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Updated: Jan 10, 2026

A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Tristearin and C12-18 saturated fatty acids blends: Interplay between eutectic phase behaviour and polymorphic
Serena Bertoni1, Elena Simone2, Beatrice Albertini1
1Department of Pharmacy and Biotechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
Abstract:
This study explores the impact of free fatty acids (FAs) with varying chain lengths (C12-C18) on the crystallization behaviour, crystal structure and polymorphic stability of tristearin (SSS), a long-chain saturated triacylglycerol (TAG). SSS-based blends containing different FAs were crystallized into spherical microparticles, and their solid-state organization was investigated using polarized light microscopy, differential scanning calorimetry, and high-resolution synchrotron small and wide-angle X-ray scattering. We found that the α-polymorph of SSS is miscible with up to 10 wt% of chain-length-matched FAs (C18), forming a solid solution characterized by a single lamellar phase with d-spacing similar to pure α-SSS. As the chain length mismatch increases (C12 > C14 > C16), miscibility with SSS decreased. Time-resolved SAXS revealed a direct correlation between the degree of SSS/FA miscibility and the kinetics of the α-to-β polymorphic transition in SSS. Lauric acid (LA, C12) exhibited immiscible monotectic behaviour with β-SSS and only partially miscible eutectic behaviour with α-SSS, with LA solubility limit in α-SSS between 2.5 and 5 %. In α-SSS/LA blends, aging led to reduced α-SSS crystallite size and a progressive increase in the thickness of the FA-rich phase, while d-spacing remains unchanged. The accelerated α → β polymorphic conversion is attributed to a possible interplay of factors: thermodynamic changes in SSS polymorph stability due to partial miscibility with the FA as well as factors arising from eutectic phase behaviour: reduced crystallite size (microstructural effect) and lattice defects introduced by LA incorporation (molecular-level effect). Overall, this work provides the first experimental evidence linking the eutectic phase behaviour of solid TAG-based mixtures with the kinetic of polymorphic transitions, offering new insights into the structural dynamics and long-term stability of complex fat systems.
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