Challenges in Detecting Magnesium Stearate Distribution in Tablets

Abstract

Abstract. Magnesium stearate (MS) is the most commonly used lubricant in pharmaceutical industry. During blending, MS particles form a thin layer on the surfaces of the excipient and drug particles prohibiting the bonding from forming between the particles. This hydrophobic layer decreases the tensile strength of tablets and prevents water from penetrating into the tablet restraining the disintegration and dissolution of the tablets. Although overlubrication of the powder mass during MS blending is a wellknown problem, the lubricant distribution in tablets has traditionally been challenging to measure. There is currently no adequate analytical method to investigate this phenomenon. In this study, the distribution of MS in microcrystalline cellulose (MCC) tablets was investigated using three different blending scales. The crushing strength of the tablets was used as a secondary response, as its decrease is known to result from the overlubrication. In addition, coating of the MCC particles by MS in intact tablets was detected using Raman microscopic mapping. MS blending was more efficient in larger scales. Raman imaging was successfully applied to characterize MS distribution in MCC tablets despite low concentration of MS. The Raman method can provide highly valuable visual information about the proceeding of the MS blending process. However, the measuring set-up has to be carefully planned to establish reliable and reproducible results.

Characterization of Synthesized and Commercial Forms of Magnesium Stearate Using Differential Scanning Calorimetry, Thermogravimetric Analysis, Powder X-Ray Diffraction, and Solid-State NMR Spectroscopy

“…The most commonly used approaches to study MgSt in formulations is to use SEM to study the potential particles of MgSt produced during mixing. 28,50 Raman Spectroscopy has been used successfully to image MgSt particles to determine their location of MgSt in the powder/tablet. 28 XPS has been used successfully to image the location of the magnesium ions on the surface of tablets.…”

“…19 As mentioned above, multiple studies have focused on obtaining a better understanding of the complexities of MgSt as a lubricant because it was originally discovered as a potential lubricant by Hanssen et al 11 There have been numerous attempts to fully understand MgSt in formulations, [20][21][22][23] including multiple studies using Raman spectroscopy to monitor MgSt in both blends and tablets. [24][25][26][27][28] Raman mapping has proven useful in the visualization of the coating of microcrystalline cellulose particles by MgSt, but quantitative data were not possible with that experimental approach. 28 Many of the investigations have searched for a link between the structure and the functional properties.…”

“…[24][25][26][27][28] Raman mapping has proven useful in the visualization of the coating of microcrystalline cellulose particles by MgSt, but quantitative data were not possible with that experimental approach. 28 Many of the investigations have searched for a link between the structure and the functional properties. [29][30][31] In a study by Leinonen et al, 32 it was discovered that surface area and particle size significantly affect the lubricity between the commercial sources, but reduced lubricity of an MgSt sample prepared using only stearic acid could not be explained.…”

Lubricant sensitivity in function of paddle movement in the forced feeder of a high-speed tablet press

“…[1][2][3][4][5][6] The extent of this effect mainly depends on the magnesium stearate concentration, mixing time and mixing intensity. 2,[7][8][9] During tablet manufacturing, the lubricant concentration and the mixing procedure (type of mixer, mixing time and intensity, mixing order) is mostly well defined, taking into account the possible negative effects of magnesium stearate.…”

The Comparison of Two Challenging Low Dose APIs in a Continuous Direct Compression Process

“…However, the limited accuracy of both SEM imaging and EDS analysis prevented comparison of the formation of an ordered mixture. It might be feasible to use some other techniques, such as Raman spectroscopy [52], in future studies.…”