Solubility of Artemisinin in Different Single and Binary Solvent Mixtures Between (284.15 and 323.15) K and NRTL Interaction Parameters

Nti-Gyabaah, Joseph; Gbewonyo, Kodzo; Chiew, Yee C.

doi:10.1021/je100125x

Cited by 38 publications

(38 citation statements)

References 20 publications

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“…The local composition models are widely applied to calculate the fugacity coefficients of solute in the solid−liquid equilibrium. A general simplified equation, which can be deduced from literature, 10 is described in eq 4.…”

Section: λHmentioning

confidence: 99%

Thermodynamic Properties of Form A and Form B of Florfenicol

Sun

Hao

Xie

et al. 2014

Ind. Eng. Chem. Res.

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In this research, a new polymorph of florfenicol (form B) was discovered and successfully prepared. The new polymorph was characterized and identified by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) techniques. It was found that form A has lower melting temperature while higher fusion enthalpy. The solubility of both florfenicol polymorphs in methanol, 2-propanol, acetone, acetonitrile, ethanol, and ethyl acetate were experimentally determined from 278.15 to 318.15 K with a dynamic method. For all tested solvents, the solubility data of florfenicol form B are higher than those of form A. The modified Apelblat model, the NRTL model, and the λh model were adopted to calculate the solubility of florfenicol two forms with satisfactory correlation results. In addition, the dissolution thermodynamic properties of florfenicol form A and form B, including dissolution enthalpy, dissolution entropy, and Gibb's dissolution energy in all tested solvents, were obtained. Combining the results of DCS determination, the solubility, and all the dissolution thermodynamic data, it was confirmed that florfenicol polymorph A and polymorph B belong to the enantiotropic polymorph system.

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Section: λHmentioning

confidence: 99%

Thermodynamic Properties of Form A and Form B of Florfenicol

Sun

Hao

Xie

et al. 2014

Ind. Eng. Chem. Res.

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“…The present work explicitly estimates solubilities using the original NRTL model, 31,32 for which all required interaction parameters can be determined on the basis of published literature. 34,35 Here, the solubility of species i, x i , is computed from the ideal solubility, x i id , and the activity coefficient γ i (equation 8). The ideal solubility (at temperature T) is estimated from the enthalpy of fusion ΔH fus ; the average difference in heat capacity (ΔC p ) between the temperature and the API melting point, T fus , assumed to be 77.2 J mol -1 K -1 in equation 9; 34 and R, the universal gas constant.…”

Section: Nrtl Solubility Modellingmentioning

confidence: 99%

“…34,35 Here, the solubility of species i, x i , is computed from the ideal solubility, x i id , and the activity coefficient γ i (equation 8). The ideal solubility (at temperature T) is estimated from the enthalpy of fusion ΔH fus ; the average difference in heat capacity (ΔC p ) between the temperature and the API melting point, T fus , assumed to be 77.2 J mol -1 K -1 in equation 9; 34 and R, the universal gas constant. In the NRTL method, the activity coefficient of species i in a n-component mixture, γ i , is given by equation 10.…”

Section: Nrtl Solubility Modellingmentioning

confidence: 99%

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Nonlinear Optimization via Explicit NRTL Model Solubility Prediction for Antisolvent Mixture Selection in Artemisinin Crystallization

Jolliffe

Diab

Gerogiorgis

2017

Org. Process Res. Dev.

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Continuous Pharmaceutical Manufacturing (CPM) has the potential to revolutionise the pharmaceutical industry, with many expected benefits in terms of cost, efficiency and quality. Process modelling and optimisation are valuable methodologies for comparative technoeconomic evaluations: this paper pursues total upstream CPM cost minimisation via two nonlinear optimisation methods. An explicit NRTL solubility estimation method has been used in order to analyse the potential performance of three binary antisolvent mixtures for the crystallisation of artemisinin. This Active Pharmaceutical Ingredient (API) is a key antimalarial substance and has been the focus of several CPM studies, including continuous chemistry and separation. Ethanol, acetone and ethyl acetate are the three antisolvents studied. Used as a binary antisolvent with toluene as the solvent, the composition of the binary antisolvent, the quantity of the binary antisolvent with respect to the process solvent, and the temperature the overall mixture is cooled to in the crystallisation process are formulated as the three key variables in a nonlinear optimisation problem. Two solvers are used, NOMAD and NLOPT-BOBYQA. Results show that they have very similar precision (<1 % difference), but that the latter is up to 66 % faster; NLOPT-BOBYQA was used for the majority of optimisation cases. Results show that for the size of the temperature gradient of the crystallisation has a much stronger effect on the total cost than the quantity of antisolvent used. Nearly pure antisolvent use (ethyl acetate followed by ethanol) is favoured as yielding the lowest total cost (for a single crystalliser). Considering multiple units, results indicate that higher API recovery, E-factor, and OpEx benefits can be achieved when using two crystallisers, but metrics are inferior with three or more. For sequential crystallisers of varying size, increasing the number of crystallisers also benefits OpEx, E-factor, and API recovery, but CapEx continues to increase, thereby promising technical but no economic benefits.

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“…Solvent Screening for Crystallization. Due to the available solubility data of artemisinin in toluene and ethanol, 32 the application of toluene as the reaction medium, and the possibility to apply ethanol as a strong solvent in gradient chromatography (Section 3.3), preliminary screening of the corresponding binary solvent mixtures was performed to select a suitable solvent for crystallization. Since the artemisinin solubility in pure toluene is rather high, and toluene is considered as a class 2 solvent, we decided to use a solvent mixture with toluene as minor component, and ethanol as a major component.…”

Section: Characterization Of Reactor Effluent Andmentioning

confidence: 99%

Recovery of Artemisinin from a Complex Reaction Mixture Using Continuous Chromatography and Crystallization

Horosanskaia

Lee

Lorenz

et al. 2015

Org. Process Res. Dev.

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Artemisinin, a secondary metabolite of sweet wormwood, is the basis for the production of the most effective antimalarial drugs. Since the amount of artemisinin currently produced from plants is not sufficient to treat the worldwide malaria cases, an effective semisynthetic method was developed recently that is capable of producing artemisinin from dihydroartemisinic acid (DHAA). DHAA is a byproduct obtained during the extraction of artemisinin from plant leaves. The photocatalytic reaction to convert DHAA to artemisinin can be performed continuously in a tubular reactor using toluene as a solvent. The reactor effluent contains besides artemisinin the photocatalyst (dicyanoanthracene) and several compounds that are structurally similar to artemisinin, including unreacted DHAA starting material. To isolate artemisinin from the reaction mixture, two separation techniques were applied, crystallization and chromatography. The solid obtained by seeded cooling crystallization was highly enriched in artemisinin but contained also traces of the photocatalyst. In contrast, using a variant of continuously operated multicolumn simulated moving bed (SMB) chromatography, which splits the feed into three fractions, we were able to recover efficiently the photocatalyst in the raffinate stream. The extract stream provided already almost pure artemisinin, which could be finally further purified in a simple crystallization step

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Solubility of Artemisinin in Different Single and Binary Solvent Mixtures Between (284.15 and 323.15) K and NRTL Interaction Parameters

Cited by 38 publications

References 20 publications

Thermodynamic Properties of Form A and Form B of Florfenicol

Thermodynamic Properties of Form A and Form B of Florfenicol

Nonlinear Optimization via Explicit NRTL Model Solubility Prediction for Antisolvent Mixture Selection in Artemisinin Crystallization

Recovery of Artemisinin from a Complex Reaction Mixture Using Continuous Chromatography and Crystallization

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