To evaluate the effect of various magnesium stearate polymorphs using powder rheology and thermal analysis

Abstract

The effects of magnesium stearate (MgSt) polymorphs—anhydrate (MgSt-A), monohydrate (MgSt-M), and dihydrate (MgSt-D)—on rheological properties of powders were evaluated using techniques such as atomic analysis and powder rheometry. Additional evaluation was conducted using thermal analysis, micromeritics, and tableting forces. In this study, binary ratios of neat MgSt polymorphs were employed as lubricants in powder blends containing acetaminophen (APAP), microcrystalline cellulose (MCC), and lactose monohydrate (LAC-M). Powder rheometry was studied using permeability, basic flow energy (BFE), density, and porosity analysis. Thermal conductivity and differential scanning calorimetric analysis of MgSt polymorphs were employed to elucidate MgSt effect on powder blends. The impact of MgSt polymorphs on compaction characteristics were analyzed via tablet compression forces. Finally, the distribution of atomized magnesium (Mg) ions as a function of intensity was evaluated using laser-induced breakdown spectroscopy (LIBS) on tablets. The results from LIBS analysis indicated the dependency of the MgSt polymorphic forms on the atomized Mg ion intensity, with higher Mg ion intensity suggesting higher lubricity index (i.e. greater propensity to over-lubricate). The results from lubricity index suggested the tendency of blends to over-lubricate based on the MgSt polymorphic forms. Finally, tableting forces suggested that MgSt-D and MgSt-A offered processing benefits such as lower ejection and compression forces, and that MgSt-M showed the most stable compression force in single or combined polymorphic ratios. These results suggested that the initial moisture content, crystal arrangement, intra- and inter-molecular packing of the polymorphs defined their effects on the rheology of lubricated powders.

Keywords::

• Polymorph
• tableting
• rheology
• lubricant
• magnesium stearate
• thermal analysis
• anhydrous
• dihydrate
• monohydrate

Acknowledgement

The authors wish to acknowledge Dr. Gary Nichols and Mr. Dan Ramlose at Covidien for providing analytical support and helpful discussion. Additional acknowledgement to Natoli Engineering, Freeman Technologies, C-Therm Technologies, and Pharmalaser Inc., for their technical and instrument support.

Declaration of interest

The authors report no conflicts of interest.