Momose Wataru, Yoshino Hiroyuki, Katakawa Yoshifumi, Yamashita Kazunari, Imai Keiji, Sako Kazuhiro, Kato Eiji, Irisawa Akiyoshi, Yonemochi Etsuo, Terada Katsuhide
Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan ; Faculty of Pharmaceutical Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan ; PAT Committee, Japan Society of Pharmaceutical Machinery and Engineering, Miyoshi Bld. 3F, 2-7-3 Kandata-cho, Chiyoda-ku, Tokyo 101-0046, Japan.
Pharmaceutical Research & Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan.
Results Pharma Sci. 2012 Apr 13;2:29-37. doi: 10.1016/j.rinphs.2012.04.001. eCollection 2012.
Here, we describe a nondestructive approach using terahertz wave to detect crack initiation in a film-coated layer on a drug tablet. During scale-up and scale-down of the film coating process, differences in film density and gaps between the film-coated layer and the uncoated tablet were generated due to differences in film coating process parameters, such as the tablet-filling rate in the coating machine, spray pressure, and gas-liquid ratio etc. Tablets using the PEO/PEG formulation were employed as uncoated tablets. We found that heat and humidity caused tablets to swell, thereby breaking the film-coated layer. Using our novel approach with terahertz wave nondestructively detect film surface density (FSD) and interface density differences (IDDs) between the film-coated layer and an uncoated tablet. We also found that a reduced FSD and IDD between the film-coated layer and uncoated tablet increased the risk of crack initiation in the film-coated layer, thereby enabling us to nondestructively predict initiation of cracks in the film-coated layer. Using this method, crack initiation can be nondestructively assessed in swelling tablets after the film coating process without conducting accelerated stability tests, and film coating process parameters during scale-up and scale-down studies can be appropriately established.
在此，我们描述了一种使用太赫兹波检测药物片剂包衣层中裂纹萌生的无损方法。在包衣工艺放大和缩小过程中，由于包衣工艺参数的差异，如包衣机中的片剂填充率、喷雾压力和气液比等，导致包衣层的膜密度以及包衣层与未包衣片剂之间的间隙存在差异。使用聚氧化乙烯/聚乙二醇配方的片剂作为未包衣片剂。我们发现，热和湿度会使片剂膨胀，从而破坏包衣层。利用我们的太赫兹波新方法可无损检测包衣层的膜表面密度（FSD）以及包衣层与未包衣片剂之间的界面密度差异（IDD）。我们还发现，包衣层与未包衣片剂之间FSD和IDD的降低会增加包衣层中裂纹萌生的风险，从而使我们能够无损预测包衣层中裂纹的萌生。使用这种方法，无需进行加速稳定性试验，就可以在包衣工艺后的膨胀片剂中无损评估裂纹萌生情况，并且可以适当地确定放大和缩小研究过程中的包衣工艺参数。
