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Papers by Masood Valavi

Journal of Pharmaceutical Sciences, 2014

The antifungal drug, 5-fluorocytosine (FC), is marketed as a capsule (250 or 500 mg strength) ins... more The antifungal drug, 5-fluorocytosine (FC), is marketed as a capsule (250 or 500 mg strength) instead of the preferred tablet dosage form. Through systematic characterization of solid-state properties, including mechanical properties, we identify tabletability and poor physical stability of FC as the problems that likely have prevented the successful development of a FC tablet product. We then design an FC oxalate 2:1 salt (FCOXA21), based on established relationship between crystal structure and properties, to address these deficient properties. FCOXA21 is subsequently used to develop a direct compression tablet product using predictive and material-sparing powder characterization tools, that is, ring shear cell for powder flowability and compaction simulator for powder tabletability. The initial tablet formulation, which contains 84.5% (wt %) FCOXA21, exhibits excellent tabletability but inadequate flowability. We solve the powder flowability problem through controlling the particle size of FCOXA21. A batch of FCOXA21 tablets (500 mg FC equivalent dose) is then prepared. Finally, systematic evaluation on tablet weight variation, content uniformity, friability, and dissolution using standard methods confirms the commercial manufacturability of FC tablets. Through this work, we have demonstrated the potential of integrated crystal and particle engineering in expediting the development of tablet products of challenging drugs using the economical direct compression process.

Advanced engineering materials, Jun 17, 2024

peer-reviewedThis study investigated two important thermodynamic parameters of crystallisation: t... more peer-reviewedThis study investigated two important thermodynamic parameters of crystallisation: the activity coefficient and solubility. The influence of composition and temperature on the activity coefficient was investigated to provide a better approximation of the driving force of crystallisation. It was found that the influence of temperature on the activity coefficient was generally much smaller than the influence of composition. Based on an analysis that was performed, a new estimation of the driving force was suggested. Since the driving force is also dependent on solubility, it is important to have an accurate estimation of solubility. Three models were used to calculate a solubility curve: “original NRTL-SAC”, “temperature-dependent NRTL-SAC” and “Pharma UNIFAC”. A comparison between the performances of these three models was presented. It was found that introducing a temperature-dependent binary interaction parameter to the original NRTL-SAC model could improve this model’...

Journal of Pharmaceutical Sciences, Jun 1, 2016

Melting temperatures and enthalpies of fusion have been determined by differential scanning calor... more Melting temperatures and enthalpies of fusion have been determined by differential scanning calorimetry (DSC) for two polymorphs of the drug tolbutamide: FI H and FV. Heat capacities have been determined by temperature-modulated DSC for four polymorphs: FI L , FI H , FII, FV, and for the supercooled melt. The enthalpy of fusion of FII at its melting point has been estimated from the enthalpy of transition of FII into FI H through a thermodynamic cycle. Calorimetric data has been used to derive a quantitative polymorphic stability relationship between these four polymorphs, showing that FII is the stable polymorph below approx. 333 K, above which temperature FI H is the stable form up to its melting point. The relative stability of FV is well below the other polymorphs. The previously reported kinetic reversibility of the transformation between FI L and FI H has been verified using in situ Raman spectroscopy. The solid-liquid solubility of FII has been gravimetrically determined in five pure organic solvents (methanol, 1-propanol, ethyl acetate, acetonitrile and toluene) over the temperature range 278 K-323 K. The ideal solubility has been estimated from calorimetric data, and solution activity coefficients at saturation in the five solvents determined. All solutions show positive deviation from Raoult's law, and all van't Hoff plots of solubility data are non-linear. The solubility in toluene is well below that observed in the other investigated solvents. Solubility data has been correlated and extrapolated to the melting point using a semiempirical regression model.

Journal of Pharmaceutical Sciences, Jul 1, 2019

The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-prop... more The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-propanol, 1-butanol, and toluene over the temperature range 268-298 K. Polymorph transition and melting temperatures, associated enthalpy changes, and the heat capacity of the solid forms and the supercooled melt have been measured by differential scanning calorimetry. Based on extrapolated calorimetric data, the Gibbs energy, enthalpy and entropy of fusion, and the activity of solid butamben (the ideal solubility) have been calculated from below ambient temperature up to the melting point. Activity coefficients of butamben at equilibrium in the different solvents have been estimated from solubility data and the activity of the solid, revealing that all investigated systems exhibit positive deviation from Raoult's law. Solubility data are well correlated by a semiempirical regression model. On a mass basis, the solubility is clearly higher in methanol than in the other solvents, but mole fraction solubilities are very similar across all 5 solvents. The 2 known polymorphs are enantiotropically related, and the transition point is located at 283 K. Polymorph interconversions occur within 0.3 K of the transition point even in the solid state, and the 2 forms exhibit strong similarities in investigated properties.

