Estimation of critical point, vapor pressure and heat of sublimation of pharmaceuticals and their solubility in supercritical carbon dioxide (original) (raw)
Related papers
Solubility of pharmaceutical compounds in supercritical carbon dioxide
The Journal of Supercritical Fluids, 2012
The solubility of pharmaceutical solid compounds in supercritical carbon dioxide is of great importance in a wide range of applications that include: development of drug delivery systems, powder processing, and precipitation/crystallization processes.
Journal of the Serbian Chemical Society, 2019
In the present study, the effect of equations of state and mixing rules in a thermodynamic approach has been investigated for the correlation of the solubility of four new solid pharmaceutical compounds, namely, benzamide, cetirizine, metaxalone and niflumic acid in supercritical CO 2 at different temperatures and pressures. Two equations of state, the Peng-Robinson (PR) and Soave-Redlich-Kwong (SRK), coupled with mixing rules of one-parameter van der Waals (vdW1) and two-parameter van der Waals (vdW2) were used, where the binary interaction parameters for these sets of equations were evaluated. The approach correlations and the robustness of the numerical technique were validated with the experimental data previously reported for these compounds at different temperatures and pressures. The calculated average absolute relative deviations (AARD) were 7.51 and 5.31 % for PR/vdW1 and PR/ /vdW2 couples, and 11.05 and 10.24 % for SRK/vdW1 and SRK/vdW2 couples, respectively. It was also found that the PR equation of state results in modeling performance better than the SRK equation, and the vdW2 mixing rule better than the vdW1 one. These results obviously demonstrate that the combined approach used in this study is applicable for correlation of solid solubilities of some pharmaceutical compounds in supercritical CO 2. Additionally, a semi-empirical correlation is proposed for estimating the solubility of drug solids in supercritical CO 2 as a function of pressure and temperature.
Journal of Molecular Liquids, 2024
Determining the dissolution characteristics of medicines in supercritical CO2 is vital for formulating innovative drug delivery systems through an efficient supercritical process. This study investigates the solubility of three poorly bioavailable drugs −Topiramate, Meclizine, and Dimenhydrinate- in supercritical CO2, both with and without ethanol co-solvent, over a temperature range of 308 K to 348 K and pressures from 17 MPa to 41 MPa. The solubility of these medicines in supercritical CO2 (binary system) is notably low, ranging from 2.5 × 10-6 − 4.54 × 10-6, 0.26 × 10-5 − 2.3 × 10-5, and 0.20 × 10-5 − 1.91 × 10-5 in mole fraction, respectively. However, in the presence of ethanol (ternary system), their supercritical solubility significantly increases by factors of 2.75–5.84, 1.40–3.20, and 2.04–4.85, respectively. The supercritical solubility of the mentioned compounds are theoretically evaluated using several approaches, including empirical models, a machine learning methodology employing a multilayer perceptron neural network, thermodynamic models based on two cubic equations of state (Peng-Robinson (PR) and Soave–Redlich–Kwong (SRK)), and a non-cubic equation of state (perturbed chain-statistical associating fluid theory (PC-SAFT)), as well as two expanded liquid models (UNIQUAC and Wilson). The findings revealed that all the specified models demonstrate acceptable accuracy in correlating the experimental data of the specified drugs in both binary and ternary systems. Among these, the PR and SRK thermodynamic models, along with some empirical models, show the best results. Furthermore, the machine learning model exhibited outstanding accuracy in forecasting the supercritical solubility of the desired drugs, with over 99.9% alignment between their predicted and experimental data.
Journal of the Serbian Chemical Society, 2019
In the present study, the effect of equations of state and mixing rules in a thermodynamic approach has been investigated for the correlation of the solubility of four new solid pharmaceutical compounds, namely, benzamide, cetirizine, metaxalone and niflumic acid in supercritical CO2 at different temperatures and pressures. Two equations of state, the Peng?Robinson (PR) and Soave?Redlich?Kwong (SRK), coupled with mixing rules of one-parameter van der Waals (vdW1) and two-parameter van der Waals (vdW2) were used, where the binary interaction parameters for these sets of equations were evaluated. The approach correlations and the robustness of the numerical technique were validated with the experimental data previously reported for these compounds at different temperatures and pressures. The calculated average absolute relative deviations (AARD) were 7.51 and 5.31 % for PR/vdW1 and PR/ /vdW2 couples, and 11.05 and 10.24 % for SRK/vdW1 and SRK/vdW2 couples, respectively. It was also fo...
Scientific Reports
Understanding the drug solubility behavior is likely the first essential requirement for designing the supercritical technology for pharmaceutical processing. Therefore, this study utilizes different machine learning scenarios to simulate the solubility of twelve non-steroidal anti-inflammatory drugs (NSAIDs) in the supercritical carbon dioxide (SCCO2). The considered NSAIDs are Fenoprofen, Flurbiprofen, Ibuprofen, Ketoprofen, Loxoprofen, Nabumetone, Naproxen, Nimesulide, Phenylbutazone, Piroxicam, Salicylamide, and Tolmetin. Physical characteristics of the drugs (molecular weight and melting temperature), operating conditions (pressure and temperature), and solvent property (SCCO2 density) are effectively used to estimate the drug solubility. Monitoring and comparing the prediction accuracy of twelve intelligent paradigms from three categories (artificial neural networks, support vector regression, and hybrid neuro-fuzzy) approves that adaptive neuro-fuzzy inference is the best too...
