In vitro and in vivo evaluation of riboflavin-containing microballoons for a floating controlled drug delivery system in healthy humans.

Microballoons (MB) possessing a spherical cavity enclosed within a hard polymer shell have been developed as a dosage form characterized by excellent buoyancy in the stomach. MB were prepared by the emulsion solvent diffusion method using enteric acrylic polymers dissolved in a mixture of dichloromethane and ethanol. Riboflavin-containing MB were administered orally to each of three healthy volunteers. The pharmacokinetics of riboflavin was investigated by analysis of the urinary excretion. Prolongation of the urinary excretion of riboflavin could be obtained by ingestion of water as well as "fed" conditions. This phenomenon was attributable to the buoyancy properties of MB in the stomach and an increase in the gastric residence time (GRT). The excretion half-life time (t(1/2)) following administration of MB (particle size: 500-1000 microm) exhibiting high buoyancy was longer than that of MB (particle size: <500 microm) displaying low buoyancy. Therefore, the intragastric floating properties of MB are potentially beneficial as far as a sustained pharmacological action is concerned. MB prepared by mixing it with hydroxypropylmethylcellulose (HPMC) in different ratio, results in improved riboflavin-release properties. These MB were evaluated in vivo by analysis of the urinary excretion of riboflavin. As a result, strong correlations were observed between the buoyancy and excretion half-life (t(1/2)) and between the riboflavin release from the MB and total urinary excretion.