Interplay of Aging and Lot-to-Lot Variability on the Physical and Chemical Properties of Excipients: A Case Study of Mono- and Diglycerides

Abstract

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.

Phase Behavior of Drug–Lipid–Surfactant Ternary Systems toward Understanding the Annealing-Induced Change

“…This change in the polymorphic structure resulted in the formation of smaller/condensed/tight lamellar structures that could be responsible for closed packing of the lipidic crystals upon annealing leading to the expulsion of Kolliphor P 407 out of the lipid microstructures, resulting in the migration of Kolliphor P 407 outward of the formulation. 12,20 4.3. Microscopic Consequence of the Phase Behavior of the Lipid-Surfactant System.…”

“…The established 1 H qNMR method, mentioned in our previous research work, was used for the quantification of different lipid components of Compritol such as mono-, di-, and triglycerides, and positional isomers of C22 saturated fatty acids (1-MG, 2-MG, 1,3-DG, 1,2-DG, and TG). 20,22 The effect of different concentrations of Kolliphor P 407 on the physical separation of different components of Compritol within formulations was evaluated. Briefly, annealed and unannealed formulations were prepared as mentioned above and washed with distilled water overnight.…”

Crystallization and Rheology of Mono- and Diglycerides and Their Role in Stabilization of Emulsion Droplets in Model Topical Ointments

“…However with age and exposure to high temperatures. 24 The peak for TG is not observed in the NMR spectra, indicating that TG does not crystallize in the experimental temperature range and, therefore, is absent in the separated crystals. The chemical profiling of the type-1 and type-2 crystals using NMR clearly confirms that DG has lower crystallization temperature due to its higher solubility in oil compared to MG.…”

“…7−21 MDGs are produced by esterification of glycerol and fatty acids at high temperatures. 22,23 As per the USP-NF, MDGs are mixtures of monoglycerides (MG), diglycerides (DG), and a small fraction of triglycerides (TG), containing not less than 40% of MG. 24 A commercial MDG commonly contains a mixture of glycerides with acyl chains from stearic acid (C 17 H 35 COOH) and palmitic acid (C 15 H 31 COOH). Based on the ester bond position, both mono-and diglycerols can exist as two positional isomers each: 1-monoglycerides (1-MG) and 2monoglycerides (2-MG), and, 1,3-diglycerides (1,3-DG) and 1,2-diglycerides (1,2-DG), respectively.…”

“…Structurally, 2-MG and 1,2-DG are less stable and are prone to transform to the other isomeric forms with age and upon exposure to high temperatures. 24 These heterogeneities of chemical composition and isomers of MDG can cause a differential crystallization behavior in the continuous oil phase and at the interface and could impact physical stability of formulations after manufacturing steps involving melting and cooling. An oil-based topical formulation is typically produced by first dissolving MDG in an oil medium (petrolatum or wax) at a high temperature.…”