「患者にやさしい製剤」の設計と評価

－ポリエチレンオキサイド-カラギーナン混合物の院内製剤基剤への応用－

抄録

Stomatitis, an inflammation of the mucous lining of the mouth, is a harmful adverse effect of high or multiple dosing of cytotoxic agents such as 5-fluorouracil. To prevent stomatitis induced by such cancer chemotherapy, oral dosage forms including radical scavenging agents such as allopurinol (APN) or rebamipide have been prepared. In the present study, the pharmaceutical utility of a gel or mouthwash consisting of polyethylene (oxide) (PEO) and carrageenan (κ- CG or ι-CG) was investigated as an oral dosage preparation with the potential for greater ease of handling and swallowing. Examination of the gelation behavior of preparations with a variety of PEO and/or CG concentrations and handling of the gelled material indicated that the optimum gel compositions (PEO : ι-CG % ratio) were 0.5 : 2.0, 1.0 : 2.0 and 2.0 : 2.0. From the results of sensory testing, it was determined that ι-CG was a more suitable gel material because it has no taste or odor, unlike κ-CG which has its own special taste and odor. The release behavior of APN from APN gels was investigated by the paddle-bead method, mimicking the chewing action. The APN gel was effectively sheared by the beads and the release of APN completed within 480 s. The results of sensory testing confirmed that an APN gel containing 2.0 % ι-CG and 1.0 % PEO was the best type as it produced a jelly-like preparation. In the case of mouthwashes, the adhesiveness of the drug was found to increase as the concentration of PEO increased, and the adhesion of a mouthwash containing PEO was greater than one containing sodium carboxymethylcellulose (CMC-Na). When APN was dissolved in a mixture of PEO-ι-CG and sprayed onto the oral mucosa, the preventive effect against stomatitis was greater than that of a mouthwash containing APN and CMC-Na. The results obtained in this study indicate that a mixture of PEO and ι-CG may be a useful new dosage form for improving patient adherence to medication.