Biopharmaceutics of Drugs Administered in Lipid-Containing Dosage Forms I: GI Absorption of Griseofulvin from an Oil-in-Water Emulsion in the Rat

Abstract

The GI absorption characteristics of micronized griseofulvin from an oil-in-water emulsion dosage form, an oil suspension, and an aqueous suspension were assessed in the rat. Although there was a slight delay in the time of occurrence of the peak plasma concentration of griseofulvin following its oral administration in the emulsion, this dosage form produced a mean peak plasma antibiotic level 1.5 and 2.3 times higher than the oil and aqueous suspensions, respectively. In addition, the emulsion dosage form significantly increased the time over which plasma concentrations of drug were maintained above 1 mcg./ml. All six rats dosed with the emulsion attained this 1-mcg./ml. plasma level or greater (mean duration of 7.5 hr.), while only two out of six rats dosed with the aqueous suspension (duration of 3.7 and 4.0 hr., respectively) and four out of six rats dosed with the oil suspension (mean duration of four rats of 3.9 hr.) ever achieved this plasma concentration. Based on area under the plasma concentration versus time curve measurements, it was established that the bioavailability of micronized griseofulvin can be increased 2.5-fold, as compared to an aqueous suspension, by orally administering this relatively water-insoluble antibiotic in an oil-in-water emulsion dosage form.