INVIVO EVALUATION OF A MULTIPARTICULATE FLOATING CONTROLLED RELEASE DOSAGE FORM

The excretion of riboflavine in urine after oral administration of slow release granules with low apparent density (0.65 g ml-1) is compared with that observed after ingestion of heavy granules (1.3 g ml-1) and the solution of the drug. In each instance, a dose of 40 mg riboflavine-5'-phosphate sodium dihydrate (flavine mononucleotide, FMN) was given to 12 volunteers. The median bioavailability is about 18% higher from the floating granules than from the heavy granules, this difference is weakly significant on the 5% error level. After administration of both types of granules the elimination of riboflavine is significantly reduced, being almost 30% lower than after ingestion of the solution. In general the same is true for other characteristics like the maximum of the excretion rate (dU/dt(max)), the mean total residence time (MRT(total, vivo)), the time to the maximum of the excretion rate (t(max)) and the lag time until significant amounts of riboflavine begin to appear in urine (t0). Apparently, the gastric residence time of the floating granules is only slightly increased. Thus, both types of granules pass the absorption window for riboflavine with a significant fraction of FMN not yet released.