title: Application of water-insoluble polymers to orally disintegrating tablets treated by high-pressure carbon dioxide gas.
abstract: The phase transition of pharmaceutical excipients that can be induced by humidifying or heating is well-known to increase the hardness of orally disintegrating tablets (ODTs). However, these conditions are not applicable to drug substances that are chemically unstable against such stressors. Here, we describe a system which enhances the hardness of tablets containing water-insoluble polymers by using high-pressure carbon dioxide (CO2). On screening of 26 polymeric excipients, aminoalkyl methacrylate copolymer E (AMCE) markedly increased tablet hardness (+155N) when maintained in a high-pressure CO2 environment. ODTs containing 10% AMCE were prepared and treatment with 4.0MPa CO2 gas at 25°C for 10min increased the hardness to +30N, whose level corresponded to heating at 70°C for 720min. In addition, we confirmed the effects of CO2 pressure, temperature, treatment time, and AMCE content on the physical properties of ODTs. Optimal pressure of CO2 gas was considered to be approximately 3.5MPa for an AMCE formula, as excessive pressure delayed the disintegration of ODTs. Combination of high-pressure CO2 gas and AMCE is a prospective approach for increasing the tablet hardness for ODTs, and can be conducted without additional heat or moisture stress using a simple apparatus.
authors.affiliation: Pharmaceutical Research and Technology Labs., Astellas Pharma Co., Ltd., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan; Department of Pharmaceutical Engineering, Graduate Division of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Pharmaceutical Research and Technology Labs., Astellas Pharma Co., Ltd., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Pharmaceutical Research and Technology Labs., Astellas Pharma Co., Ltd., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Department of Pharmaceutical Engineering, Graduate Division 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 Division of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: Department of Pharmaceutical Engineering, Graduate Division 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: D000284:Administration, Oral; D002245:Carbon Dioxide / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D013607:Tablets; D014867:Water / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011108:Polymers; D013607:Tablets; D014867:Water; D002245:Carbon Dioxide
keywords: Aminoalkyl methacrylate copolymer e; Carbon dioxide; Orally disintegrating tablet