Apparent Thermodynamic Analysis Research Articles

Experimental analysis and modeling of aprepitant (an antiemetic drug for chemotherapy) solubility in subcritical water with/without co-solvent

This action described the experimental equilibrium solubility of aprepitant (APT), an antiemetic drug for chemotherapy, in subcritical water (SW) with/without ethanol as co-solvent, acquired through a static method between 298.15 and 393.15 K and 0–15 % (w/w) of ethanol and the constant pressure of 10 bar. The mole fraction of APT was obtained in the range of 0.39×10−4 to 9.10×10−4 while its mole fraction by cosolvent varied from 0.75×10−4 to 22.98×10−4. The obtained results represented the significant effect of solvent temperature on the solubility of APT. For both studied systems, the solubility data was successfully correlated with two well-known semi-empirical temperature-based models, namely the linear and modified Apelblat models. Results from applying statistical criteria exhibited that the modified Apelblat model had the highest accordance with experimental data. Finally, using the obtained correlation results, the apparent thermodynamic analysis including enthalpy, entropy, and Gibbs free energy of dissolution for APT dissolved in SW was obtained.

Interactions between components of choline chloride/propylene glycol or ethylene glycol deep eutectic solvents in the presence of water by determination of amlodipine besylate solubility profile

Improving amlodipine besylate (AMB) solubility as a poorly water-soluble drug is one of the biggest limits in preparation of different formulations in the pharmaceutical industry. Aiming to increase the aqueous AMB solubility, its solubility in choline chloride/propylene glycol (ChCl/PG) or choline chloride/ethylene glycol (ChCl/EG) deep eutectic solvents (DESs)-water mixtures was determined here using a shake-flask way at 293.2 K–313.2 K and ambient pressure (≈85 kPa) and correlated by models of van't Hoff, Jouyban-Acree and Jouyban-Acree-van't Hoff. In these mixtures, the maximum molarities of AMB (0.297 and 0.150 mol L−1) were determined at 313.15 K when the mass fraction of ChCl/PG and ChCl/EG were 0.8 and 1.0. The maximum AMB solubility in water was (0.008 mol L−1) at 313.15 K and observed an increment of 36.7-fold and 18.5-fold in ChCl/PG + water and ChCl/EG + water, respectively. The water effect on the stability of ChCl-PG or EG hydrogen bonding interactions was investigated by measuring the molarity of AMB in ternary mixtures of ChCl + PG or EG + water at 298.15 K. Comparing the obtained results for the above-mentioned binary and ternary mixtures presented that there is no real binary mixtures of DES and water when the water mass fraction was between 0.9 to 0.4 for ChCl/PG and 0.9 to 0.2 for ChCl/EG DESs, respectively. From correlation of AMB solubility with the selected cosolvency models, the mean percentage deviations were obtained between 3.4 % to 12.3 % which are on the acceptable range. Moreover, the consequences of apparent thermodynamic analysis demonstrated an endothermic and entropy-driven dissolution of AMB in all portions of ChCl/PG or ChCl/EG + water pseudo-binary mixtures.

The dissolution mechanism, molecular dynamics simulation and thermodynamic analysis of nirmatrelvir (treatment of COVID-19) in aqueous ethanol mixtures

This research investigates the cosolvent effect of nirmatrelvir (treatment of COVID-19) in ethanol + water mixtures. The result shows that the maximum solubility in mole fraction is 8.313 × 10−2 at the ethanol mass fraction of 80%, which is greater than that in pure water. The solvent effect analysis indicates that the hydrogen bond acidity (HBA) of solvent has the greatest impact on the solubility of nirmatrelvir solubility. The negative preferential solvation values in water-rich regions indicate that nirmatrelvir molecules are preferentially solvated by water molecules. With the rising mass fraction of cosolvent, ethanol disrupts the ordered structure of water molecules in solution through hydrogen bonding, allowing nirmatrelvir molecules to be preferentially solvated by ethanol. Nonetheless, nirmatrelvir molecules are preferentially solvated by water again in ethanol-rich regions. Through molecular dynamics calculations (MD), it could be found that the dissolution behavior is consistent with its calculated by solvation free energy calculation. Furthermore, the tall and sharp peak of the RDF plots of O···H-O (ethanol/water) and N-H···O (ethanol/water) were attained at 1.50–2.50 Å, indicating that ethanol and water molecules form a regular and definite coordination sphere around the nirmatrelvir moiety at the distance of 1.50–2.50 Å through hydrogen bonding form. Additionally, the correlation fitting was performed for the solubility data through the Jouyban-Acree model and its derivative models. Moreover, “Apparent thermodynamic analysis” of nirmatrelvir dissolution process in aqueous ethanol mixtures including entropy, enthalpy and Gibbs free energy were completed.

