Solubility of drugs in the presence of gelatin: effect of drug lipophilicity and degree of ionization

The solubility of seven drugs (nitrofurantoin, chlorothiazide, phenobarbita l, prednisolone, griseofulvin, diazepam and piroxicam) in the absence and p resence of gelatin was measured, at three different pH values (3.7, 5.0 and 7.0) at 37 degreesC. Drugs studied had different physicochemical propertie s (log P, pK(a), aqueous solubility) and their solubility in presence of 0. 1 and 0.5%, (w/v) hydrolyzed land in some cases common) gelatin was estimat ed. Results show that the solubility of all drugs is significantly enhanced , especially in the presence of 0.5%;, gelatin. This gelatin-induced enhanc ement in drug solubility is higher in the pH in which acidic drugs are less ionized, especially for the less lipophilic acidic drugs (nitrofurantoin, chlorothiazide). In all cases, drug solubility in presence of gelatin is co rrelated with their aqueous solubility. Therefore, the established relation ships between aqueous and gelatin solubility can be employed to derive an e stimate of the drug solubility in presence of gelatin once its aqueous solu bility is known. With the exception of piroxicam which is highly ionized an d phenobarbital which is relatively soluble, there seems to be a tendency f or larger gelatin-induced increases in solubility as drug lipophilicity inc reases or aqueous solubility decreases. (C) 2001 Elsevier Science B.V. All rights reserved.