a Reproduced from reference 6.

Steroid solubility

The steroids as a group tend to be poorly soluble in water. Their complex structure makes prediction of solubility somewhat difficult, but one can generally rationalise, post hoc, the solubility values of related steroids. Table 5.6 gives solubility data for 14 steroids. As examples, the substitution of an ethinyl group has conferred increased solubility on the estradiol molecule, as would be expected. Estradiol benzoate with its 3-OH substituent is much less soluble than the parent estradiol because of the loss of the hydroxyl and its substitution with a hydrophobic group. The same relationships are seen in testosterone and testosterone propionate. As both estradiol benzoate and testosterone propionate are oil soluble, they are used as solutions in castor oil and sesame oil for intramuscular and subcutaneous injection (see Chapter 9).

Methyltestosterone might be expected to be less soluble in water than is testosterone, but in fact it is not; this demonstrates again the importance of crystal properties in determining solubility. The methyl compound is more soluble because of the smaller heat of fusion of this derivative, hence the solid state more readily 'disintegrates' in the solvent.

Dexamethasone and betamethasone are isomeric fluorinated derivatives of methyl-prednisolone, but their solubilities are not identical, which might be a crystal property or a solution property. A simpler example of differences in isomeric solubility is that of the o-, m-, and p-dihydroxybenzenes referred to above. A steric argument may be applied to the case of dexamethasone, water molecules being less able to move close to the 17-OH group than in the case of betamethasone.

5.2.2 Hydration and solvation

The way in which solute molecules interact with the water molecules of the solvent is crucial to determining their affinity for the

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