Biopharmaceutical studies of lipid-containing oral dosage forms: Relationship between drug absorption and gastric emptying of lipid formulations

Gastrointestinal absorption characteristics of drugs in lipid-containing oral dosage forms were studied in rats. A new antiinflammatory agent 1-cyclopropyl-4-phenyl-6-chlor-2 (1H)-quinazolinone (SL-512) was selected as a model of hardly water soluble drugs. Medium chain triglyceride (MCT), medium chain monoglyceride (MCM), and corn oil were used as models of well-digestible lipids, and N-α-methylbenzyllinoleamide (MBLA) for that of hardlydigestible ones. Absorption of orally dosed SL-512 strongly depended on the dose volume of lipid vehicles. Larger volume of lipids (≤100 mcl/rat) delayed absorption of SL-512 due to larger remaining of SL-512 both in the stomach and in the intestine. The gastric retension was also affected by the fluidity of lipids employed. In smaller volume of lipids (5-20 mcl/rat), which has not been examined in previous papers in spite of its compatibility to human clinical dose volume, the amount of intestinal remaining was much less than that of gastric remaining of the preparation. In experiments designed to minimize intestinal remaining of SL-512, serum level of the drug calculated by using gastric emptying rate instead of absorption rate was found to be in good accordance with that of experimental value.