Solubility of Diclofenac Acid Form from Solid Dispersions

Krasnyuk, I. I.; Ovsyannikova, L. V.; Nikulina, O. I.; Belyatskaya, A. V.; Kharitonov, Yu. Ya.; Grikh, V. V.; Korol, L. A.; Obidchenko, Yu. A.; Воробьев, А. Н.

doi:10.1007/s11094-015-1183-2

Cited by 7 publications

(1 citation statement)

References 2 publications

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“…Till now, different modifications have been introduced for this purpose, e.g. salt formation, 7,21,[24][25][26][27] co-crystallization, 28 ionic liquid formation, 29 and also nanosuspension 30 and solid dispersion 31 formulations.…”

Section: Introductionmentioning

confidence: 99%

Solvation of diclofenac in water from atomistic molecular dynamics simulations – interplay between solute–solute and solute–solvent interactions

Kozłowska

Rodziewicz

Utesch

et al. 2018

Phys. Chem. Chem. Phys.

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The solubility-permeability relationship of active pharmaceutical ingredients determines the efficacy of their usage. Diclofenac (DCL), which is a widely used nonsteroidal anti-inflammatory drug, is characterized by extremely good membrane permeability, but low water solubility limiting drug effectiveness. The present research focuses on the fundamental explanation of this limitation using the combination of ab initio and classical molecular dynamics simulations of different ionic forms of DCL in water, namely, ionized, un-ionized and the mixture of them both. The analysis of diclofenac solvation in an aqueous environment is used to understand the origin of drug precipitation, especially in gastric pH. The used computational approach reveals the formation of micelle-like self-associated aggregates of diclofenac in water as the result of intermolecular π-π interactions and C-Hπ hydrogen bonds. The DCL aggregation in water is shown to depend mostly on drug concentration, protonation and temperature of the aqueous environment. The detected self-association properties of the drug in water are likely to be of great importance during the development of new drug formulations and fabrication of drug adsorbents for wastewater.

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