The chromatographic data (Bm) and partition coefficient (logF) values of the compounds have been correlated with the numerical values of topological indices. The most accurate predictions of the Bm and logF values of the selected steroids were achieved by the use of monoparametric equations employing the topological index... 

Probably more work has been carried out on steroid solubilization than on most other classes of drug. In spite of the mass of data the behaviour of some steroid-surfactant systems, especially those containing two steroids, is by no means understood. The use of oil-water partition coefficients allows us to predict with a reasonable degree of precision the rank order solubility of a given steroid of a series in a surfactant, but not yet to relate surfactant properties to micellar capacity. 

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