Industrial & Engineering Chemistry Research, Oct 12, 2016

In this work, the NRTL-SAC and the Pharma UNIFAC models are evaluated with respect to the capabil... more In this work, the NRTL-SAC and the Pharma UNIFAC models are evaluated with respect to the capability of prediction of solid-liquid equilibria of pharmaceutical compounds in organic solvents. The original NRTL-SAC model is extended through the introduction of temperaturedependent binary interaction parameters, and the two versions of the model are parametrized using VLE data. The performance of the NRTL-SAC models for correlation and prediction of the 2 solubility of eight medium-sized flexible pharmaceutical or pharmaceutically similar molecules in multiple pure, organic solvents is examined: risperidone, fenofibrate, fenoxycarb, tolbutamide, meglumine, butyl paraben, butamben and salicylamide. The performance of the Pharma UNIFAC model is evaluated using data for six of these compounds. In general, it is found that introducing a dependence on temperature to the binary interaction parameters of the NRTL-SAC model can improve its capability for modeling and prediction of the solubility of active pharmaceutical ingredients. For prediction of solubility data the Pharma UNIFAC model generally performs below the two NRTL-SAC models. Averaged over all evaluated systems where the solubility was predicted with each method, the root mean squared logarithmic error in predicted mole fraction solubility obtained for Pharma UNIFAC (30 systems) and for the original and the modified temperature-dependent forms of the NRTL-SAC model (29 systems) are 1.64, 1.17 and 1.09, respectively. Comparing only those systems for which all models were evaluated (18 systems), the RMSLE values are 1.42, 1.06 and 0.87, respectively.

Journal of Solution Chemistry, Aug 1, 2013

ABSTRACT In this study, the perturbed hard sphere chain equation of state is utilized to calculat... more ABSTRACT In this study, the perturbed hard sphere chain equation of state is utilized to calculate the activity of water in binary and ternary solutions of polyethylene glycol (PEG), salt and water. The liquid density of the binary and ternary solutions is also predicted. To estimate the water activity in PEG–water binary systems, a linear correlation is obtained for the binary interaction parameter between water and PEG. Then, using this correlation and without introducing any additional binary parameters, the water activities are predicted in ternary solutions of water, salt and PEG with different molecular weights (MW). Our results show that the mean absolute average relative deviation (AARD %) of water activity for binary PEG–water solutions in 298 K is 0.73 %. In addition, the water activity in ternary solutions of water and two PEGs with different MW is predicted within 0.31 % AARD %. Furthermore, the AARD % for prediction of water activities in binary PEG–water solutions over the temperature range 308–338 K is 0.41 %. Also, the water activities of aqueous two-phase systems are predicted with AARD % = 0.64 %. In this regard, no adjustable parameters were correlated between salt and PEG. Finally, liquid densities were predicted in binary solutions of water–PEG and ternary solutions of water–PEG–salt.

Fluid Phase Equilibria, Nov 1, 2012

In this work the modified perturbed hard sphere chain equation of state (PHSC), coupled with Van ... more In this work the modified perturbed hard sphere chain equation of state (PHSC), coupled with Van der waals Platteuw model, has been used for prediction of gas hydrate formation (dissociation) conditions. The PHSC EOS has been modified using association and electrostatic contributions. In order to evaluate the capability of the PHSC EOS, the hydrate formation conditions of various pure as well as mixed gases in the presence and absence of the thermodynamic inhibitors such as methanol, ethanol, mono ethylene glycol(MEG), NaCl, KCl and CaCl 2 have been studied. In the absence of inhibitors, the pure gas hydrate formation conditions have been predicted within 3.4% absolute average relative deviation. The hydrate formation condition of gas mixtures have been predicted within AARD 4.6%. In the presence of organic inhibitors and single electrolyte 6.1% and 5.8% AARD has been observed respectively. A total of 102 systems have been studied; our results showed that the PHSC EOS is capable of prediction of hydrate formation condition with reasonable absolute average relative deviation (AARD) from experimental data.

Journal of Molecular Liquids, Nov 1, 2014

ABSTRACT The Perturbed Hard Sphere Chain (PHSC) equation of state (EoS) has been utilized for the... more ABSTRACT The Perturbed Hard Sphere Chain (PHSC) equation of state (EoS) has been utilized for thermodynamic modeling of aqueous amino acid and peptide solutions. For this purpose, the parameters of amino acids and peptides have been adjusted to activity coefficient, liquid density and solubility of amino acids and peptides in water. Furthermore, water activity, osmotic coefficient and vapor pressure of aqueous amino acid solution have been predicted. Finally the solubility of amino acid mixtures in water has been calculated using additional adjustable parameters. The results of PHSC EoS were in good agreement with experimental data. Average deviations in estimation of activity coefficients, liquid densities, water activity and osmotic coefficient are 1.44%, 0.38%, 0.067% and 2.6%, respectively. In addition the solubility of mixed aqueous amino acids has been calculated to show the ability of mentioned model.

