Comparative bioavailability of anhydrous griseofulvin and its chloroform solvate in man

Using a crossover experimental design, the absorption profile of griseofulvin was assessed in human volunteers after oral administration of a 500 mg dose of the antifungal antibiotic as capsules of the anhydrous (nonsolvated)-and monochloroform solvate forms of the drug. The maximum body level of drug and the rate and extent of griseofulvin absorption (or bioavailability) were significantly increased after administration of the chloroform solvate as compared to that observed after administration of the nonsolvated form of the drug. The enhanced absorption of griseofulvin chloroformate correlated well with its enhanced solubility and dissolution rate at 37 degrees C in simulated intestinal fluid (20 mM sodium deoxycholate, pH 7.5). This is the first demonstration of a drug-organic solvate displaying improved gastrointestinal absorption characteristics over the anhydrous form of a drug.