Towa Pharmaceutical Co., Ltd., 26-7 Ichiban-Cho, Kadoma, Osaka 571-0033, Japan.
Int J Pharm. 2009 Dec 1;382(1-2):80-7. doi: 10.1016/j.ijpharm.2009.08.010. Epub 2009 Aug 15.
The aim of this study was to design a new orally disintegrating tablet (ODT) that has high tablet hardness and a fast oral disintegration rate using a new preparation method. To obtain rapid disintegration granules (RDGs), a saccharide, such as trehalose, mannitol, or lactose, was spray-coated with a suspension of corn starch using a fluidized-bed granulator (suspension method). As an additional disintegrant, crospovidone, light anhydrous silicic acid, or hydroxypropyl starch was also included in the suspension. The RDGs obtained possessed extremely large surface areas, narrow particle size distribution, and numerous micro-pores. When tabletting these RDGs, it was found that the RDGs increased tablet hardness by decreasing plastic deformation and increasing the contact frequency between granules. In all tablets, a linear relationship was observed between tablet hardness and oral disintegration time. From each linear correlation line, a slope (D/H value) and an intercept (D/H(0) value) were calculated. Tablets with small D/H and D/H(0) values could disintegrate immediately in the oral cavity regardless of the tablet hardness and were considered to be appropriate for ODTs. Therefore, these values were used as key parameters to select better ODTs. Of all the RDGs prepared in this study, mannitol spray-coated with a suspension of corn starch and crospovidone (2.5:1 w/w ratio) showed most appropriate properties for ODTs; fast in vivo oral disintegration time, and high tablet hardness. In conclusion, this simple method to prepare superior formulations for new ODTs was established by spray-coating mannitol with a suspension of appropriate disintegrants.
本研究旨在设计一种新的口腔崩解片（ODT），采用新的制备方法，使片剂具有较高的硬度和快速的口腔崩解速率。为了获得快速崩解颗粒（RDG），可以使用流化床造粒机（悬浮法）将甘露糖醇、甘露醇或乳糖等糖类用玉米淀粉混悬液喷雾包衣。作为额外的崩解剂，还可以将交联聚维酮、轻质无水硅酸或羟丙基淀粉加入到混悬液中。所得 RDG 具有非常大的表面积、狭窄的粒径分布和众多的微孔。当将这些 RDG 压片时，发现 RDG 通过减少塑性变形和增加颗粒之间的接触频率来增加片剂的硬度。在所有片剂中，片剂硬度与口腔崩解时间之间存在线性关系。从每条线性相关线中，计算斜率（D/H 值）和截距（D/H(0) 值）。硬度和口腔崩解时间无关，无论片剂硬度如何，片剂硬度较小且 D/H(0) 值较小的片剂都可以立即在口腔中崩解，被认为适合作为 ODT。因此，这些值被用作选择更好的 ODT 的关键参数。在所研究的所有 RDG 中，用玉米淀粉和交联聚维酮（2.5:1 w/w 比例）混悬液喷雾包衣的甘露糖醇显示出最适合作为 ODT 的性质；具有较快的体内口腔崩解时间和较高的片剂硬度。总之，通过用合适的崩解剂混悬液喷雾包衣甘露糖醇，建立了一种简单的方法来制备新的 ODT 的优质配方。
