A NEW MULTIPLE-UNIT ORAL FLOATING DOSAGE SYSTEM .2. INVIVO EVALUATION OF FLOATING AND SUSTAINED-RELEASE CHARACTERISTICS WITH PARA-AMINOBENZOIC ACID AND ISOSORBIDE DINITRATE AS MODEL-DRUGS

In a previous study, we developed a multiple-unit type of oral floating dosage system, which is a new type of floating pill composed of both an effervescent layer and a swellable membrane layer coated on sustained-release pills. The system was shown to have excellent floating ability and sustained-release characteristics in vitro, irrespective of the pH and viscosity of the medium. In the present study, the floating ability and the sustained-release characteristics of the system in the gastrointestinal tract have been evaluated in vivo. In beagle dogs and humans in the fed state, most of the new type of pills containing barium sulfate were floating in the stomach at 10 min, and they kept floating for at least 3 h after administration (observed by periodic X-ray photographs), while some control pills without the effervescent layers were already transited into the small intestine by 3 h. Moreover, in order to evaluate the sustained-release characteristics of the drug from the new type of floating pills, p-aminobenzoic acid (PABA), with a limited absorption site, and isosorbide dinitrate (ISDN), with wide absorption sites in the gastrointestinal tract, were employed as model drugs. Floating pills of the new type, with the same sustained-release rate as that of non-floating pills (control pills) were prepared. In beagle dogs in the fed state, the new type of floating pills containing PABA showed higher plasma PABA levels at 5 and 6 h after dosing and 1.61 times greater AUC than the control pills. This result suggests that the new type of floating pills attain longer sustained-release and improve the bioavailability of drugs with an absorption window in the upper intestinal tract. However, plasma ISDN profiles of the new type of floating pills in beagle dogs in the fed state were almost the same as those of control pills. Therefore, it is suggested that, for drugs with wide absorption sites in the intestine such as ISDN, the difference of the gastric emptying time between the floating pills and the control pills is not likely to be reflected in the plasma drug profiles.