(M1230-10-56) Sodium Stearyl Fumarate vs. Magnesium Stearate: Understanding the Mechanism of Over-Lubrication

Purpose: Lubricants are critical excipients in the tablet development. They are added to tableting powders to reduce the friction between powder and dies during tableting process reducing in that way tableting failures and damages on the equipment. Moreover, optimizing the powder lubrication helps to produce tablets and capsules with the target characteristics like breaking force, disintegration etc. The right selection of lubricant type and dosage is essential to have a robust manufacturing process^1,2. Magnesium stearate (Mg-St), the most commonly used tableting lubricant nowadays, is known to cause tablet softening and prolonged disintegration time due to the formation of a continuous fatty layer around the particles during the powder blending - the so called over-lubrication^1,3,4. Sodium stearyl fumarate (SSF), often recommended as alternative lubricant to Mg-St, demonstrates less tendency of over-lubrication and negative effect on the tablet characteristics. The present work describes a novel method to understand the differences between magnesium stearate and sodium stearyl fumarate in over-lubrication comparative study by using particle adsorption on glass beads.

Methods: Magnesium stearate (Mg-St) from Taihei Chemical Industrial, Japan and sodium stearyl fumarate (SSF, NISSO SSF) from Nippon Soda, Japan were used. Glass beads with size in 1mm from Taiyo Company, Japan were used to mimic powder granules. Both lubricants were blended for 5, 10-, 20-, 30-, and 60-seconds using Vortex mixer (Vortex-GENIE2, Scientific Industries, Inc., USA). Then, the beads with lubricants were analyzed by Scanning Electron Microscope (SEM, JSM-7900F, JEOL, Japan) and Energy Dispersive Spectrometer (EDS, UltimMax100, Oxford Instruments, UK)².

Results: Figure 1 shows SSF and Mg-St particles adsorption after 60 seconds blending on the surface of the glass beads using SEM/EDS: carbon with origin SSF or Mg-St (in yellow) could be easily distinguished from the silicon from glass (in blue). The building of a continuous film around the beads was observed with magnesium stearate while the SSF pictures showed a moderate particle layering (Figure 1). The impact of the blending time was investigated by blending the lubricants with the glass beads for 5-, 10-, 20-, 30-, and 60-seconds taking SEM/EDS pictures after every blending time. The measurements revealed that, the SSF particle adsorption is less sensitive to the blending time compared to Mg-St. The building of a continuous magnesium stearate layer with increased blending time was visible. NISSO SSF demonstrated a homogeneous distribution on the bead surface without to build a negative continuous film (Figure 2). This speaks for good lubrication properties with very low over-lubrication risk.

Conclusion: The method used in this study showed that NISSO SSF demonstrates much lower tendency of over-lubrication compared to magnesium stearate, keeping at the same time it’s very good lubrication properties: no continuous film building was observed with SSF even at longer blending time.

References: [1] D. Shibata et.al, Application and evaluation of sucrose fatty acid esters as lubricants in the production of pharmaceuticals, J. Pharm. Sci. Technol. Jpn. 62 (2002) 133–145.
[2] Puckhaber, Daniel et al, Prediction of the impact of lubrication on tablet compatibility, International Journal of Pharmaceutics 617 (2022) 121557.
[3] Takeaki Uchimoto et al, A comparative study of glycerin fatty acid ester and magnesium stearate on the dissolution of acetaminophen tablets using the analysis of available surface area, European Journal of Pharmaceutics and Biopharmaceutics 78 (2011) 492–498.
[4] Hiroyuki Abe et al, Effects of lubricant-mixing time on prolongation of dissolution time and its prediction by measuring near infrared spectra from tablets, Drug Development and Industrial Pharmacy, Vol. 38, 2012 - Issue 4.

Figure 1. SEM/EDS photographs of the treated surface of glass beads with various lubricants for 60 seconds. NISSO SSF (a) and Mg-St (b).

Figure 2. SEM/EDS photographs of the treated surface of glass beads with various lubricants for 5, 10, 20, 30 and 60 seconds. NISSO SSF (a) and Mg-St (b). Photographs are overlapped by C (Yellow) / Na or Mg (Red) / Si (Blue).