Solubility of Anti-Inflammatory Drugs in Supercritical Carbon Dioxide
Journal of Chemical and Engineering Data, 1996
Supercritical fluid extraction is a potential technique for the purification of pharmaceutical products containing residual solvents. The solubilities of the drugs in supercritical carbon dioxide are being measured as part of a program in which the potential applications of this technology are being investigated. The solubilities of three inhibitors of inflammatory activity, Ketoprofen, Piroxicam, and Nimesulide, in supercritical CO 2 , measured using a dynamic saturation technique, are reported at pressures between 100 bar and 220 bar and at two temperatures: 312.5 K and 331.5 K. These chemicals have relatively high solubilities with values ranging from 4 × 10 -6 to 15 × 10 -4 mole fraction. The solubilities exhibit a clear dependence on the solvent density, and this has been used to provide a simple and precise correlation of the data.
Comptes Rendus Chimie, 2017
A novel density-based model derived by a simple modification of the Jouyban et al. model has been proposed to correlate the solubility of solid drugs in supercritical carbon dioxide. The six-parameter model expresses the solubility only as a function of the solvent density and the equilibrium temperature. This model is in contrast to the Jouyban et al. (J. Superiority. Fluids 24 (2002) 19) model, which gives the solubility as a function of the solvent density and the equilibrium temperature and pressure. The performance of the model has been tested on a database of 100 drugs that account for 2891 experimental data points collected from the literature. The comparison in terms of the mean absolute relative deviation for each solid drug and for the entire database between the proposed model and models that have been suggested to be mostly more accurate demonstrates that the proposed model has the best global correlation performance, exhibiting an overall average absolute relative deviation of 8.13%.
The Journal of Supercritical Fluids, 2013
Since the knowledge of pharmaceutical solubilities in the supercritical carbon dioxide is one of the first essential necessities for designing the supercritical carbon dioxide-based processes, solubility of piroxicam a non-steroidal anti-inflammatory drug was experimentally measured. In this regard, a static method coupled with gravimetric method was used to measure the solubility of piroxicam in the supercritical carbon dioxide in temperature and pressure range of 308.15 K to 338.15 K and 16 MPa to 40 MPa, respectively. The obtained solubility data were in the range of 1.17×10-5 and 5.12×10-4 based on the mole fraction (mole piroxicam/ (mole piroxicam + mole CO 2)) then modeled using four different density based correlations namely Bartle et al., Mendez-Santiago-Teja, Chrastil and Kumar and Johnston models. The results of error analysis revealed that the used correlations were potential to correlate the solubility of piroxicam with minimum and maximum average absolute relative deviation percents (AARD %) of 14.4 % and 15.2 %, respectively.
Loxoprofen Solubility in Supercritical Carbon Dioxide: Experimental and Modeling Approaches
Journal of Chemical & Engineering Data, 2020
MPa) in supercritical carbon dioxide (SC-CO 2). The solubility data were measured using a gravimetric-based approach and revealed the solubility range of 1.35 × 10 −5 to 1.28 × 10 −3 based on the mole fraction of loxoprofen. The results revealed that solubility can be significantly enhanced from 1.04 × 10 −5 to 1.28 × 10 −3 (mole fraction basis) for the isotherm at 338 K because of the effect of temperature which can boost the pressure effect on solubility enhancement, at pressures greater than crossover (around 20 MPa for the case of loxoprofen). Moreover, the experimental data points were modeled using five different density-based correlations including Chrastil, Garlapati and Madras, Mendez-Santiago and Teja (MST), Bartle et al., and Kumar and Johnston (K−J) models because measuring the solubility of loxoprofen in entire required ranges of pressure and temperature is impossible or expensive similar to the other pharmaceuticals. The results of modeling revealed that one can correlate the loxoprofen solubility data with an accuracy of about 9.2% (Mendez-Santiago−Teja), 10.7% (Bartle et al.), 7.1% (Kumar and Johnstone), 12.7% (Chrastil), and 12.7% (Garlapati and Madras) based on average absolute relative deviation percent (AARD %).
Solubility of ketoprofen in supercritical carbon dioxide
The Journal of Supercritical Fluids, 2012
In the present study, solubility of ketoprofen in the supercritical carbon dioxide was measured experimentally using gravimetric method. In this direction the temperature and pressure was ranged between 308.15-338.15 K and 160-400 bar, respectively. The obtained solubilites revealed that the ketoprofen solubility was in the range of 2.21 × 10 −5 to 7.12 × 10 −4 mole fraction according to the different temperatures and pressures. Measured solubilites demonstrated that pressure and temperature have a direct effect on the solubility enhancement. Finally, the least square method and curve fitting approaches were utilized to find the fitting parameters of four semi-empirical density based correlations including Mendez-Santiago-Teja, Bartle, Chrastile and Kumar and Johnston methods. The results revealed that Bartle et al. method was able to correlate the ketoprofen solubility with a minimum average absolute relative deviation (AARD %) of 5.95%.