title: Structural changes of polymer-coated microgranules and excipients on tableting investigated by microtomography using synchrotron X-ray radiation.
abstract: Multiple-unit tablets consisting of polymer-coated microgranules and excipients have a number of advantageous pharmaceutical properties. Polymer-coated microgranules are known to often lose their functionality because of damage to the polymer coating caused by tableting, and the mechanism of polymer coating damage as well as the structural changes of excipients upon tableting had been investigated but without in-situ visualization and quantitative analysis. To elucidate the mechanism of coating damage, the internal structures of multiple-unit tablets were investigated by X-ray computed microtomography using synchrotron X-rays. Cross sectional images of the tablets with sub-micron spatial resolution clearly revealed that void spaces remained around the compressed excipient particles in the tablets containing an excipient composed of cellulose and lactose (Cellactose(®) 80), whereas much smaller void spaces remained in the tablets containing an excipient made of sorbitol (Parteck(®) SI 150). The relationships between the void spaces and the physical properties of the tablets such as hardness and disintegration were investigated. Damage to the polymer coating in tablets was found mainly where polymer-coated microgranules were in direct contact with each other in both types of tablets, which could be attributed to the difference in hardness of excipient particles and the core of the polymer-coated microgranules.
authors: Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Ryusuke
authors: R
authors: Kajihara
authors: Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Shuji
authors: S
authors: Noguchi
authors: Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Yasunori
authors: Y
authors: Iwao
authors: Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-gun, Hyogo 679-5198, Japan.
authors: Yoshio
authors: Y
authors: Suzuki
authors: Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-gun, Hyogo 679-5198, Japan.
authors: Yasuko
authors: Y
authors: Terada
authors: Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-gun, Hyogo 679-5198, Japan.
authors: Kentaro
authors: K
authors: Uesugi
authors: Department of Pharmaceutical Engineering, 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: Shigeru
authors: S
authors: Itai
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D006244:Hardness; D007785:Lactose / Q000737:chemistry*; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013012:Sorbitol / Q000737:chemistry*; D017356:Synchrotrons; D013607:Tablets; D055114:X-Ray Microtomography; D014965:X-Rays
chemical_list: D005079:Excipients; D013607:Tablets; D011092:Polyethylene Glycols; D013012:Sorbitol; D002482:Cellulose; C008079:hydroxypropylcellulose; D007785:Lactose
keywords: Coating damage; Computed microtomography; Multiple-unit tablets; Polymer-coated microgranules; Synchrotron X-ray radiation; Tableting