R

Deoxycorticosterone R = — COCH2OH

Deoxycorticosterone R = — COCH2OH

is particularly pronounced with some non-ionic surfactants, where it is a consequence of an increase in the micellar size with increase in temperature. Table 6.12 shows an increased solubilisation of two drugs by aqueous micellar solutions of bile salts as temperature is increased over the range 27 to 45°C.

A complicating factor when considering the effect of temperature on the amount solu-bilised is the change in the aqueous solubility of the solubilisate with temperature increase. In some cases, although the amount of drug that can be taken up by a surfactant solution increases with temperature increase, this may simply reflect an increase in the amount of drug dissolved in the aqueous phase rather than an increased solubilisation by the micelles. This point is illustrated by a study of the solubilisation of benzoic acid by a series of polyoxyethylated nonionic surfactants, details of which are given in Table 6.13. Although the extent of solubilisation of benzoic acid increases with temperature, the micelle/water distribution coefficient, Pm, shows a minimum at about 27°C. The decrease in Pm (and therefore the amount of drug solubilised in the micelles) with temperature increase up to this temperature is possibly due to the increase in aqueous solubility of benzoic acid; the subsequent increase of Pm at higher temperatures is due to a rapid increase of micellar size as the cloud point is approached and a consequent ability of the micelles to incorporate more solubilisate.

6.6.4 Pharmaceutical applications of solubilisation

A wide range of insoluble drugs has been formulated using the principle of solubilisation. Only a few representative examples will be discussed in this section.

Phenolic compounds such as cresol, chloro-cresol, chloroxylenol and thymol are frequently solubilised with soap to form clear solutions which are widely used for disinfection. Solution of Chloroxylenol BP, for example, contains 5% w/v chloroxylenol with terpineol in an alcoholic soap solution.

Table 6.12 The effect of temperature on the maximum additive concentrations (MAC) of griseofulvin and hexestrol in bile saltsa

Solubilisate Bile salt 103MAC (moles solubilisate/mole surfactant)

Table 6.12 The effect of temperature on the maximum additive concentrations (MAC) of griseofulvin and hexestrol in bile saltsa

Solubilisate Bile salt 103MAC (moles solubilisate/mole surfactant)

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