Journal of Molecular Liquids, Nov 1, 2017

In this work, solubility of four Active Pharmaceutical Ingredients (APIs) including Butyl Paraben... more In this work, solubility of four Active Pharmaceutical Ingredients (APIs) including Butyl Paraben, Fenoxycarb, Fenofibrate and Risperidone were predicted using Hansen Flory Huggins model using two different scenarios. In the first method, activity coefficient of APIs were obtained through fitting the experimental activity coefficients of solvents at particular temperature of 293 K, then components solubility in entire temperature range of study was predicted. In the second scenario, the model parameters were adjusted using experimental data of two selected solvents, then components solubility were predicted in other solvents. In order to check the physical meanings of obtained values, Molecular Dynamic (MD) simulations was utilized and the results were compared. Finally the predictive capabilities of two Hansen Flory Huggins models were compared to temperature-dependent NRTL-SAC model.

Journal of Pharmaceutical Sciences, 2019

The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-prop... more The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-propanol, 1-butanol, and toluene over the temperature range 268-298 K. Polymorph transition and melting temperatures, associated enthalpy changes, and the heat capacity of the solid forms and the supercooled melt have been measured by differential scanning calorimetry. Based on extrapolated calorimetric data, the Gibbs energy, enthalpy and entropy of fusion, and the activity of solid butamben (the ideal solubility) have been calculated from below ambient temperature up to the melting point. Activity coefficients of butamben at equilibrium in the different solvents have been estimated from solubility data and the activity of the solid, revealing that all investigated systems exhibit positive deviation from Raoult's law. Solubility data are well correlated by a semiempirical regression model. On a mass basis, the solubility is clearly higher in methanol than in the other solvents, but mole fraction solubilities are very similar across all 5 solvents. The 2 known polymorphs are enantiotropically related, and the transition point is located at 283 K. Polymorph interconversions occur within 0.3 K of the transition point even in the solid state, and the 2 forms exhibit strong similarities in investigated properties.

Industrial & Engineering Chemistry Research, 2016

In this work, the NRTL-SAC and the Pharma UNIFAC models are evaluated with respect to the capabil... more In this work, the NRTL-SAC and the Pharma UNIFAC models are evaluated with respect to the capability of prediction of solid-liquid equilibria of pharmaceutical compounds in organic solvents. The original NRTL-SAC model is extended through the introduction of temperaturedependent binary interaction parameters, and the two versions of the model are parametrized using VLE data. The performance of the NRTL-SAC models for correlation and prediction of the solubility of eight medium-sized flexible pharmaceutical or pharmaceutically similar molecules in multiple pure, organic solvents is examined: risperidone, fenofibrate, fenoxycarb, tolbutamide, meglumine, butyl paraben, butamben and salicylamide. The performance of the Pharma UNIFAC model is evaluated using data for six of these compounds. In general, it is found that introducing a dependence on temperature to the binary interaction parameters of the NRTL-SAC model can improve its capability for modeling and prediction of the solubility of active pharmaceutical ingredients. For prediction of solubility data the Pharma UNIFAC model generally performs below the two NRTL-SAC models. Averaged over all evaluated systems where the solubility was predicted with each method, the root mean squared logarithmic error in predicted mole fraction solubility obtained for Pharma UNIFAC (30 systems) and for the original and the modified temperature-dependent forms of the NRTL-SAC model (29 systems) are 1.64, 1.17 and 1.09, respectively. Comparing only those systems for which all models were evaluated (18 systems), the RMSLE values are 1.42, 1.06 and 0.87, respectively.

Crystal Growth & Design, 2016

In this work the influence of temperature and composition on the activity coefficient in solution... more In this work the influence of temperature and composition on the activity coefficient in solution has been investigated, based on isothermal and isobaric vapor-liquid equilibrium data for 30 binary systems classified into four groups: water-organic, polar-polar, polar-nonpolar and nonpolarnonpolar systems. It is shown that under most conditions the temperature-dependence of the activity coefficient is clearly weaker than the composition-dependence. The analysis is extended to include solid-liquid solubility data of 15 binary systems of relatively large and complex organic molecules in organic solvents. Based on this, a novel approach to estimate the thermodynamic driving force of crystallization from solution is proposed. Rather than assuming that the activity coefficient ratio equals unity, it is shown that in most cases a more accurate assumption is to neglect only the temperature-dependence of the activity coefficient. This allows the activity coefficient ratio to be estimated from solid-liquid equilibrium data.