Solubility of ciprofloxacin in different solvents at several temperatures: Measurement, correlation, thermodynamics and Hansen solubility parameters

BackgroundCiprofloxacin is a commonly prescribed antibiotic drug whose solubility has not yet been completely studied. In this research, its equilibrium solubility at temperatures from T = (278.15 to 318.15) K in 13 neat solvents, namely, namely: 1,4-dioxane, polyethylene glycol (PEG) 600, PEG400, PEG300, N-methyl-2-pyrrolidone (NMP), PEG200, acetonitrile, N,N-dimethylformamide (DMF), ethanol, dimethyl sulfoxide (DMSO), methanol, ethylene glycol and water, is reported. MethodsFlask shake and UV–vis analysis were used for solubility determinations at different temperatures. Bottom solid phases were analyzed by DSC. Significant findingsMole fraction solubility of ciprofloxacin (x2) increases when temperature arises in all solvents. It varies from x2 = 4.11 · 10–6 in neat water to x2 = 1.55 · 10–3 in neat PEG200 at T = 298.15 K. Solubility behavior was adequately correlated by van't Hoff, van't Hoff-Yaws and Apelblat model. From the variation of solubility with temperature the apparent thermodynamic analysis of dissolution was performed in all the solvents. Total Hildebrand solubility parameter of ciprofloxacin (δ2) was calculated based on groups’ contributions by means of both the Fedors and the Hoftyzer-van Krevelen methods as δ2 = (26.4 and 25.7) MPa1/2, respectively. Otherwise, Hansen solubility parameters and total Hildebrand solubility parameter were also determined by using the Bustamante method from experimental solubility values in 16 neat solvents obtaining δ2 = 25.2 MPa1/2. Finally, KAT-LSER model was also employed to evaluate the role of different intermolecular interactions on the dissolution of ciprofloxacin.

Solubility of mesalazine in aqueous solutions of two betaine-based deep eutectic solvents at different temperatures: Data correlation and thermodynamic analysis

Temperature-dependent solubility data for mesalazine in the cosolvency systems composed of water and deep eutectic solvents (DESs) obtained from betaine as a hydrogen bond acceptor and ethylene glycol (EG) or propylene glycol (PG) as hydrogen bond donors were determined by a shake flask technique at 293.15–313.15 K under atmospheric pressure (≈ 85 kPa). Based on the results, type of hydrogen bond donor plays an important role in solubilization power of DESs for mesalazine; so that, the values of mesalazine solubility in betaine/EG DES + water mixtures were higher than that the other. It was also found that the solubility of mesalazine in the investigated mixtures increased by increasing mass fractions of DESs as well as enhancing temperature reaching to the maximum values in neat DESs at 313.15 K. The Hansen solubility parameters for mesalazine, neat solvents of betaine/EG or betaine/PG DESs and water were calculated to predict the solubility of drug in the investigated systems. Moreover, X-ray powder diffraction was served to analyze the equilibrium solid phase crystal of mesalazine and the results turns out that no polymorphic transformation or crystal transition during the whole solvent crystallization process. The solubility data were then represented with some cosolvency models (Jouyban-Acree, Jouyban-Acree-van’t Hoff and so on) and activity coefficient models (NRTL, Wilson and UNIQUAC). According to the calculated percentage averaged relative deviations (ARD%) for back-calculated data, all the studied models present good correlation. Additionally, an endothermic and enthalpy-driven process for mesalazine dissolution in aqueous mixtures of betaine-based DESs obtained from apparent thermodynamic analysis.

