Aqueous humour oSulfamerazine Methazolamide

Sulfadiazine Sulfamethazone ° Sulfanilamide Acetazolamide

0 Sulfathiazole




CHCl3 / H2O Partition coefficient

Figure 5.11 (a) Penetration rates of sulfonamides from plasma into rat brain and into canine cerebrospinal fluid. Dog cerebrospinal fluid data from D. P. Rall, J. Pharm Exp. Ther., 125, 185 (1959). (b) Penetration rates of sulfonamides from plasma into aqueous humour for the rabbit (O) and for the rat (•) against partition coefficients (chloroform/water). Data from P. J. Wistrand, Acta Pharmacol. Toxicol., 17, 337 (1960) and A. Sorsby, Br. J. Ophthalmol., 33, 347 (1949).

The toxicity of some agents such as X-ray contrast media and penicillins has also been related to lipophilicity. Rates of entry into the brain of X-ray contrast agents used in cerebral angiography are proportional to P, and P correlates with clinical neurotoxicity. Figure 5.13 shows the positive relationship between toxicity of the penicillins and partition coefficient.

5.10.2 Sorption

Figure 5.14 summarises the physicochemical problems in the use of preservative molecules in formulations. Solubility and partition coefficients of ionised species are determined, as we have seen, by the pH and ionic strength of the system. In this example, partitioning may occur from the aqueous phase to the oily

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