Pandey Preetanshu, Bindra Dilbir S, Gour Shruti, Trinh Jade, Buckley David, Badawy Sherif
Drug Product Science and Technology, Bristol-Myers Squibb1 Squibb Drive, New Brunswick, New Jersey 08901.
Drug Product Science and Technology, Bristol-Myers Squibb1 Squibb Drive, New Brunswick, New Jersey 08901.
J Pharm Sci. 2014 Nov;103(11):3666-3674. doi: 10.1002/jps.24169. Epub 2014 Sep 15.
The objective of this study was to establish the effects of the level of minor formulation components (sodium lauryl sulfate: SLS, and magnesium stearate: MgSt) and manufacturing process on final blend compaction properties and the performance of the tablets during film coating. A 2 × 2 × 3 factorial study was conducted at two levels of SLS (0% and 1%, w/w) and MgSt (0.5% and 1.75%, w/w), along with three different manufacturing processes (direct compression, high-shear wet granulation, and dry granulation). The tablets were compressed to the same solid fraction (0.9) and the resulting tablet hardness values were found to vary over a range of 13-42 SCU, highlighting large compactability differences among these batches. Increase in the level of SLS or MgSt in the formulation had a significant negative effect on compactability and the performance of film-coated tablets. The detrimental effects on compaction and coating performance were magnified for the dry granulation process, likely due to the overall increased shear experienced by excipients (SLS, MgSt, microcrystalline cellulose) during the roller compaction and milling steps. The findings of this study highlight the importance of the manufacturing process when considering the use-level of formulation components such as SLS and MgSt in the formulation.
本研究的目的是确定辅料成分（月桂醇硫酸酯钠：SLS，和硬脂酸镁：MgSt）的水平以及制造工艺对最终混合物料的压缩特性和片剂包衣过程中性能的影响。进行了一项2×2×3析因研究，涉及SLS的两个水平（0%和1%，w/w）和MgSt的两个水平（0.5%和1.75%，w/w），以及三种不同的制造工艺（直接压片、高剪切湿法制粒和干法制粒）。将片剂压制成相同的固体分数（0.9），发现所得片剂的硬度值在13 - 42 SCU范围内变化，突出了这些批次之间较大的可压缩性差异。制剂中SLS或MgSt水平的增加对可压缩性和薄膜包衣片剂的性能有显著的负面影响。对于干法制粒工艺，对压缩和包衣性能的有害影响会放大，这可能是由于辅料（SLS、MgSt、微晶纤维素）在滚压和研磨步骤中总体上受到的剪切增加。本研究的结果突出了在考虑制剂中SLS和MgSt等辅料成分的使用水平时制造工艺的重要性。