Caffeine solubility in aqueous solutions of polyethylene glycol dimethyl ether 250: measurement and thermodynamic modeling

ABSTRACT Molar solubility of caffeine in polyethylene glycol dimethyl ether 250 (PEGDME 250) + water mixtures over all mass fractions of PEGDME 250 were determined at 293.15–313.15 K under atmospheric pressure (≈ 85 kPa). The crystal forms of the caffeine in equilibrium with neat solvents of PEGDME 250 and water were analysed using X-ray powder diffraction and the results compared with the original caffeine. Also, the Hansen solubility parameters of caffeine and PEGDME 250 + water mixtures in the absence of caffeine were predicted. The studies of apparent thermodynamic analysis presented an endothermic and enthalpy-driven dissolution of caffeine. Moreover, the solubility of caffeine were correlated using various models; the van’t Hoff, mixture response surface, Jouyban–Acree, Jouyban–Acree–van’t Hoff, the modified version of Jouyban–Acree–van’t Hoff, the CNIBS/R-K, the Buchowski–Ksiazczak, the modified Wilson and modified Wilson–van’t Hoff models, acquiring average relative deviation values that were lower than 14.7%.

Solubility, Hansen solubility parameter, molecular simulation and apparent thermodynamic analysis of 5-Fluorouracil in four binary solvents

The solubility of 5-Fluorouracil (5-Fu) in four mixed solvents (methanol + THF, water + THF, 1-propanol + THF and DMF + THF) was measured by a dynamic laser monitoring at the temperature of 283.15 K − 323.15 K at 0.1 MPa. The solubility of 5-Fu increased with increasing temperature, while increased with decreasing mass-fraction of THF in each binary system. Moreover, the experimental solubility values of 5-Fu were correlated with the modified Apelblat equation, λh equation, CNIBS/R-K model and Ma model. And the average relative deviations (105RMSD) calculated by the four fitted models were all below 14.03, indicating that fitting with the four models gives satisfactory results. In addition, Hansen solubility parameters and Solute-solvent interaction can well describe the solubility behavior of 5-Fu in the four mixed solvents. Moreover, the apparent thermodynamic parameters (ΔGsolno, ΔHsolno, ΔSsolno) of 5-Fu in four binary solvents were calculated by the van’t Hoff equation. Finally, the enthalpy–entropy relationship in four mixed solvents was explained.

Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures.

This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including “water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 298.2–318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with “van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models”. The overall error values for van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10−2 in PEG-400 at 318.2 K, however the least one was 1.97 × 10−7 in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10−2) > THP (1.70 × 10−2) > 2-BuOH (1.38 × 10−2) > 1-BuOH (1.37 × 10−2) > IPA (1.10 × 10−2) > EtOH (8.37 × 10−3) > EA (8.31 × 10−3) > DMSO (7.35 × 10−3) > MeOH (3.26 × 10−3) > PG (1.88 × 10−3) > EG (1.31 × 10−3) > water (1.14 × 10−6) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was “endothermic and entropy-driven” in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility.

Thermodynamic Solubility Profile of Temozolomide in Different Commonly Used Pharmaceutical Solvents.

The solubility parameters, and solution thermodynamics of temozolomide (TMZ) in 10 frequently used solvents were examined at five different temperatures. The maximum mole fraction solubility of TMZ was ascertained in dimethyl sulfoxide (1.35 × 10−2), followed by that in polyethylene glycol-400 (3.32 × 10−3) > Transcutol® (2.89 × 10−3) > ethylene glycol (1.64 × 10−3) > propylene glycol (1.47 × 10−3) > H2O (7.70 × 10−4) > ethyl acetate (5.44 × 10−4) > ethanol (1.80 × 10−4) > isopropyl alcohol (1.32 × 10−4) > 1-butanol (1.07 × 10−4) at 323.2 K. An analogous pattern was also observed for the other investigated temperatures. The quantitated TMZ solubility values were regressed using Apelblat and Van’t Hoff models and showed overall deviances of 0.96% and 1.33%, respectively. Apparent thermodynamic analysis indicated endothermic, spontaneous, and entropy-driven dissolution of TMZ in all solvents. TMZ solubility data may help to formulate dosage forms, recrystallize, purify, and extract/separate TMZ.