Journal of Pharmaceutical Sciences, 2016

Melting temperatures and enthalpies of fusion have been determined by differential scanning calor... more Melting temperatures and enthalpies of fusion have been determined by differential scanning calorimetry (DSC) for two polymorphs of the drug tolbutamide: FI H and FV. Heat capacities have been determined by temperature-modulated DSC for four polymorphs: FI L , FI H , FII, FV, and for the supercooled melt. The enthalpy of fusion of FII at its melting point has been estimated from the enthalpy of transition of FII into FI H through a thermodynamic cycle. Calorimetric data has been used to derive a quantitative polymorphic stability relationship between these four polymorphs, showing that FII is the stable polymorph below approx. 333 K, above which temperature FI H is the stable form up to its melting point. The relative stability of FV is well below the other polymorphs. The previously reported kinetic reversibility of the transformation between FI L and FI H has been verified using in situ Raman spectroscopy. The solid-liquid solubility of FII has been gravimetrically determined in five pure organic solvents (methanol, 1-propanol, ethyl acetate, acetonitrile and toluene) over the temperature range 278 K-323 K. The ideal solubility has been estimated from calorimetric data, and solution activity coefficients at saturation in the five solvents determined. All solutions show positive deviation from Raoult's law, and all van't Hoff plots of solubility data are non-linear. The solubility in toluene is well below that observed in the other investigated solvents. Solubility data has been correlated and extrapolated to the melting point using a semiempirical regression model.

Journal of Molecular Liquids, 2014

ABSTRACT The Perturbed Hard Sphere Chain (PHSC) equation of state (EoS) has been utilized for the... more ABSTRACT The Perturbed Hard Sphere Chain (PHSC) equation of state (EoS) has been utilized for thermodynamic modeling of aqueous amino acid and peptide solutions. For this purpose, the parameters of amino acids and peptides have been adjusted to activity coefficient, liquid density and solubility of amino acids and peptides in water. Furthermore, water activity, osmotic coefficient and vapor pressure of aqueous amino acid solution have been predicted. Finally the solubility of amino acid mixtures in water has been calculated using additional adjustable parameters. The results of PHSC EoS were in good agreement with experimental data. Average deviations in estimation of activity coefficients, liquid densities, water activity and osmotic coefficient are 1.44%, 0.38%, 0.067% and 2.6%, respectively. In addition the solubility of mixed aqueous amino acids has been calculated to show the ability of mentioned model.

Journal of Solution Chemistry, 2013

ABSTRACT In this study, the perturbed hard sphere chain equation of state is utilized to calculat... more ABSTRACT In this study, the perturbed hard sphere chain equation of state is utilized to calculate the activity of water in binary and ternary solutions of polyethylene glycol (PEG), salt and water. The liquid density of the binary and ternary solutions is also predicted. To estimate the water activity in PEG–water binary systems, a linear correlation is obtained for the binary interaction parameter between water and PEG. Then, using this correlation and without introducing any additional binary parameters, the water activities are predicted in ternary solutions of water, salt and PEG with different molecular weights (MW). Our results show that the mean absolute average relative deviation (AARD %) of water activity for binary PEG–water solutions in 298 K is 0.73 %. In addition, the water activity in ternary solutions of water and two PEGs with different MW is predicted within 0.31 % AARD %. Furthermore, the AARD % for prediction of water activities in binary PEG–water solutions over the temperature range 308–338 K is 0.41 %. Also, the water activities of aqueous two-phase systems are predicted with AARD % = 0.64 %. In this regard, no adjustable parameters were correlated between salt and PEG. Finally, liquid densities were predicted in binary solutions of water–PEG and ternary solutions of water–PEG–salt.

Fluid Phase Equilibria, 2013

In this work, the capability of the Perturbed Hard Sphere Chain (PHSC) equation of state (EOS) in... more In this work, the capability of the Perturbed Hard Sphere Chain (PHSC) equation of state (EOS) in liquid-liquid equilibrium calculations of salt-polyethylene glycol (PEG)-water systems is investigated. In order to present a comprehensive model, association as well as electrostatic contributions have been added to the original PHSC EOS. In this work 47 systems including PEG (with different molecular weights) and various salts have been modeled at different temperatures. Only two adjustable parameters between salt and PEG and between water and PEG have been employed. Good agreement between experimental data and calculation results is observed. Overall average deviation for all of the systems considered is 6.81%. This study shows that the PHSC EOS can be employed for correlation of phase behavior in aqueous two phase systems.

