Mamata Mukhopadhyay

Partial molar volume reduction of solvent for solute crystallization using carbon dioxide as antisolvent

Abstract The gas antisolvent crystallization (GASC) process using dense carbon dioxide (CO 2 ) as antisolvent is particularly useful for purification and micronization of thermo-labile bioactive solid substances. Conventionally, the GASC process is characterized by the relative total volume expansion or the relative molar volume expansion of the solution. A new criterion is proposed in this work in terms of the relative partial molar volume reduction (RPMVR) of the solvent for selection of the solvent and the optimum process condition for the GASC process, as it directly gives a measure of the fraction of the dissolved solute crystallized. The solute solubility is proportional to the partial molar volume of the solvent, v 2 which drastically decreases at a high CO 2 dissolution. This is attributed to clustering of CO 2 molecules around the solvent molecules causing the loss of solvent power. This results in the desired antisolvent effect for lowering the solute solubility. v 2 has been calculated for a large number of solvent–CO 2 liquid mixtures using the Peng–Robinson equation of state. It has been observed that v 2 drastically reduces at a high value of x 1 , irrespective of the fact whether the solvent density is higher or lower than that of the CO 2 . The solute solubility has been predicted from its value at the ambient pressure and the ratio of the partial molar volumes of the solvent with and without CO 2 dissolved in it. The predicted solubility of β-carotene in ethyl acetate with variation of x 1 at 298 K has been found to compare well with the experimentally observed trend of the GASC process.

Partial molar volume fraction of solvent in binary (CO2–solvent) solution for solid solubility predictions

Prediction of solid solute solubility in an organic solvent with dissolution of dense CO2 as antisolvent is important for the design of antisolvent crystallization processes. A new model is proposed in this work to predict the mole fraction of a pure solid solute in a ternary (CO2–solvent–solid) system at solid–liquid equilibrium. This is based on the hypothesis that CO2 molecules cluster around the solvent molecules at high values of CO2 mole fraction. As a result the solvent molecules proportionately lose their affinity for the solid solute molecules. Accordingly the solid mole fraction in a solution is considered to be proportional to the partial molar volume fraction (PMVF) of the solvent in the binary (CO2–solvent) liquid solution or the solvents contribution to the molar volume of the binary system. This model enables prediction of the liquid phase composition of the ternary system using only the binary information. The model has been validated, by predicting the solid solubility in various organic solvents, in good agreement with the corresponding experimental data from the literature, for several solids, such as β-carotene, cholesterol, acetaminophen, as well as naphthalene, phenanthrene and salicylic acid. The performance of this model is found to be better than an earlier method, which uses the partial molar volume (PMV) of solvent in the CO2–solvent mixture.

Modeling Solute-co-solvent interactions for supercritical-fluid extraction of fragrances

Abstract Supercritical carbon dioxide extraction of fragrances from jasmine flowers has facilitated higher recovery and better quality product than the conventional hexane extraction. Addition of a polar co-solvent to the CO2 has rendered 200–600% enhancement in the fragrance recovery, the highest being with DMSO, and the lowest with methanol. Acetone enhances the solubility of cis-jasmone by 266% and enriches the product quality by offering the highest dissolution ratio enhancements for m-anthranilate and benzyl acetate, whereas with DMSO the dissolution ratio enhancements are the highest for other important fragrant components. Hence, a combination of the polar functional groups in the co-solvent as or equivalent to those of acetone and DMSO, seems to be most effective. With a view to selecting suitable co-solvents, the solubility enhancements of pure solids have been evaluated in terms of the interaction energy densities of the solute-co-solvent and solute-solvent specific interactions, which can, in turn, be predicted from the pure-component characteristic physical properties.

Solid solubilities in supercritical fluids from group contributions

Abstract Inclusion of a covolume dependent mixing rule for the energy parameter enables the prediction of solubility of solids in supercritical fluids. This approach avoids the use of difficult-to-obtain critical properties and acentric factors and involves simple characteristic properties, namely the van der Waals volume and the heat of sublimation of the solid. These properties are predicted using the molecular structure and the Bondis group contribution method. The predictions of solubilities by the proposed model, including those not employed in the development of the model, are found to be in good agreement with the experimental data on solubilities of a range of solids in supercritical carbon dioxide, ethane, and ethylene.

Effect of covolume dependency of the energy parameter on the predictability of SCFE data using the Peng-Robinson equation of state

Abstract Improved solubility data predictions by the Peng-Robinson equation-of-state (PR-EOS) for supercritical fluid-solid systems are obtained for asymmetric systems by employing the covolume dependency in the mixing rule for the attraction parameter, a , along with the corresponding states approach for both like and unlike pair parameters of the EOS. This method reduces the sensitivity of solubility predictions to variations in the value of the interaction parameter and allows the binary interaction parameter to be correlated in terms of the pure component properties with small sacrifice in accuracy. The solubility data predictions using the developed correlation for supercritical carbon dioxide and hydrocarbon solvents compare well with the experimental results.