Solubilization of a novel antitumor drug ribociclib in water and ten different organic solvents at different temperatures

ABSTRACT Objective This study reports new solubility and physicochemical data for ribociclib (RCB) in water and ten organic solvents including “methanol (MeOH), ethanol (EtOH), isopropyl alcohol (IPA), n-butanol (n-BuOH), propylene glycol (PG), polyethylene glycol-400 (PEG-400), acetone, ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 293.2-313.2 K and 101.1 kPa. Significance The obtained data are useful for the industrial applications of (RCB) Methods The solubility of RCB was measured and regressed using “van’t Hoff, Buchowski-Ksiazczak λh, the modified Apelblat, and Jouyban models”. Results The overall deviations of <4.0% were recorded for all four models. The maximum mole fraction solubility of RCB was 2.66 x 10−2 in PEG-400 at 313.2 K, however the lowest one was in water. The RCB solubility increased with temperature and the order followed in the water and ten different organic solvents was PEG-400 (2.66 x 10−2) > THP (1.00 x 10−2) > PG (5.39 x 10−3) > DMSO (5.00 x 10−3) > n-BuOH (3.23 x 10−3) > acetone (3.11 x 10−3) > IPA (1.58 x 10−3) > EA (1.41 x 10−3) > EtOH (1.37 x 10−3) > MeOH (8.10 x 10−4) > water (2.38 x 10−5) at 313.2 K. The maximum solute-solvent interactions were found in RCB-PEG-400 in comparison with other combination of RCB and solvents. “Apparent thermodynamic analysis” indicated an “endothermic and entropy-driven dissolution” of RCB in water and ten organic solvents. Conclusions Based on all these data and observations, PEG-400 can be used as the best co-solvent for RCB solubilization.

Solubility of Cinnarizine in (Transcutol + Water) Mixtures: Determination, Hansen Solubility Parameters, Correlation, and Thermodynamics.

Between 293.2 and 313.2 K and at 0.1 MPa, the solubility of the weak base, cinnarizine (CNZ) (3), in various {Transcutol-P (TP) (1) + water (2)} combinations is reported. The Hansen solubility parameters (HSP) of CNZ and various {(TP) (1) + water (2)} mixtures free of CNZ were also predicted using HSPiP software. Five distinct cosolvency-based mathematical models were used to link the experimentally determined solubility data of CNZ. The solubility of CNZ in mole fraction was increased with elevated temperature and TP mass fraction in {(TP) (1) + water (2)} combinations. The maximum solubility of CNZ in mole fraction was achieved in neat TP (5.83 × 10−2 at 313.2 K) followed by the minimum in neat water (3.91 × 10−8 at 293.2 K). The values of mean percent deviation (MPD) were estimated as 2.27%, 5.15%, 27.76%, 1.24% and 1.52% for the “Apelblat, van’t Hoff, Yalkowsky–Roseman, Jouyban–Acree, and Jouyban–Acree–van’t Hoff models”, respectively, indicating good correlations. The HSP value of CNZ was closed with that of neat TP, suggesting the maximum solubilization of CNZ in TP compared with neat water and other aqueous mixtures of TP and water. The outcomes of the apparent thermodynamic analysis revealed that CNZ dissolution was endothermic and entropy-driven in all of the {(TP) (1) + water (2)} systems investigated. For {(TP) (1) + water (2)} mixtures, the enthalpy-driven mechanism was determined to be the driven mechanism for CNZ solvation. TP has great potential for solubilizing the weak base, CNZ, in water, as demonstrated by these results.

Experimental Solubility of Ketoconazole, Validation Models, and In vivo Prediction in Human Based on GastroPlus.

