Application of water-insoluble polymers to orally disintegrating tablets treated by high-pressure carbon dioxide gas

作者：Ito Yoshitaka; Maeda Atsushi; Kondo Hiromu; Iwao Yasunori; Noguchi Shuji; Itai Shigeru^*

来源：International Journal of Pharmaceutics, 2016, 511(1): 10-22.

DOI：10.1016/j.ijpharm.2016.06.132

• Orally disintegrating tablet
• Carbon dioxide
• Aminoalkyl methacrylate copolymere

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 (+155 N) when maintained in a high-pressure CO2 environment. ODTs containing 10% AMCE were prepared and treatment with 4.0 MPa CO2 gas at 25 degrees C for 10 min increased the hardness to +30 N, whose level corresponded to heating at 70 degrees C for 720 min. 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 3.5 MPa 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.

• 出版日期2016-9-10