Journal of Pharmaceutical Sciences, 2014

The antifungal drug, 5-fluorocytosine (FC), is marketed as a capsule (250 or 500 mg strength) ins... more The antifungal drug, 5-fluorocytosine (FC), is marketed as a capsule (250 or 500 mg strength) instead of the preferred tablet dosage form. Through systematic characterization of solid-state properties, including mechanical properties, we identify tabletability and poor physical stability of FC as the problems that likely have prevented the successful development of a FC tablet product. We then design an FC oxalate 2:1 salt (FCOXA21), based on established relationship between crystal structure and properties, to address these deficient properties. FCOXA21 is subsequently used to develop a direct compression tablet product using predictive and material-sparing powder characterization tools, that is, ring shear cell for powder flowability and compaction simulator for powder tabletability. The initial tablet formulation, which contains 84.5% (wt %) FCOXA21, exhibits excellent tabletability but inadequate flowability. We solve the powder flowability problem through controlling the particle size of FCOXA21. A batch of FCOXA21 tablets (500 mg FC equivalent dose) is then prepared. Finally, systematic evaluation on tablet weight variation, content uniformity, friability, and dissolution using standard methods confirms the commercial manufacturability of FC tablets. Through this work, we have demonstrated the potential of integrated crystal and particle engineering in expediting the development of tablet products of challenging drugs using the economical direct compression process.

Advanced engineering materials, Jun 17, 2024

peer-reviewedThis study investigated two important thermodynamic parameters of crystallisation: t... more peer-reviewedThis study investigated two important thermodynamic parameters of crystallisation: the activity coefficient and solubility. The influence of composition and temperature on the activity coefficient was investigated to provide a better approximation of the driving force of crystallisation. It was found that the influence of temperature on the activity coefficient was generally much smaller than the influence of composition. Based on an analysis that was performed, a new estimation of the driving force was suggested. Since the driving force is also dependent on solubility, it is important to have an accurate estimation of solubility. Three models were used to calculate a solubility curve: “original NRTL-SAC”, “temperature-dependent NRTL-SAC” and “Pharma UNIFAC”. A comparison between the performances of these three models was presented. It was found that introducing a temperature-dependent binary interaction parameter to the original NRTL-SAC model could improve this model’...

Journal of Pharmaceutical Sciences, Jun 1, 2016

Melting temperatures and enthalpies of fusion have been determined by differential scanning calor... more Melting temperatures and enthalpies of fusion have been determined by differential scanning calorimetry (DSC) for two polymorphs of the drug tolbutamide: FI H and FV. Heat capacities have been determined by temperature-modulated DSC for four polymorphs: FI L , FI H , FII, FV, and for the supercooled melt. The enthalpy of fusion of FII at its melting point has been estimated from the enthalpy of transition of FII into FI H through a thermodynamic cycle. Calorimetric data has been used to derive a quantitative polymorphic stability relationship between these four polymorphs, showing that FII is the stable polymorph below approx. 333 K, above which temperature FI H is the stable form up to its melting point. The relative stability of FV is well below the other polymorphs. The previously reported kinetic reversibility of the transformation between FI L and FI H has been verified using in situ Raman spectroscopy. The solid-liquid solubility of FII has been gravimetrically determined in five pure organic solvents (methanol, 1-propanol, ethyl acetate, acetonitrile and toluene) over the temperature range 278 K-323 K. The ideal solubility has been estimated from calorimetric data, and solution activity coefficients at saturation in the five solvents determined. All solutions show positive deviation from Raoult's law, and all van't Hoff plots of solubility data are non-linear. The solubility in toluene is well below that observed in the other investigated solvents. Solubility data has been correlated and extrapolated to the melting point using a semiempirical regression model.

Journal of Pharmaceutical Sciences, Jul 1, 2019

The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-prop... more The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-propanol, 1-butanol, and toluene over the temperature range 268-298 K. Polymorph transition and melting temperatures, associated enthalpy changes, and the heat capacity of the solid forms and the supercooled melt have been measured by differential scanning calorimetry. Based on extrapolated calorimetric data, the Gibbs energy, enthalpy and entropy of fusion, and the activity of solid butamben (the ideal solubility) have been calculated from below ambient temperature up to the melting point. Activity coefficients of butamben at equilibrium in the different solvents have been estimated from solubility data and the activity of the solid, revealing that all investigated systems exhibit positive deviation from Raoult's law. Solubility data are well correlated by a semiempirical regression model. On a mass basis, the solubility is clearly higher in methanol than in the other solvents, but mole fraction solubilities are very similar across all 5 solvents. The 2 known polymorphs are enantiotropically related, and the transition point is located at 283 K. Polymorph interconversions occur within 0.3 K of the transition point even in the solid state, and the 2 forms exhibit strong similarities in investigated properties.