The study aimed to identify a suitable cosolvent + water mixture for subcutaneous (sub-Q) delivery of ketoconazole (KETO). The solubility was assessed for several dimethyl acetamide (DMA) + water mixtures at T = 293.2 to 318.2 K and pressure P = 0.1 MPa. The experimental solubility (xe) was validated using the Van 't Hoff and Yalkowsky models and functional thermodynamic parameters (enthalpy ΔsolH°, entropy ΔsolS°, and Gibbs free energy ΔsolG°). The in vitro drug release study was performed at physiological pH, and the data served as the input to GastroPlus, which predicted the in vivo performance of KETO dissolved in a DMA + water cosolvent mixture for sub-Q delivery in human. The maximum solubility (mole fraction) of KETO (9.81 × 10-1) was obtained for neat DMA at 318.2 K whereas the lowest value (1.7 × 10-5) was for pure water at 293.2 K. An apparent thermodynamic analysis based on xe gave positive values for the functional parameters. KETO dissolution requires energy, as evidenced by the high positive values of ΔsolH° and ΔsolG°. Interestingly, ΔsolG° progressively decreased with increasing concentration of DMA in the DMA + water mixture, suggesting that the DMA-based molecular interaction improved the solubilization. Positive values of ΔsolG° and ΔsolS° for each DMA + water cosolvent mixture corroborated the endothermic and entropy-driven dissolution. GastroPlus predicted better absorption of KETO through sub-Q delivery than oral delivery. Hence, the DMA + water mixture may be a promising system for sub-Q delivery of KETO to control topical and systemic fungal infections.

Solubility and thermodynamic properties of piperine in (acetone/ethyl acetate + ethanol) at 278.15 K to 318.15 K and its correlation with the Jouyban-Acree and CNIBS/R-K models

The effect of cosolvent on the dissolution process for piperine is an important aspect of its purification, recrystallization and clinical application. In this work, the solubility profile of piperine in acetone + ethanol and ethyl acetate + ethanol binary solvents with acetone / ethyl acetate mass fraction ranging from 0 to 1 at various temperatures ranging from 278.15 K to 318.15 K was measured and evaluated using Jouyban-Acree model and CNIBS/R-K model. The results showed that the solubility of piperine increased firstly and then decreased with the increasing mass fraction of acetone / ethyl acetate at a certain temperature. The solute–solvent interaction was analyzed by solubility parameters. The values of RAD show that the CNIBS/R-K model is more satisfactory to correlate the experimental data. Furthermore, apparent thermodynamic analysis indicate that the dissolution is an endothermic and entropy driven process.

Solubility of sulfamerazine in (ethylene glycol + water) mixtures: Measurement, correlation, dissolution thermodynamics and preferential solvation

The equilibrium solubility of sulfamerazine (SMR) in neat ethylene glycol (EG) and nineteen {(EG) (1) + water (2)} mixtures is reported at temperatures from (278.15 to 318.15) K. Mole fraction solubility of SMR (x3) increases with temperature arising and also increases with the EG proportion increasing. It varies from 1.71 × 10−5 in neat water to 7.78 × 10−4 in neat EG at 298.15 K. Solubility behavior was correlated by the extended log-linear model of Yalkowsky, the Jouyban-Acree model, and Jouyban-Acree-van’t Hoff model and the obtained mean percentage deviations are 80.1%, 6.7% and 6.6%, respectively. From the variation of solubility with temperature, the apparent thermodynamic analysis of dissolution and mixing processes was performed in all the mixtures and neat solvents. From inverse Kirkwood-Buff integrals (IKBI) calculations is observed that SMR exhibits low negative preferential solvation parameters by EG in water-rich mixtures. Otherwise, SMR is preferentially solvated by EG in the interval (0.24 < x1 < 1.00).

Investigation on the Solubility of the Antidepressant Drug Escitalopram in Subcritical Water

Escitalopram (ESC), the S-enantiomer of citalopram, is a selective serotonin reuptake inhibitor. Escitalopram is widely used to treat panic disorder, depression, obsessive compulsive disorder, and social anxiety disorder. The main goal of this present research is to determine the aqueous solubility of ESC at temperatures ranging from 298 to 473 K and a pressure of 5.0 MPa. ESC solubility increased significantly from 1.08 × 10–3 to 59.88 × 10–3 (mole fraction) when the temperature was raised from 298 to 473 K. This is a 55-fold enhancement. A mathematical model was developed based on our experimental solubility data. The model was used to successfully predict the solubility of ESC in subcritical water. Furthermore, experimental data were correlated using a modified Apelblat equation. The apparent thermodynamic analysis including apparent dissolution standard enthalpy (ΔsolH) and apparent dissolution standard entropy (ΔsolS) were calculated. Thermodynamic property calculations showed that the process is endothermic ΔsolH > 0, and the ΔsolS values were relatively high. Spectroscopic analyses revealed that ESC was stable in subcritical water at temperatures up to 473 K. The enhanced solubility of ESC in subcritical water enabled us to use high-temperature liquid chromatography to separate this antidepressant drug.

