Pharmacoscintigraphic evaluation of riboflavin-containing microballoons for a floating controlled drug delivery system in healthy humans

Hollow microspheres (microballoons) floating on artificial gastric juice were developed as a floating controlled drug delivery system in the stomach. The intragastric behavior of Tc-99m labelled microballoons (MB) and nonfloating microspheres (NF) (control) following oral administration in fasted and fed humans was investigated by gamma scintigraphy. Simultaneously, pharmacokinetic examination of riboflavin released from MB and NF was conducted in fasted and fed human subjects. In the fed state. MB were dispersed in the upper portion of the stomach; moreover, MB were retained in the stomach up to 300 min compared with NF, which descended gradually into the lower part of stomach within 90 min. In the fasted state, MB floated for approximately 60 min, after which it was removed rapidly via the cyclic activity referred to as the interdigestive migrating motor complex (IMMC). NF were removed more rapidly, i.e., within 60 min. Pharmacokinetic parameters, e.g., excretion half-life time (t(1/2)) and total urinary excretion, were well correlated with the gastric residence time (GRT) determined by the gamma scintigraphy analysis. The present investigation suggests that MB are very useful for improving drug bioavailability, resulting in a more sustained pharmacological action. (C) 2004 Elsevier B.V. All rights reserved.