Excipient-Process Interactions and their Impact on Tablet Compaction and Film Coating

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 x 2 x 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. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3666-3674, 2014