The dissolution behavior and thermodynamic properties of amlodipine in mixtures of n-propanol/isopropanol + water

Improving the solubility of poorly water-soluble drugs is one of the biggest problems. In this study, the dissolution behavior of amlodipine in aqueous mixtures of co-solvents including n-propanol and isopropanol within the temperature range from 273.15 K to 313.15 K was investigated and presented by Jouyban-Acree model. In n-propanol (1) + water (2) binary mixtures, the maximum mole fraction solubility of amlodipine (3.546 × 10-2) was observed at 313.15 K when the mass fraction of n-propanol was 0.80. The corresponding data (2.714 × 10-2) for isopropanol (1) + water (2) systems was obtained with the mass fraction of 0.60 for isopropanol at 313.15 K. The maximum data for water was (2.245 × 10-5) at 313.15 K, an about 1.580 × 103 fold increase in n-propanol + water binary mixtures, and 1.209 × 103 fold increase in isopropanol + water systems. The co-solvency behavior of amlodipine in two aqueous solutions was analyzed by acidic partial solubility parameter (δ1a), basic partial solubility parameter (δ1b) and Hildebrand solubility parameter (δ1). The positive coefficient of δ1 and δ1a related to favorable nonspecific and specific interactions, respectively. Moreover, amlodipine behaves as Lewis base toward n-propanol + water and isopropanol + water binary mixtures. Besides, the outcomes of the “apparent thermodynamic analysis” showed that the dissolution of amlodipine was endothermic and entropy-driven in all composition of n-propanol + water and isopropanol + water binary mixtures.

Solubilization and thermodynamic properties of simvastatin in various micellar solutions of different non-ionic surfactants: Computational modeling and solubilization capacity.

The aim of this work was to solubilize simvastatin (SIM) using different micellar solutions of various non-ionic surfactants such as Tween-80 (T80), Tween-20 (T20), Myrj-52 (M52), Myrj-59 (M59), Brij-35 (B35) and Brij-58 (B58). The solubility of SIM in water (H2O) and different micellar concentrations of T80, T20, M52, M59, B35 and B58 was determined at temperatures T = 300.2 K to 320.2 K under atmospheric pressure p = 0.1 MPa using saturation shake flask method. The experimental solubility data of SIM was regressed using van’t Hoff and Apelblat models. The solubility of SIM (mole fraction) was recorded highest in M59 (1.54 x 10−2) followed by M52 (6.56 x 10−3), B58 (5.52 x 10−3), B35 (3.97 x 10−3), T80 (1.68 x 10−3), T20 (1.16 x 10−3) [the concentration of surfactants was 20 mM in H2O in all cases] and H2O (1.94 x 10−6) at T = 320.2 K. The same results were also recorded at each temperature and each micellar concentration of T80, T20, M52, M59, B35 and B58. “Apparent thermodynamic analysis” showed endothermic and entropy-driven dissolution/solubilization of SIM in H2O and various micellar solutions of T80, T20, M52, M59, B35 and B58.

Solubilization, Hansen solubility parameters, and thermodynamic studies of delafloxacin in (transcutol + 1-butyl-3-methyl imidazolium hexafluorophosphate) mixtures

