Steroids partition coefficients

Flynn GL. Structural approach to partitioning estimation of steroid partition coefficients based upon molecular constitution. J Pharm Sci 1971 60(3) 345-353. 

Fig. 12 Predicted versus experimental values for corneal steroid permeability as a function of partition coefficient. 

Figure 20 Correlation of appearance kinetics of steroid permeants across Caco-2 cell monolayers in the Trans well system with log partition coefficients (n-octanol/water) and stirring dependency. 

Schoenwald, R. D., and Ward, R. L. Relationship between steroid permeability across excised rabbit cornea and octanol-water partition coefficients. J. Pharm. Sci. 67(6) 786-788, 1978. 

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 various approaches to estimating diffusion coefficients and solubilities of drugs in polymers have been reviewed. The polymers typically used for drug delivery have diffusion coefficients that are characteristic of the polymer and relatively constant for drugs of a similar molecular size. Drug solubilities in a polymer can be estimated from the solubility parameters and melting points (steroids), from the melting point alone, or from the correlation of partition coefficients. 

Palytoxin is a white, amorphous, hydroscopic solid that has not yet been crystallized. It is insoluble in nonpolar solvents such as chlorophorm, ether, and acetone sparingly soluble in methanol and ethanol and soluble in pyridine, dimethyl sulfoxide, and water. The partition coefficient for the distribution of palytoxin between 1-butanol and water is 0.21 at 25°C based on comparison of the absorbance at 263 nm for the two layers. In aqueous solutions, palytoxin foams on agitation, like a steroidal saponin, probably because of its amphipathic nature. The toxin shows no definite melting point and is resistant to heat but chars at 300°C. It is an optically active compound, having a specific rotation of -i-26° 2° in water. The optical rotatory dispersion curve of palytoxin exhibits a positive Cotton effect with [a]25o being -i-700° and [a]2,j being +600° (Moore and Scheuer 1971 Tan and Lau 2000). 

Table 7. Chemical structure, molecular formula, molecular mass, relative binding affinity (RBA) to the androgen receptor (AR), n-octanol/water partition coefficient (log Kqw)> and bioconcentration factors on a wet weight basis (BCF ) and on a lipid basis (BCFl) of Steroidal Androgens and Nonsteroidal Chemicals with Antiandrogenic Activity... 

Table 10 Micellar partition coefficients of some steroids in Brij 35...

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 assumption made in the model is that A domains are of the same nature in both p-HEMA and crosslinked p-HEMA, If this is strictly true, the partition coefficients which are dominated by A type domains in p-HEMA should be related to partition coefficients in p-HEMA with 5.25 mole % EGDMA according to the volume fraction of A type domains present in p-HEMA. (This volume fraction is 0.772 since "bulk-like" water is 22.8% in p-HEMA.) These values are given in Table V as the ratio Kd(I)/Kd(II), Kd(I) and KdCII) are partition coefficients of steroids in p-HEMA and p-HEMA with 5.25 mole % EGDMA respectively. The estradiol value of... 

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."... 

A plot of some partition coefficients for steroids of different structure, where the decane partition coefficients are plotted against those for octanol, is given in Fig. 8. Decane discriminates far more effectively between these steroids than does n-octanol, a 10-fold range of K values in octanol being transformed into a 1000-fold range in decane. 

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.

Apart from the microemulsion structure and composition, the drug release rate from a microemulsion is expected to depend on the oil/water partitioning of the drug. In the study by Trotta et al. [16] on the release of steroid hormones of different lipophilicities from O/W microemulsions, a correlation was found between the partition coefficients and the release rates of the hormones. 

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