title: Suppressed Release of Clarithromycin from Tablets by Crystalline Phase Transition of Metastable Polymorph Form I.
abstract: The pharmaceutical properties of clarithromycin (CAM) tablets containing the metastable form I of crystalline CAM were investigated. Although the dissolution rate of form I was higher than that of stable form II, the release of CAM from form I tablet was delayed. Disintegration test and liquid penetration test showed that the disintegration of the tablet delayed because of the slow penetration of an external solution into form I tablet. Investigation by scanning electron microscopy revealed that the surface of form I tablet was covered with fine needle-shaped crystals following an exposure to the external solution. These crystals were identified as form IV crystals by powder X-ray diffraction. The phenomenon that CAM releases from tablet was inhibited by fine crystals spontaneously formed on the tablet surface could be applied to the design of sustained-release formulation systems with high CAM contents by minimizing the amount of functional excipients.
authors.affiliation: Graduate Division of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Fujiki
authors.affiliation: Graduate Division of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Graduate Division of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwao
authors.affiliation: Graduate Division of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: Graduate Division of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Mizoguchi
authors.affiliation: Faculty of Engineering, Tokyo City University, Setagaya-ku, Tokyo, 158-8557, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Iwamura
authors.affiliation: Graduate Division of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Itai
mesh_terms: D000327:Adsorption; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D017291:Clarithromycin / Q000032:analysis / Q000737:chemistry*; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D044367:Phase Transition; D033362:Powder Diffraction; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D014867:Water / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D014867:Water; D012822:Silicon Dioxide; D002482:Cellulose; C008079:hydroxypropylcellulose; D017291:Clarithromycin; C109691:microcrystalline cellulose
keywords: controlled release; hydration; polymorphism; pseudopolymorphism; sustained release; tablet; transition