Development of manufacturing method for rapidly disintegrating oral tablets using the crystalline transition of amorphous sucrose.
The industrial manufacturing of rapidly disintegrating oral tablets with a sufficient tensile strength was investigated. The manufacturing method of the tablets involved the crystalline transition of amorphous sucrose that was produced in the process of fluidized bed granulation of mannitol using sucrose solution as a binder. The aim of this article was to clarify the usefulness of amorphous sucrose formed during the granulation for the rapidly disintegrating oral tablets manufacturing, and to investigate the effects of crystalline transition of the amorphous sucrose in granules on the characteristics of the resultant tablets prepared by this crystalline transition (CT) method. The X-ray diffraction measurement and thermal analysis showed that amorphous sucrose was effectively formed in granules consisting of 95% mannitol and 5% sucrose when the granulation was performed on the condition of water content of 4%. The tensile strength of tablets comprised of the granules, which were compressed before the crystallization of amorphous sucrose, increased remarkably after storage, because new internal solid bridges were formed in the tablets as a result of the crystallization. We conclude that rapidly disintegrating oral tablets can effectively be manufactured by the CT method using the granules obtained by the fluidized bed granulation method.
Sugimoto
Masaaki
M
Pharmaceutical Development Laboratories, Tanabe Seiyaku Co., Ltd., 16-89 Kashima 3-chome, Yodogawa-ku, Osaka 532-8505, Japan. sugimoto@tanabe.co.jp
Narisawa
Shinji
S
Matsubara
Koji
K
Yoshino
Hiroyuki
H
Nakano
Minoru
M
Handa
Tetsurou
T
D000284:Administration, Oral; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D018360:Crystallography, X-Ray; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D008353:Mannitol / Q000737:chemistry*; D016062:Porosity; D012995:Solubility; D013395:Sucrose / Q000737:chemistry*; D013607:Tablets; D013678:Technology, Pharmaceutical; D013696:Temperature; D013718:Tensile Strength; D013997:Time Factors
D005079:Excipients; D013607:Tablets; D008353:Mannitol; D013395:Sucrose