Chem. Pharm. Bull. 54(4) 514—518 (2006)

method of administering therapeutic agent for their systematic effects such as patient acceptance, convenience in administration, and cost-effective manufacturing process. Thus, a wide variety of approaches of drug delivery system (DDS) have been investigated for oral application. However, the development process is precluded by several physiological difficulties, such as an inability to restrain and localize the DDS within desired regions of gastrointestinal tract and highly variable nature of gastric emptying process. For example, the relatively brief gastric emptying time (GET) can result in incomplete drug release from the DDS devices leading to diminished efficacy of the administered dose. Intragastric floating drug delivery system (FDDS) is noted as one of the orally applicable DDS for prolongation of the GET. The bulk density of FDDS is lower than that of gastric fluids and thus it remains buoyant on stomach contents for a long time in the drug releasing process. Hence, it is useful for obtaining the sufficient bioavailability and the effective “plasma” level, especially for drug having limited absorption sites in the upper small intestine, such as furosemide, ketoprofen. In addition, FDDS is one of the optimal systems for stomach mucosa targeting of antitumor agent for the treatment of stomach cancer and antibiotics for the eradication of Helicobacter pylori. However, with most of FDDS devices developed previously, it is difficult for all patients to obtain the expected therapeutic effects of drug administered, since the drug is released with a pattern preprogrammed in the manufacturing process despite individual differences in stomach such as pH value and the transit time in gastrointestinal tract. Thus, from a viewpoint of the real optimization of drug therapy, the drug release properties of FDDS should be adjusted to individual stomach conditions. Over the years, in a series on preparation of double-compressed (DC) tablets for use in a DDS with plasma techniques, we have reported that novel sustainedand delayedrelease systems can be prepared by plasma-irradiation on the outer layer of DC tablet, as well as matrix-type composite powder for sustained-drug release system can be prepared by mechanically-amplified plasma processing. During the course of such studies on plasma-assisted DDS preparation, we have found that the carbon dioxide was trapped in the tablet when argon plasma was irradiated onto the DC tablet composed of plasma-crosslinkable polymers possessing carboxyl group as an outer layer. Since such tablets turned to floating system on the water, it was considered that this could be applicable to FDDS. In fact, we have obtained the intragastric FDDS by plasma-irradiation on DC tablet using a mixture of methyl vinyl ether–maleic acid copolymer (VEMAC) and hydroxypropylmethylcellulose phthalate (HPMCP) with plasma-crosslinkable properties as outer layer. The tablet thus plasma-irradiated had a floating ability in simulated gastric fluid and the drug release from tablet could be controlled at a desired rate by selecting plasma operational consitions. Based on the findings obtained from plasma-assisted FDDS preparation with VEMAC, we examined the possibility of preparation of DC tablet of 5-fluorouracil (5-FU) with outer layer using polymers approved as pharmaceutical aids, water-soluble poly(N-vinylpyrrolidone) (PVP) and waterinsoluble ethylacrylate–methylmethacrylate–trimethylaminoethylmethacrylate chloride copolymer (E-RL), commercially known as Povidone and Eudragit RL, respectively. Figure 1 shows the structures of PVP and E-RL. They are classified as plasma-crosslinkable polymers because of presence of typical plasma-crosslinkable monosubstituted vinyl monomers in the component. And, NaHCO3 powder was added to the outer layer with expectation that evolved gases generated by plasma-induced thermal decomposition of NaHCO3 would be effectively trapped in the bulk phase of outer layer, leading to decrease in density of the tablet. We report here the detailed account of the preparation of such a FDDS by plasma techniques. 514 Vol. 54, No. 4 Chem. Pharm. Bull. 54(4) 514—518 (2006)