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Updated: Jun 23, 2026

A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Aging and metastability of monoglycerides in hydrophobic solutions
1Cavendish Laboratory, University of Cambridge, J J Thomson Avenue, Cambridge CB3 0HE, United Kingdom.
Abstract:
Monoglyceride dispersed in oil acts as gel emulsifier to stabilize ordered lamellar structures; however, with time these phases age, leading to separation of oil and lipid. The aging of aggregated structures of monoglycerides in hydrophobic medium is described by a set of different techniques. Polarized microscopy was used to study the mesomorphic behavior as a function of time. Differential scanning calorimetry was utilized to quantitatively monitor changes in the latent heat in different phase transformations that take place in the aging system. The X-ray diffraction patterns fingerprinted the molecular arrangement in different emerging phases. Infrared spectroscopy was used to monitor the states of hydrogen bonding in the system. We conclude that in both inverted-lamellar and sub-alpha crystalline phases, monoglyceride molecules inevitably lose their emulsified ability in the hydrophobic solutions through the gradual change in hydrogen bonding patterns. On aging, the recombination of hydrogen bonding between glycerol groups causes the segregation of chiral (d and l) isomers within the bilayers. Therefore, all structures were eventually forced to reorder into the ground-state beta-crystalline phase. Accordingly, the highly ordered packing of aged structures weakened the emulsifying ability and finally led to the collapse of the percolating gel network.
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