The solubilization, Hansen solubility parameters (HSPs), and thermodynamic properties of delafloxacin (DLN) in various unique combination of Transcutol-HP® (THP) and 1-butyl-3-methyl imidazolium hexafluorophosphate ionic liquid (BMIM-PF6) mixtures were evaluated for the first time in this research. The ‘mole fraction solubilities (x 3)’ of DLN in different (THP + BMIM-PF6) compositions were determined at ‘T = 298.2–318.2 K’ and ‘p = 0.1 MPa’. The HSPs of DLN, neat THP, neat BMIM-PF6, and binary (THP + BMIM-PF6) compositions free of DLN were also determined. The x 3 data of DLN was regressed using ‘van’t Hoff, Apelblat, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-van’t Hoff models’ with overall error values of less than 3.0%. The highest and lowest x 3 value of DLN was recorded in neat THP (5.48 × 10−3 at T = 318.2 K) and neat BMIM-PF6 (6.50 × 10−4 at T = 298.2 K), respectively. The solubility of DLN was found to be enhanced significantly with an arise in temperature in all (THP + BMIM-PF6) compositions including pure THP and pure BMIM-PF6. However, there was slight increase in DLN solubility with increase in THP mass fraction in all (THP + BMIM-PF6) mixtures. The HSP of pure THP and pure BMIM-PF6 were found very close to each other, suggesting the great potential of both solvents in DLN solubilization. The maximum solute-solvent interactions at molecular level were recorded in DLN-THP compared to DLN-BMIM-PF6. An ‘apparent thermodynamic analysis’ study indicated an ‘endothermic and entropy-driven dissolution’ of DLN in all (THP + BMIM-PF6) compositions including neat THP and BMIM-PF6.

Experimental Solubility, Thermodynamic/Computational Validations, and GastroPlus-Based In Silico Prediction for Subcutaneous Delivery of Rifampicin.

We focused to explore a suitable solvent for rifampicin (RIF) recommended for subcutaneous (sub-Q) delivery [ethylene glycol (EG), propylene glycol (PG), tween 20, polyethylene glycol-400 (PEG400), oleic acid (OA), N-methyl-2-pyrrolidone (NMP), cremophor-EL (CEL), ethyl oleate (EO), methanol, and glycerol] followed by computational validations and in-silico prediction using GastroPlus. The experimental solubility was conducted over temperature ranges T = 298.2-318.2 K) and fixed pressure (p = 0.1 MPa) followed by validation employing computational models (Apelblat, and van't Hoff). Moreover, the HSPiP solubility software provided the Hansen solubility parameters. At T = 318.2K, the estimated maximum solubility (in term of mole fraction) values of the drug were in order of NMP (11.9 × 10-2) ˃ methanol (6.8 × 10-2) ˃ PEG400 (4.8 × 10-2) ˃ tween 20 (3.4 × 10-2). The drug dissolution was endothermic process and entropy driven as evident from "apparent thermodynamic analysis". The activity coefficients confirmed facilitated RIF-NMP interactions for increased solubility among them. Eventually, GastroPlus predicted the impact of critical input parameters on major pharmacokinetics responses after sub-Q delivery as compared to oral delivery. Thus, NMP may be the best solvent for sub-Q delivery of RIF to treat skin tuberculosis (local and systemic) and cutaneous related disease at explored concentration.

Thermodynamic, Computational Solubility Parameters in Organic Solvents and In Silico GastroPlus Based Prediction of Ketoconazole.

The study aimed to select a suitable solvent capable to solubilize ketoconazole (KETO) and serve as a permeation enhancer across the skin. Experimental solubility and Hansen solubility parameters were obtained in ethanol, dimethyl sulfoxide (DMSO), ethylene glycol, oleic acid, span 80, limonene, eugenol, transcutol (THP), labrasol, and propylene glycol. Thermodynamic functional parameters and computational models (vanʼt Hoff and Apelblat) validated the determined solubility in various solvents at T = 298.2 K to 318.2 K and P = 0.1 MPa. The HSPiP software estimated the solubility parameters in the solvents. The maximum mole fractional solubility values of KETO were found to be in an order as oleic acid (8.5 × 10–3) > limonene (7.3 × 10–3) > span 80 (6.9 × 10–2) > THP (4.9 × 10–2) > eugenol (4.5 × 10–3) at T = 318.2 K. The results of the apparent thermodynamic analysis confirmed that the dissolution rate was endothermic and entropy driven. The GastroPlus program predicted significantly high permeation of KETO (79.1%) in human skin from the KETO-THP construct as compared to drug solution (38%) and excellent immediate release from THP-solubilized construct (90% < 1 h). Hence, THP could be a better option for topical, transdermal, and oral formulation.