Characterization of Synthesized and Commercial Forms of Magnesium Stearate Using Differential Scanning Calorimetry, Thermogravimetric Analysis, Powder X-Ray Diffraction, and Solid-State NMR Spectroscopy.
Magnesium stearate is the salt of a complex mixture of fatty acids, with the majority being stearate and palmitate. It has multiple crystalline forms and, potentially, an amorphous form. Magnesium stearate is used in the pharmaceutical manufacturing industry as a powder lubricant, and typically is added at low levels (∼1%) during the manufacturing process and blended for a relatively short time (∼5 min). Proper levels and mixing times are needed, as too short a mixing time or too small a quantity will result in improper lubrication, and too much can negatively impact dissolution rates. The complex mixture of multiple fatty acids and crystalline forms in magnesium stearate leads to variability between commercial sources, and switching between sources can impact both the amount of lubricant and mixing time needed for proper lubrication. In order to better understand the complex nature of magnesium stearate, a variety of analytical techniques were used to characterize both synthesized and commercial magnesium stearate samples. The results show that correlation among differential scanning calorimetry, thermogravimetric analysis, solid-state NMR spectroscopy, and other techniques provides a unique insight into the forms of magnesium stearate. Finally, the ability to monitor form changes of magnesium stearate in an intact tablet using solid-state NMR spectroscopy is shown.
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536.
Sean P
SP
Delaney
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536; Kansas Analytical Services, LLC, Fort Collins, Colorado 80526.
Matthew J
MJ
Nethercott
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536.
Christopher J
CJ
Mays
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536.
Nickolas T
NT
Winquist
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536.
Donia
D
Arthur
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536.
Julie L
JL
Calahan
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536.
Manish
M
Sethi
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536.
Daniel S
DS
Pardue
College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109.
Junghyun
J
Kim
College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109.
Gregory
G
Amidon
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536. Electronic address: eric.munson@uky.edu.
Eric J
EJ
Munson
D002152:Calorimetry, Differential Scanning; D054327:Lubricants / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D033362:Powder Diffraction; D013229:Stearic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D013607:Tablets; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D054327:Lubricants; D013229:Stearic Acids; D013607:Tablets; C031183:stearic acid
excipients; formulation; hydrates/solvates; physical characterization; solid-state NMR; spectroscopy; tableting