Industrial & Engineering Chemistry Research, Oct 12, 2016

In this work, the NRTL-SAC and the Pharma UNIFAC models are evaluated with respect to the capabil... more In this work, the NRTL-SAC and the Pharma UNIFAC models are evaluated with respect to the capability of prediction of solid-liquid equilibria of pharmaceutical compounds in organic solvents. The original NRTL-SAC model is extended through the introduction of temperaturedependent binary interaction parameters, and the two versions of the model are parametrized using VLE data. The performance of the NRTL-SAC models for correlation and prediction of the 2 solubility of eight medium-sized flexible pharmaceutical or pharmaceutically similar molecules in multiple pure, organic solvents is examined: risperidone, fenofibrate, fenoxycarb, tolbutamide, meglumine, butyl paraben, butamben and salicylamide. The performance of the Pharma UNIFAC model is evaluated using data for six of these compounds. In general, it is found that introducing a dependence on temperature to the binary interaction parameters of the NRTL-SAC model can improve its capability for modeling and prediction of the solubility of active pharmaceutical ingredients. For prediction of solubility data the Pharma UNIFAC model generally performs below the two NRTL-SAC models. Averaged over all evaluated systems where the solubility was predicted with each method, the root mean squared logarithmic error in predicted mole fraction solubility obtained for Pharma UNIFAC (30 systems) and for the original and the modified temperature-dependent forms of the NRTL-SAC model (29 systems) are 1.64, 1.17 and 1.09, respectively. Comparing only those systems for which all models were evaluated (18 systems), the RMSLE values are 1.42, 1.06 and 0.87, respectively.

Journal of Solution Chemistry, Aug 1, 2013

ABSTRACT In this study, the perturbed hard sphere chain equation of state is utilized to calculat... more ABSTRACT In this study, the perturbed hard sphere chain equation of state is utilized to calculate the activity of water in binary and ternary solutions of polyethylene glycol (PEG), salt and water. The liquid density of the binary and ternary solutions is also predicted. To estimate the water activity in PEG–water binary systems, a linear correlation is obtained for the binary interaction parameter between water and PEG. Then, using this correlation and without introducing any additional binary parameters, the water activities are predicted in ternary solutions of water, salt and PEG with different molecular weights (MW). Our results show that the mean absolute average relative deviation (AARD %) of water activity for binary PEG–water solutions in 298 K is 0.73 %. In addition, the water activity in ternary solutions of water and two PEGs with different MW is predicted within 0.31 % AARD %. Furthermore, the AARD % for prediction of water activities in binary PEG–water solutions over the temperature range 308–338 K is 0.41 %. Also, the water activities of aqueous two-phase systems are predicted with AARD % = 0.64 %. In this regard, no adjustable parameters were correlated between salt and PEG. Finally, liquid densities were predicted in binary solutions of water–PEG and ternary solutions of water–PEG–salt.

Fluid Phase Equilibria, Nov 1, 2012

In this work the modified perturbed hard sphere chain equation of state (PHSC), coupled with Van ... more In this work the modified perturbed hard sphere chain equation of state (PHSC), coupled with Van der waals Platteuw model, has been used for prediction of gas hydrate formation (dissociation) conditions. The PHSC EOS has been modified using association and electrostatic contributions. In order to evaluate the capability of the PHSC EOS, the hydrate formation conditions of various pure as well as mixed gases in the presence and absence of the thermodynamic inhibitors such as methanol, ethanol, mono ethylene glycol(MEG), NaCl, KCl and CaCl 2 have been studied. In the absence of inhibitors, the pure gas hydrate formation conditions have been predicted within 3.4% absolute average relative deviation. The hydrate formation condition of gas mixtures have been predicted within AARD 4.6%. In the presence of organic inhibitors and single electrolyte 6.1% and 5.8% AARD has been observed respectively. A total of 102 systems have been studied; our results showed that the PHSC EOS is capable of prediction of hydrate formation condition with reasonable absolute average relative deviation (AARD) from experimental data.

Journal of Molecular Liquids, Nov 1, 2014

ABSTRACT The Perturbed Hard Sphere Chain (PHSC) equation of state (EoS) has been utilized for the... more ABSTRACT The Perturbed Hard Sphere Chain (PHSC) equation of state (EoS) has been utilized for thermodynamic modeling of aqueous amino acid and peptide solutions. For this purpose, the parameters of amino acids and peptides have been adjusted to activity coefficient, liquid density and solubility of amino acids and peptides in water. Furthermore, water activity, osmotic coefficient and vapor pressure of aqueous amino acid solution have been predicted. Finally the solubility of amino acid mixtures in water has been calculated using additional adjustable parameters. The results of PHSC EoS were in good agreement with experimental data. Average deviations in estimation of activity coefficients, liquid densities, water activity and osmotic coefficient are 1.44%, 0.38%, 0.067% and 2.6%, respectively. In addition the solubility of mixed aqueous amino acids has been calculated to show the ability of mentioned model.

