Fellowship: Julie Calahan: Correlating magnesium stearate physicochemical properties with functional properties

Magnesium stearate (MgSt) is commonly used as a lubricant excipient and is present in about half of all pharmaceutical tablet formulations. However, many formulation labs using MgSt have reported batch-to-batch variability and inconsistent lubrication and dissolution results. The variable performance of different MgSt commercial lots has been recognized and the properties have been studied since the 1970s, but there are several complications with studying MgSt. The anhydrate, monohydrate, dihydrate and trihydrate forms have been identified and the solid forms characterized by various techniques including X-ray diffraction, thermal analysis, vapor sorption, particle size and specific surface area. However, there is no agreement on the best identification method to differentiate between MgSt hydrate forms. Correlations between MgSt properties with dissolution and lubrication have been studied, but because there has not been a reliable method for determining hydrate form, interpreting the results is complicated. Recently, solid-state NMR spectroscopy (SSNMR) has been used to characterize both pure forms and commercial lots of MgSt. The hydrate forms are clearly identified with 13C SSNMR, with mixtures of forms and commercial materials being easily identified, as shown by Delaney et al. The hypothesis of this research work is that the observed batch-to-batch variability observed in formulations containing MgSt can be correlated with differences in MgSt physicochemical properties, i.e. hydrate form, fatty acid salt composition and particle size. The primary goal of the proposed research is to understand the properties of MgSt hydrate forms and how they affect the functional properties of MgSt in tablet formulations.