Abe Toshihide, Yanagihara Yoshitsugu, Uchino Tomonobu, Oriyama Toyohito, Komatsu Mamoru, Nakajima Katsuyoshi, Suzuki Hiroshi
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo.
Chem Pharm Bull (Tokyo). 2014;62(7):617-26. doi: 10.1248/cpb.c13-00580.
The formulation characteristics of 6 brands of enteric-coated aspirin tablets under unpackaged conditions at 40°C and 60°C for 4 weeks were analyzed. Appearance, salicylic acid content, dissolution rates, and surface properties (by Raman microscopy) were evaluated to determine stability data, taking into account the clinical use of generic drugs. No change in appearance, decomposition, or dissolution rates was observed in unpackaged aspirin tablets stored at 40°C for 4 weeks. However, when stored at 60°C, tablets of 5 of the 6 brands showed whiskers on their surfaces along with an increase in salicylic acid content and a decrease in dissolution rate. Results of Raman mapping on the surface and cross sectional surface of the tablets with whiskers showed a salicylic acid peak associated with storage at 60°C for 4 weeks. However, for tablets from 1 of the 6 brands, no salicylic acid peaks were observed. For this tablet, Raman microscopy revealed 2 layers of film coating, and talc, which greatly affected the stability of the acetylsalicylic acid, was found only in the outer layer film. These results indicated that the protection of compatibility with talc is one of the important factors in enhancement of aspirin tablet stability in this tablet. We concluded that certification of the characteristics associated with stability and formulation is essential for generic drugs, which are not required to undergo stability testing under extreme storage conditions.
分析了6个品牌的肠溶阿司匹林片在40°C和60°C无包装条件下放置4周后的制剂特性。考虑到仿制药的临床应用，对外观、水杨酸含量、溶出率和表面性质（通过拉曼显微镜）进行评估以确定稳定性数据。在40°C下无包装储存4周的阿司匹林片未观察到外观、分解或溶出率的变化。然而，在60°C储存时，6个品牌中的5个品牌的片剂表面出现晶须，同时水杨酸含量增加，溶出率降低。对有晶须的片剂表面和横截面进行拉曼映射的结果显示，存在与在60°C下储存4周相关的水杨酸峰。然而，对于6个品牌中的1个品牌的片剂，未观察到水杨酸峰。对于该片剂，拉曼显微镜显示有两层薄膜包衣，且仅在外层薄膜中发现了对乙酰水杨酸稳定性有很大影响的滑石粉。这些结果表明，在该片剂中，与滑石粉的相容性保护是提高阿司匹林片稳定性的重要因素之一。我们得出结论，对于仿制药而言，对与稳定性和制剂相关的特性进行认证至关重要，因为仿制药无需在极端储存条件下进行稳定性测试。