Pressurised Hot Water as a Novel Extractant of Natural Products: A Review

Abstract Pressurised hot water extraction (PHWE) has emerged as a highly promising energy-efficient and environmentally benign technique for recovering bioactive molecules from natural materials using sub-critical compressed liquid water in the temperature range of 80-180°C. It is set to replace conventional solvent extraction, pressurised organic solvent extraction or supercritical fluid extraction (SCFE) to obviate their limitations. A critical review on variations in the characteristic properties of PHW and the factors influencing the performance of PHWE process reveals its great potential to improve the yield and quality, by proper optimisation of process parameters. This novel extractant can be utilised to efficiently obtain clean product from a variety of natural substances.

Modeling dilute supercritical mixtures utilizing solvent-cluster interactions

Abstract Supercritical fluids are, in general, known to dissolve solids and to result in dilute mixtures representing a class by themselves. The asymmetry between the large solute and small solvent molecules, and the strong solute-solvent interactions render a nonuniform, nonrandom distribution of solvent molecules. The present study proposes a model for the binary interactions in the dilute SC mixtures and demonstrates how an adequate representation of the attraction energy and size — parameters of the cluster accounts for both short-range and long-range interactions. The EOS parameters for the cluster are obtained by incorporating covolume dependency of the short-range interactions between the solvent and solute molecules constituting the cluster. This facilitates reduction in the difference in the energy and size parameters of the interacting species for long-range interactions. The behavior of the solvent population in the cluster conforms to the spectroscopically observed behavior of the clustering phenomena reported in the literature. The validity of the model is successfully verified by the predictions of partial molar volume data and the solubilities of binary mixtures of solids in SCF.

Purification of Phytochemicals by Gas Antisolvent Precipitation with Carbon Dioxide

Abstract Gas antisolvent precipitation (GAP) using dense carbon dioxide (CO2) is a novel technique for the purification or enrichment of phytochemicals by selective crystallisation. It involves dissolution of sub-critical CO2 into an organic solution of the extract for selectively reducing the solubility of the solid solutes of interest by anti-solvent effect. The recovery and enrichment of three bioactive phytochemicals, such as β-carotene, α-hydroxycitric acid, and licochalcone-A have been investigated in this paper. Initially, organic solvent (Soxhlet) extraction or supercritical CO2 extraction has been carried out for the recovery of β-carotene from mango leaves, α-hydroxycitric acid from kokum, and licochalcone-A from licorice. Subsequently, purification has been performed by the GAP process using CO2 in the pressure range of 40 to 70 bar at 298 K, followed by filtration at the same pressure and temperature, and removal of the residual solvent from the product by flushing it with CO2. High performance liquid chromatography (HPLC) analysis of the phytochemicals before and after the GAP process confirms significant enrichment of the active ingredients.

Recovery of Phytochemicals from Kokum (Garcinia indica choisy) Using Pressurized Hot Water

A novel process has been developed for the recovery of phytochemicals such as, ? -HCA from kokum (Garcinia indica choisy) rinds using hot water pressurized with carbon dioxide, followed by its purification. The performance of the pressurized hot water extraction (PHWE) process has been evaluated to ascertain the optimum process parameters for maximizing the recovery of ? -HCA. A systematic parametric study has been undertaken by varying the important parameters in the ranges of 30-120 °C for temperature, 1-20 atm for pressure, 30-60 min of extraction time, 4 - 22 ml/g of water to feed ratio, 1-3 number of stages , 0-350 rpm of stirring, presence of salt, nature of feed, and grinding. Ethanol is added to the aqueous extract from kokum rinds for the removal of pectinous materials by precipitation. Quantification of ? -HCA in the product has been carried out by the titration method with 0.1N NaOH solution. The maximum recovery is obtained when PHWE is carried out at 90 °C above which the recovery decreases. Pressure does not have much effect on the recovery of ? -HCA beyond a certain pressure required to maintain the extractant in the liquid phase. More ?-HCA is recovered by 2-stage PHWE from ground dry kokum than from salty kokum rinds.

Robust Silica Aerogel Microspheres from Rice Husk Ash to Enhance the Dissolution Rate of Poorly Water-Soluble Drugs

The present paper demonstrates the capability of specially prepared robust silica aerogel microspheres (RSAMs) to enhance the dissolution rate of poorly water-soluble drugs. A sol-gel/mineral oil emulsion method has been developed for RSAMs from rice husk ash (RHA), a biogenic source. The particles were characterized for their Brunauer–Emmett–Teller (BET) specific surface area, Barrett, Joyner and Halenda (BJH) pore volume and pore diameter, and morphology by optical microscopy and scanning electron microscopy (SEM). The dissolution rate of ibuprofen, a poorly water-soluble drug, was investigated by adsorbing it onto RSAMs upon dissolving it in supercritical carbon dioxide (scCO2) at 150 bar and 40°C. This resulted in a loading of ∼0.13 g ibuprofen/g loaded RSAMs in 24 h. X-ray diffraction analysis was used to characterize the nature of the adsorbed ibuprofen onto RSAMs. It was observed that the loaded drug on the aerogels is in amorphous form. An in vitro drug-release kinetic studies confirmed a significant enhancement in the dissolution rate, namely ∼100% of the loaded ibuprofen released as compared to that of ∼11% of crystalline ibuprofen in 15 min.