Thermodynamic Modeling of Triglycerides using PC-SAFT

Brinkmann, Joscha; Luebbert, Christian; Zaitsau, Dzmitry H.; Verevkin, Sergey P.; Sadowski, Gabriele

doi:10.1021/acs.jced.8b01046

Cited by 15 publications

(22 citation statements)

References 27 publications

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“…Only the solubilities of PZQ in 2-propanol deviate slightly at high temperatures. PZQ was assumed to be an induced-associating component , (the association energy was set to zero and the association volume was set to 0.02).…”

Section: Resultsmentioning

confidence: 99%

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PC-SAFT Modeling of Phase Equilibria Relevant for Lipid-Based Drug Delivery Systems

et al. 2021

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In this work we investigated the solubilities of 10 active pharmaceutical ingredients (APIs), namely, fenofibrate, ibuprofen, cinnarizine, carbamazepine, indomethacin, naproxen, griseofulvin, glibenclamide, felodipine, and praziquantel in the pharmaceutically relevant excipients tricaprylin, Lauroglycol FCC, Capryol 90, Kolliphor TPGS, ethanol, and monolaurin. API solubilities were either determined gravimetrically, with high-performance liquid chromatography, or with differential scanning calorimetry. Mutual solubilities in the three possible mixtures out of Kolliphor TPGS, tricaprylin, and carbitol as well as the vapor sorption of ethanol in tricaprylin were determined experimentally. The Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) pure-component parameters for seven APIs were determined via fitting to vapor pressures and liquid densities or to solubilities in organic solvents. In total, 80 binary interaction parameters were fitted to the investigated binary mixtures. They can be used in the future to improve the accuracy of lipid-based drug delivery systems in-silico screenings with PC-SAFT.

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Section: Resultsmentioning

confidence: 99%

“…The nomenclature of glycerides and carboxylic acids used in this work was adapted from our recent work. 11 The first two letters of the abbreviation describe the kind of component carbon chain. For instance, monolaurin is abbreviated as MG12 0 .…”

Section: Introductionmentioning

confidence: 99%

PC-SAFT Modeling of Phase Equilibria Relevant for Lipid-Based Drug Delivery Systems

et al. 2021

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“…The measured values were then extrapolated to the pure amines. This procedure has already been successfully performed in previous works for different triglycerides . In preliminary tests, DMSO has proven to be a suitable solvent to dissolve the investigated amines in sufficient amounts up to amine mass fractions w amine of 0.2.…”

Section: Resultsmentioning

confidence: 99%

“…This procedure has already been successfully performed in previous works for different triglycerides. 21 In preliminary tests, DMSO has proven to be a suitable solvent to dissolve the investigated amines in sufficient amounts up to amine mass fractions w amine of 0.2. Due to the lower solubility of tyramine in DMSO compared to halostachine and phenylethanolamine, a maximum amine mass fraction of w amine = 0.15 was chosen for tyramine to guarantee a homogeneous liquid during the measurement.…”

Section: ■ Resultsmentioning

confidence: 99%

Thermodynamic Properties of Biogenic Amines and Their Solutions

et al. 2021

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Vapor pressures of the biologically and industrially relevant amines 2-phenylethan-1-amine, 2-amino-1-phenylethanol, α-(methylaminomethyl)benzyl alcohol, 1-phenylmethanamine, and N,N-diethylundecan-1-amine were measured via the transpiration method. Pure-component parameters for the thermodynamic model PC-SAFT were fitted to these vapor pressures and to liquid densities. The pure-component parameters were validated with measured liquid densities of binary mixtures dimethylsulfoxid + 4-(2-aminoethyl)phenol, dimethylsulfoxid + 2-amino-1-phenylethanol, dimethylsulfoxid + α-(methylaminomethyl)benzyl alcohol, and dimethylsulfoxid + 1-phenylmethanamine at 0.102 MPa and temperatures from 298.15 to 343.15 K at different amine mass fractions. Solid−liquid equilibria at 0.1 MPa were measured in binary mixtures of α-(methylaminomethyl)benzyl alcohol + water and 4-(2-aminoethyl)phenol + water at 298.15 and 308.15 K. Finally, the presence of liquid−liquid phase separation for these systems was qualitatively predicted using PC-SAFT based on the solid−liquid equilibria only and validated for the system α-(methylaminomethyl)benzyl alcohol + water by experiments at 293.15 and 323 K at 0.1 MPa.

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“…Tricaprylin (TG8 0 8 0 8 0 ) and carbitol were purchased from Sigma Aldrich (Steinheim, Germany) with purity >99%. The glycerides are abbreviated in this work according to [ 22 ] (e.g. tricaprylin: TG8 0 8 0 8 0 , monolaurin: MG8 0 : The first two letters define the type of component (TG = triglyceride, DG = diglyceride and MG = monoglyceride.…”

Section: Methodsmentioning

confidence: 99%

In-Silico Screening of Lipid-Based Drug Delivery Systems

et al. 2020

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Purpose This work proposes an in-silico screening method for identifying promising formulation candidates in complex lipid-based drug delivery systems (LBDDS). Method The approach is based on a minimum amount of experimental data for API solubilites in single excipients. Intermolecular interactions between APIs and excipients as well as between different excipients were accounted for by the Perturbed-Chain Statistical Associating Fluid Theory. The approach was applied to the in-silico screening of lipid-based formulations for ten model APIs (fenofibrate, ibuprofen, praziquantel, carbamazepine, cinnarizine, felodipine, naproxen, indomethacin, griseofulvin and glibenclamide) in mixtures of up to three out of nine excipients (tricaprylin, Capmul MCM, caprylic acid, Capryol™ 90, Lauroglycol™ FCC, Kolliphor TPGS, polyethylene glycol, carbitol and ethanol). Results For eight out of the ten investigated model APIs, the solubilities in the final formulations could be enhanced by up to 100 times compared to the solubility in pure tricaprylin. Fenofibrate, ibuprofen, praziquantel, carbamazepine are recommended as type I formulations, whereas cinnarizine and felodipine showed a distinctive solubility gain in type II formulations. Increased solubility was found for naproxen and indomethacin in type IIIb and type IV formulations. The solubility of griseofulvin and glibenclamide could be slightly enhanced in type IIIb formulations. The experimental validation agreed very well with the screening results. Conclusion The API solubility individually depends on the choice of excipients. The proposed in-silico-screening approach allows formulators to quickly determine most-appropriate types of lipid-based formulations for a given API with low experimental effort. Graphical abstract

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Thermodynamic Modeling of Triglycerides using PC-SAFT

Cited by 15 publications

References 27 publications

PC-SAFT Modeling of Phase Equilibria Relevant for Lipid-Based Drug Delivery Systems

PC-SAFT Modeling of Phase Equilibria Relevant for Lipid-Based Drug Delivery Systems

Thermodynamic Properties of Biogenic Amines and Their Solutions

In-Silico Screening of Lipid-Based Drug Delivery Systems

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