Revealing solubility-driven instability of triamcinolone acetonide with chiral local anesthetics in binary bulk admixtures

Ratih, Ratih and Wisunaga, Graciella and Charlex, Evelyn and Setiawan, Vendra and Azminah, Azminah and Setiawan, Eko (2026) Revealing solubility-driven instability of triamcinolone acetonide with chiral local anesthetics in binary bulk admixtures. Acta Chromatographica. ISSN 2083-5736

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Abstract

Binary admixtures of the poorly water-soluble chiral corticosteroid triamcinolone acetonide and chiral local anesthetics can be physically unstable in aqueous systems, posing challenges for the accurate stability monitoring. A robust HPLC method was developed to simultaneously evaluate drug stability and the reliability of triamcinolone acetonide quantification in binary admixtures. Under achiral (isotropic) separation conditions, the chromatographic behavior was strongly influenced by the final water–methanol composition. Increasing the methanol improved triamcinolone acetonide solubility and reduced retention. However, it also caused earlier elution of the local anesthetics, leading to overlap with the unretained solvent peak and diminished resolution. Conversely, higher water content impaired peak symmetry, baseline quality, and analyte recovery. Microscopic analysis revealed the onset of physical instability of triamcinolone acetonide within 1 h after bulk admixture preparation, whereas a significant decrease in analyte concentration was detected chromatographically only after 3 h. These findings indicate that physical instability precedes measurable chromatographic loss, supporting microscopy as an early indicator of admixture instability. The physicochemical behavior was elucidated using molecular descriptor analysis (pKa, logP, logS) and in silico docking (AutoDock Vina). Descriptor evaluation found a mismatch between the chromatographic pH (3.0) and the ionization states, while docking confirmed the absence of energetically favorable drug-drug interactions. These findings demonstrate that instability is primarily driven by solubility-mediated precipitation of triamcinolone acetonide rather than specific drug-drug interactions or chirality-related effects. Practically, methanol–water admixtures require to be analyzed immediately or within 1 h after preparation to ensure assay reliability. The integration of chromatographic, microscopic, and computational approaches provides a rational strategy for evaluating corticosteroid–chiral local anesthetic dmixtures.

Item Type:	Article
Subjects:	Q Science > QD Chemistry
Divisions:	Faculty of Pharmacy > Department of Pharmacy
Depositing User:	RATIH
Date Deposited:	13 Oct 2026 09:31
Last Modified:	14 Oct 2026 08:39
URI:	http://repository.ubaya.ac.id/id/eprint/51364

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