TY - JOUR
T1 - Interplay of Aging and Lot-to-Lot Variability on the Physical and Chemical Properties of Excipients
T2 - A Case Study of Mono- And Diglycerides
AU - Kushwah, Varun
AU - Saraf, Isha
AU - Yeoh, Thean
AU - Ardelean, Ioan
AU - Weber, Hansjoerg
AU - Sarkar, Avik
AU - Chen, Raymond
AU - Vogel, Trevor
AU - Modhave, Dattatray
AU - Laggner, Peter
AU - Paudel, Amrit
N1 - Publisher Copyright:
©
PY - 2021/3/1
Y1 - 2021/3/1
N2 - The present study investigates the chemical composition governing the physical properties of mono- and diglycerides (MDGs) at the microstructural level, as a function of aging and lot-to-lot variability. The physical structure of the MDG plays a vital role in ameliorating the emulsion stability and is widely explored in diverse research horizons related to the pharmaceutical, cosmetic, and food industries. In an effort to understand the mechanism of emulsion stabilization, physical properties were extensively evaluated in selective commercial lots to determine if there is a correlation between the chemical composition of MDG and physical properties. The solid state of the MDG samples with different aging profiles was characterized using X-ray scattering, differential scanning calorimetry, attenuated total reflection-Fourier transform infrared spectroscopy, and NMR relaxometry. Moreover, the kinetic aspect of solid-state transformation was also evaluated via treating MDG samples with a heat-cool cycle. The chemical composition of MDGs was quantified using a quantitative NMR (qNMR) method. Interestingly, the X-ray scattering results demonstrated a change in the MDG polymorphic form and an increase in the %β content as a function of aging. The increase in the %β content led to the formation of rigid crystal structures of MDG, as evident from the NMR relaxometry. Chemical quantification of isomeric composition revealed chemical composition change as a potentially critical factor responsible for the altered physical structures of MDG with respect to aging and lot-to-lot variability. The findings correlated the solid-state transformation with the change in the chemical composition of the MDG as a combined effect of aging and lot-to-lot variability. This work serves as a basis to better understand the interdependency of the physicochemical properties of MDG. Furthermore, the present work can also be used as guidance for setting up the specifications of MDG, as per the required polymorphic form for a multitude of applications.
AB - The present study investigates the chemical composition governing the physical properties of mono- and diglycerides (MDGs) at the microstructural level, as a function of aging and lot-to-lot variability. The physical structure of the MDG plays a vital role in ameliorating the emulsion stability and is widely explored in diverse research horizons related to the pharmaceutical, cosmetic, and food industries. In an effort to understand the mechanism of emulsion stabilization, physical properties were extensively evaluated in selective commercial lots to determine if there is a correlation between the chemical composition of MDG and physical properties. The solid state of the MDG samples with different aging profiles was characterized using X-ray scattering, differential scanning calorimetry, attenuated total reflection-Fourier transform infrared spectroscopy, and NMR relaxometry. Moreover, the kinetic aspect of solid-state transformation was also evaluated via treating MDG samples with a heat-cool cycle. The chemical composition of MDGs was quantified using a quantitative NMR (qNMR) method. Interestingly, the X-ray scattering results demonstrated a change in the MDG polymorphic form and an increase in the %β content as a function of aging. The increase in the %β content led to the formation of rigid crystal structures of MDG, as evident from the NMR relaxometry. Chemical quantification of isomeric composition revealed chemical composition change as a potentially critical factor responsible for the altered physical structures of MDG with respect to aging and lot-to-lot variability. The findings correlated the solid-state transformation with the change in the chemical composition of the MDG as a combined effect of aging and lot-to-lot variability. This work serves as a basis to better understand the interdependency of the physicochemical properties of MDG. Furthermore, the present work can also be used as guidance for setting up the specifications of MDG, as per the required polymorphic form for a multitude of applications.
KW - aging
KW - chemical composition
KW - emulsifiers
KW - MDG
KW - polymorphism
UR - http://www.scopus.com/inward/record.url?scp=85100256154&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.0c00847
DO - 10.1021/acs.molpharmaceut.0c00847
M3 - Article
C2 - 33475378
AN - SCOPUS:85100256154
SN - 1543-8384
VL - 18
SP - 862
EP - 877
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 3
ER -