361247 Excipient-Process Interactions and Their Effects on Tablet Compaction and Film Coating

Wednesday, November 19, 2014: 2:35 PM
203 (Hilton Atlanta)
Preetanshu Pandey, Shruti Gour, Dilbir Bindra, Jade Trinh, David Buckley and Sherif Badawy, Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, NJ

When formulating drugs with low aqueous solubility and high sticking tendency, it is a common practice to include sodium lauryl sulfate (surfactant) and magnesium stearate (lubricant) in the formulation. Even though sodium lauryl sulfate has some lubricant properties, it is not as effective as magnesium stearate and therefore these excipients may be present together in a given formulation. The objective of this study was to establish the main effects and interactions of sodium lauryl sulfate, and magnesium stearate, and the manufacturing process on final blend compaction properties and the performance of the resultant tablets during film coating. A full factorial study (12 batches) was conducted using 2 levels each of sodium lauryl sulfate (0, 1% w/w) and magnesium stearate (0.5, 1.75% w/w), along with three different manufacturing processes (direct compression, high-shear wet granulation, and dry granulation). Compaction profiles were generated using Stylcam® compaction simulator. At a tablet solid fraction of 0.9 the resulting tablet hardness values were found to vary in the range of 13-42 SCU, highlighting their compactability differences. Both sodium lauryl sulfate and magnesium stearate had a significant negative effect on compaction likely due to the lubricant properties of both these excipients. Additionally, during film coating of these batches logo bridging tablet defects were observed for cases when either sodium lauryl sulfate and/or magnesium stearate was present at the higher concentrations. The negative effects on compaction and coating performance were magnified for the dry granulation process likely due to the overall increased shear experienced by these excipients during the dry granulation process, which in turn increases the ‘effective concentration’ of these excipients. A low level of MgSt (0.5% w/w) with no SLS present showed good compaction and no logo bridging across all manufacturing processes. The findings from this study highlight the importance of the manufacturing process when considering the use-level of excipients such as sodium lauryl sulfate and magnesium stearate in the formulation.

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