Effect of Solvent Composition on Crystallization Process of Ascorbic Acid

Abstract

The crystal growth kinetics of ascorbic acid in water and in the solvent systems water/ethanol, water/methanol, and water/ propanol is determined by means of seeded isothermal batch crystallization experiments. The measurements are correlated by a power low equation of the form (G = k g r n ). The composition of the solvent system is found to have a significant influence on the kinetic parameters of growth of ascorbic acid. An increase in growth rate in the presence of alcoholic solvents (20 wt %) is measured compared to experiments with pure water. The thermodynamic effect of the solvent on the growth kinetics is approached by the UNIFAC method. The kinetic effect of solvent composition is explained using the two-step model. Both thermodynamic and kinetic analyses give the same result: The addition of alcoholic solvents (20 wt % ethanol, methanol, and propanol) to the ascorbic acid/water system slightly reduces the diffusion rate and significantly accelerates the surface integration process.

Solubility Determination and Correlation of Warfarin Sodium 2-Propanol Solvate in Pure, Binary, and Ternary Solvent Mixtures

“…Moreover, there is no account correlating WS·IPA solubility and solvent composition, which are fundamental parameters needed to engineer an antisolvent cooling crystallization process for this or other compounds . The selection of the crystallization solvent also affects nucleation and growth kinetics, crystal morphology, and structure − that in turn influence the physicochemical properties of the active pharmaceutical ingredient and its performance. , Hence, the present study focuses on the determination of the solubility of WS·IPA in four pure solvents (acetone, ethanol, IPA, and water), five binary mixtures (IPA + acetone, IPA + ethanol, IPA + water, IPA + heptane, and IPA + hexane), and five ternary mixtures (IPA + acetone + heptane, IPA + acetone + hexane, IPA + ethanol + heptane, IPA + ethanol + hexane, and IPA + water + heptane) at temperatures ranging from 278.15 to 333.15 K using the polythermal method in a Crystal16 multiple reactor system. ,,,− The solvents are categorized as class 3 by the Food and Drug Administration (less toxic and lower risks to human health) except hexane, which is a class 2 solvent . However, hexane is commonly used as an antisolvent in pharmaceutical crystallization processes. ,, The experimental solubility data were correlated employing the modified Apelblat and λh model equations, which enable the interpolation and extrapolation of the determined solubility, providing a better understanding of the solubility profile for WS·IPA.…”

Custom-Built Miniature Continuous Crystallization System with Pressure-Driven Suspension Transfer

“…It shows that different particle size distribution can be obtained by splitting the addition of antisolvent. APIs often have different nucleation and growth rate under different antisolvent composition. , The multistage MSMPR system takes advantage of such features and can generate crystals of different sizes.…”

“…APIs often have different nucleation and growth rate under different antisolvent composition. 29,30 The multi-stage MSMPR system takes advantage of such features, and can generate crystals of different sizes. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Both sets of experiments show that steady state mother liquor concentration is reached within two mean residence time of operation, and that the mother liquor concentration is close to azithromycin solubility at that solvent composition.…”

“…APIs often have different nucleation and growth rate under different antisolvent composition. 29,30 The multistage MSMPR system takes advantage of such features and can generate crystals of different sizes.…”

Continuous Mass Crystallization of Vitamin C in l(+)-Ascorbic Acid−Ethanol−Water System: Size-Independent Growth Kinetic Model Approach

“…The required chemical purity of postsynthesis vitamin C can result from multistage batch crystallization from its water solutions. − Reduction in the necessary batch crystallization stages favoring improvement in the process yield and product crystal quality can be achieved by the introduction into the process system some third component responsible for modification of the intrinsic physicochemical properties of the multicomponent system, mainly solubility with respect to the original solvent. Considering the most advantageous final effects, methanol or ethanol is especially recommended as additive. − Batch crystallization of vitamin C in four-component mixtures, LAA−methanol−ethanol−water, − also provided promising results.…”