Journal of Molecular Liquids, Nov 1, 2017

In this work, solubility of four Active Pharmaceutical Ingredients (APIs) including Butyl Paraben... more In this work, solubility of four Active Pharmaceutical Ingredients (APIs) including Butyl Paraben, Fenoxycarb, Fenofibrate and Risperidone were predicted using Hansen Flory Huggins model using two different scenarios. In the first method, activity coefficient of APIs were obtained through fitting the experimental activity coefficients of solvents at particular temperature of 293 K, then components solubility in entire temperature range of study was predicted. In the second scenario, the model parameters were adjusted using experimental data of two selected solvents, then components solubility were predicted in other solvents. In order to check the physical meanings of obtained values, Molecular Dynamic (MD) simulations was utilized and the results were compared. Finally the predictive capabilities of two Hansen Flory Huggins models were compared to temperature-dependent NRTL-SAC model.

Journal of Pharmaceutical Sciences, 2019

The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-prop... more The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-propanol, 1-butanol, and toluene over the temperature range 268-298 K. Polymorph transition and melting temperatures, associated enthalpy changes, and the heat capacity of the solid forms and the supercooled melt have been measured by differential scanning calorimetry. Based on extrapolated calorimetric data, the Gibbs energy, enthalpy and entropy of fusion, and the activity of solid butamben (the ideal solubility) have been calculated from below ambient temperature up to the melting point. Activity coefficients of butamben at equilibrium in the different solvents have been estimated from solubility data and the activity of the solid, revealing that all investigated systems exhibit positive deviation from Raoult's law. Solubility data are well correlated by a semiempirical regression model. On a mass basis, the solubility is clearly higher in methanol than in the other solvents, but mole fraction solubilities are very similar across all 5 solvents. The 2 known polymorphs are enantiotropically related, and the transition point is located at 283 K. Polymorph interconversions occur within 0.3 K of the transition point even in the solid state, and the 2 forms exhibit strong similarities in investigated properties.

Industrial & Engineering Chemistry Research, 2016

In this work, the NRTL-SAC and the Pharma UNIFAC models are evaluated with respect to the capabil... more In this work, the NRTL-SAC and the Pharma UNIFAC models are evaluated with respect to the capability of prediction of solid-liquid equilibria of pharmaceutical compounds in organic solvents. The original NRTL-SAC model is extended through the introduction of temperaturedependent binary interaction parameters, and the two versions of the model are parametrized using VLE data. The performance of the NRTL-SAC models for correlation and prediction of the solubility of eight medium-sized flexible pharmaceutical or pharmaceutically similar molecules in multiple pure, organic solvents is examined: risperidone, fenofibrate, fenoxycarb, tolbutamide, meglumine, butyl paraben, butamben and salicylamide. The performance of the Pharma UNIFAC model is evaluated using data for six of these compounds. In general, it is found that introducing a dependence on temperature to the binary interaction parameters of the NRTL-SAC model can improve its capability for modeling and prediction of the solubility of active pharmaceutical ingredients. For prediction of solubility data the Pharma UNIFAC model generally performs below the two NRTL-SAC models. Averaged over all evaluated systems where the solubility was predicted with each method, the root mean squared logarithmic error in predicted mole fraction solubility obtained for Pharma UNIFAC (30 systems) and for the original and the modified temperature-dependent forms of the NRTL-SAC model (29 systems) are 1.64, 1.17 and 1.09, respectively. Comparing only those systems for which all models were evaluated (18 systems), the RMSLE values are 1.42, 1.06 and 0.87, respectively.

Crystal Growth & Design, 2016

In this work the influence of temperature and composition on the activity coefficient in solution... more In this work the influence of temperature and composition on the activity coefficient in solution has been investigated, based on isothermal and isobaric vapor-liquid equilibrium data for 30 binary systems classified into four groups: water-organic, polar-polar, polar-nonpolar and nonpolarnonpolar systems. It is shown that under most conditions the temperature-dependence of the activity coefficient is clearly weaker than the composition-dependence. The analysis is extended to include solid-liquid solubility data of 15 binary systems of relatively large and complex organic molecules in organic solvents. Based on this, a novel approach to estimate the thermodynamic driving force of crystallization from solution is proposed. Rather than assuming that the activity coefficient ratio equals unity, it is shown that in most cases a more accurate assumption is to neglect only the temperature-dependence of the activity coefficient. This allows the activity coefficient ratio to be estimated from solid-liquid equilibrium data.

