title: Effect of gel formation on the dissolution behavior of clarithromycin tablets.
abstract: Clarithromycin (CAM) is a macrolide antibiotic that is widely used at clinical sites. We found that release of CAM is suppressed when tablets of CAM were exposed to an external solvent containing carboxylate buffers such as citrate. The suppressed release of CAM can be attributed to the formation of gels on the tablet surfaces, which inhibits penetration of the solvent into the tablet and thus disintegration of the tablets. Delayed disintegration of the tablets was also observed for commercial tablets. This suggests that taking CAM and carboxylates at the same time might be avoided. The crystal structure of CAM citrate reveals that molecular chains of CAM are cross-linked by hydrogen bond between citrate groups in the crystal. The crystal structure indicates that cross-linked CAM chains of the three-dimensional mesh structure might also be formed in high concentration CAM solutions in the presence of carboxylates, resulting in gel formation.
authors.affiliation: Department of Pharmaceutical Engineering, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Inukai
authors.affiliation: Department of Pharmaceutical Engineering, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takiyama
authors.affiliation: Department of Pharmaceutical Engineering, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan; Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: Department of Pharmaceutical Engineering, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwao
authors.affiliation: Department of Pharmaceutical Engineering, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: s-itai@u-shizuoka-ken.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Itai
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D017291:Clarithromycin / Q000737:chemistry*; D005782:Gels; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D005782:Gels; D013607:Tablets; D017291:Clarithromycin
keywords: Carboxylate buffer; Clarithromycin; Gelation; Single-crystal X-ray diffraction