TY - JOUR
T1 - Deciphering magnesium stearate thermotropic behavior
AU - Haware, Rahul V.
AU - Vinjamuri, Bhavani Prasad
AU - Sarkar, Amrita
AU - Stefik, Morgan
AU - Stagner, William C.
N1 - Funding Information:
RVH, BPV, and WCS thank the Research Triangle Nanotechnology Network (RTNN) for a grant to use the SAXS equipment for the initial proof-of-concept studies. The authors acknowledge the use of the Shared Materials Instrumentation Facility (SMIF) at Duke University, and support for these activities from the RTNN (NSF award ECCS-1542015). Any opinions, findings, and conclusions or recommendations expressed in this work are those of the authors and do not necessarily reflect the views of the NSF, or Duke University, NC. The authors also thank Ms. Tanvi Joshi from Campbell University for assistance in performing some of the thermal and SAXS studies.
Funding Information:
This work made use of the South Carolina SAXS Collaborative (SCSC), supported by the National Science Foundation ( NSF ) Major Research Instrumentation program ( DMR - 1428620 ). MS thanks University of South Carolina for startup funds and AS thanks the Leon Schechter Endowed Fellowship for Polymer Nanocomposites.
Funding Information:
RVH, BPV, and WCS thank the Research Triangle Nanotechnology Network (RTNN) for a grant to use the SAXS equipment for the initial proof-of-concept studies. The authors acknowledge the use of the Shared Materials Instrumentation Facility (SMIF) at Duke University, and support for these activities from the RTNN ( NSF award ECCS - 1542015 ). Any opinions, findings, and conclusions or recommendations expressed in this work are those of the authors and do not necessarily reflect the views of the NSF , or Duke University, NC. The authors also thank Ms. Tanvi Joshi from Campbell University for assistance in performing some of the thermal and SAXS studies.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/9/5
Y1 - 2018/9/5
N2 - Magnesium stearate (MgSt) is the most commonly used excipient for oral solid dosage forms, yet there is significant commercial physicochemical variability that can lead to variable performance of critical product attributes. Differential scanning calorimetry (DSC) is often used as a quality control tool to characterize MgSt, but little data is available regarding the physicochemical relevance for the DSC thermograms. The main aim of this study was to decipher MgSt's complex thermotropic behavior using DSC, thermogravimetric analysis, capillary melting point, polarized hot-stage microscopy, and temperature dependent small-angle X-ray scattering (SAXS) and assign physicochemical relevance to the DSC thermograms. Several DSC thermal transitions are irreversible after the first heating cycle of a heat-cool-heat-cool-heat cycle. Interestingly, after the first heat cycle, the complex cool-heat-cool-heat DSC thermograms were highly reproducible and exhibited 6 reversible exothermic-endothermic conjugate pairs. SAXS identified 5 distinct mesophases at different temperatures with Phase C′ persisting to 250 °C. MgSt maintained molecular ordering beyond 276 °C and did not undergo a simple melting phenomena reported elsewhere. This research serves as a starting point to design heat-treatment strategies to create more uniform MgSt starting material.
AB - Magnesium stearate (MgSt) is the most commonly used excipient for oral solid dosage forms, yet there is significant commercial physicochemical variability that can lead to variable performance of critical product attributes. Differential scanning calorimetry (DSC) is often used as a quality control tool to characterize MgSt, but little data is available regarding the physicochemical relevance for the DSC thermograms. The main aim of this study was to decipher MgSt's complex thermotropic behavior using DSC, thermogravimetric analysis, capillary melting point, polarized hot-stage microscopy, and temperature dependent small-angle X-ray scattering (SAXS) and assign physicochemical relevance to the DSC thermograms. Several DSC thermal transitions are irreversible after the first heating cycle of a heat-cool-heat-cool-heat cycle. Interestingly, after the first heat cycle, the complex cool-heat-cool-heat DSC thermograms were highly reproducible and exhibited 6 reversible exothermic-endothermic conjugate pairs. SAXS identified 5 distinct mesophases at different temperatures with Phase C′ persisting to 250 °C. MgSt maintained molecular ordering beyond 276 °C and did not undergo a simple melting phenomena reported elsewhere. This research serves as a starting point to design heat-treatment strategies to create more uniform MgSt starting material.
KW - Magnesium stearate mesophases
KW - Temperature dependent small angle X-ray scattering (SAXS)
KW - Thermal analysis
KW - Thermotropic reversibility
UR - http://www.scopus.com/inward/record.url?scp=85049441948&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2018.07.001
DO - 10.1016/j.ijpharm.2018.07.001
M3 - Article
C2 - 29991451
AN - SCOPUS:85049441948
SN - 0378-5173
VL - 548
SP - 314
EP - 324
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1
ER -