Journal of Pharmaceutical Sciences, 2016

Melting temperatures and enthalpies of fusion have been determined by differential scanning calor... more Melting temperatures and enthalpies of fusion have been determined by differential scanning calorimetry (DSC) for two polymorphs of the drug tolbutamide: FI H and FV. Heat capacities have been determined by temperature-modulated DSC for four polymorphs: FI L , FI H , FII, FV, and for the supercooled melt. The enthalpy of fusion of FII at its melting point has been estimated from the enthalpy of transition of FII into FI H through a thermodynamic cycle. Calorimetric data has been used to derive a quantitative polymorphic stability relationship between these four polymorphs, showing that FII is the stable polymorph below approx. 333 K, above which temperature FI H is the stable form up to its melting point. The relative stability of FV is well below the other polymorphs. The previously reported kinetic reversibility of the transformation between FI L and FI H has been verified using in situ Raman spectroscopy. The solid-liquid solubility of FII has been gravimetrically determined in five pure organic solvents (methanol, 1-propanol, ethyl acetate, acetonitrile and toluene) over the temperature range 278 K-323 K. The ideal solubility has been estimated from calorimetric data, and solution activity coefficients at saturation in the five solvents determined. All solutions show positive deviation from Raoult's law, and all van't Hoff plots of solubility data are non-linear. The solubility in toluene is well below that observed in the other investigated solvents. Solubility data has been correlated and extrapolated to the melting point using a semiempirical regression model.

Journal of Molecular Liquids, 2014

ABSTRACT The Perturbed Hard Sphere Chain (PHSC) equation of state (EoS) has been utilized for the... more ABSTRACT The Perturbed Hard Sphere Chain (PHSC) equation of state (EoS) has been utilized for thermodynamic modeling of aqueous amino acid and peptide solutions. For this purpose, the parameters of amino acids and peptides have been adjusted to activity coefficient, liquid density and solubility of amino acids and peptides in water. Furthermore, water activity, osmotic coefficient and vapor pressure of aqueous amino acid solution have been predicted. Finally the solubility of amino acid mixtures in water has been calculated using additional adjustable parameters. The results of PHSC EoS were in good agreement with experimental data. Average deviations in estimation of activity coefficients, liquid densities, water activity and osmotic coefficient are 1.44%, 0.38%, 0.067% and 2.6%, respectively. In addition the solubility of mixed aqueous amino acids has been calculated to show the ability of mentioned model.

Journal of Solution Chemistry, 2013

ABSTRACT In this study, the perturbed hard sphere chain equation of state is utilized to calculat... more ABSTRACT In this study, the perturbed hard sphere chain equation of state is utilized to calculate the activity of water in binary and ternary solutions of polyethylene glycol (PEG), salt and water. The liquid density of the binary and ternary solutions is also predicted. To estimate the water activity in PEG–water binary systems, a linear correlation is obtained for the binary interaction parameter between water and PEG. Then, using this correlation and without introducing any additional binary parameters, the water activities are predicted in ternary solutions of water, salt and PEG with different molecular weights (MW). Our results show that the mean absolute average relative deviation (AARD %) of water activity for binary PEG–water solutions in 298 K is 0.73 %. In addition, the water activity in ternary solutions of water and two PEGs with different MW is predicted within 0.31 % AARD %. Furthermore, the AARD % for prediction of water activities in binary PEG–water solutions over the temperature range 308–338 K is 0.41 %. Also, the water activities of aqueous two-phase systems are predicted with AARD % = 0.64 %. In this regard, no adjustable parameters were correlated between salt and PEG. Finally, liquid densities were predicted in binary solutions of water–PEG and ternary solutions of water–PEG–salt.

Fluid Phase Equilibria, 2013

In this work, the capability of the Perturbed Hard Sphere Chain (PHSC) equation of state (EOS) in... more In this work, the capability of the Perturbed Hard Sphere Chain (PHSC) equation of state (EOS) in liquid-liquid equilibrium calculations of salt-polyethylene glycol (PEG)-water systems is investigated. In order to present a comprehensive model, association as well as electrostatic contributions have been added to the original PHSC EOS. In this work 47 systems including PEG (with different molecular weights) and various salts have been modeled at different temperatures. Only two adjustable parameters between salt and PEG and between water and PEG have been employed. Good agreement between experimental data and calculation results is observed. Overall average deviation for all of the systems considered is 6.81%. This study shows that the PHSC EOS can be employed for correlation of phase behavior in aqueous two phase systems.