Solubility Data Research Articles

Determination of 5-fluorouracil anticancer drug solubility in supercritical CO2using semi-empirical and machine learning models

In order to provide the facilities to design the supercritical fluid (SCF) processes for micro or nanosizing of solid solute compounds such as drugs, it is essential to obtain their solubility in green solvents like pressurized CO2. This important role is the first stage for assessing each SCF technology. A statistical method was developed for the first time and employed to determine 5-fluorouracil (5-Fu) solubility. The measurements were performed at different pressures (120–270 bar) and temperatures (308–338 K) through UV-vis spectrophotometry, for the first time. The solubility was obtained between 0.0024 and 0.0176 g/L. The 5-Fu mole fraction at constant temperature, increases with an increase in pressure. Whereas, a crossover point has been seen. Three models with different approaches were applied to correlate and model the experimental data set: (i) seven density-based models, (ii) PR equations of state (vdW2 mixing rule), and (iii) machine learning-based models, namely non-linear regressions, Random Forest, Gradient Boosting, Decision Tree, and Kernel Ridge. All tested models successfully correlate and model the solubility data within an acceptable accuracy. Meanwhile, the empirical model suggested by Sodeifian model 2, is superior with the lowest AARD% (AARD = 4.12%). Finally, total, solvation, and vaporization enthalpies of the drug/Sc-CO2 binary system were determined using semi-empirical correlations, for the first time.

COCOMO2: A Coarse-Grained Model for Interacting Folded and Disordered Proteins.

Biomolecular interactions are essential in many biological processes, including complex formation and phase separation processes. Coarse-grained computational models are especially valuable for studying such processes via simulation. Here, we present COCOMO2, an updated residue-based coarse-grained model that extends its applicability from intrinsically disordered peptides to folded proteins. This is accomplished with the introduction of a surface exposure scaling factor, which adjusts interaction strengths based on solvent accessibility, to enable the more realistic modeling of interactions involving folded domains without additional computational costs. COCOMO2 was parametrized directly with solubility and phase separation data to improve its performance on predicting concentration-dependent phase separation for a broader range of biomolecular systems compared to the original version. COCOMO2 enables new applications including the study of condensates that involve IDPs together with folded domains and the study of complex assembly processes. COCOMO2 also provides an expanded foundation for the development of multiscale approaches for modeling biomolecular interactions that span from residue-level to atomistic resolution.

Mesalazine solubility in supercritical carbon dioxide with and without cosolvent and modeling

In this study, the solubility of mesalazine in supercritical carbon dioxide with and without cosolvent was carried out for the first time at different temperatures and pressure values ranging from 308 to 338 K and 12 to 30 MPa, respectively. The determined experimental molar solubilities of mesalazine in supercritical carbon dioxide were in the range of 4.41 × 10–5 to 9.97 × 10–5 (308 K), 3.9 × 10–5 to 13.1 × 10–5 (318 K), 3.4 × 10–5 to 16 × 10–5 (328 K) and 3.3 × 10–5 to 18.4 × 10–5 (338 K). Meanwhile, the determined experimental molar solubilities in supercritical carbon dioxide using 2% dimethyl sulfoxide as cosolvent were in the range of 28.22 × 10–5 to 36.2 × 10–5 (308 K), 26.07 × 10–5 to 51.41 × 10–5 (318 K), 25.02 × 10–5 to 69.07 × 10–5 (328 K) and 25.86 × 10–5 to 82.6 × 10–5 (338 K). A novel association model was employed to simulate the solubility data of the binary and ternary systems. Various semiempirical correlations were utilized to calculate the solubility of mesalazine in supercritical carbon dioxide. The new association model was deemed the most superior model, achieving an average absolute relative deviation value of 4.13% without a cosolvent, and 3.36% when a cosolvent was included.

Abraham model expressions for correlating and predicting solubilities and molar solubility ratios of crystalline nonelectrolyte organic compounds in dibutyl adipate

ABSTRACT Abraham model correlations have been derived for solute transfer into the dibutyl adipate mono-solvent from both water and from the gas phase based on spectrophotometric solubility measurements for a chemically diverse set of 33 different crystalline organic compounds covering a wide range of polarity and hydrogen-bonding characteristics. The derived Abraham model correlations describe the observed molar solubility data to within an overall standard deviation of 0.13 log units. Comparison of the reported dibutyl adipate equations with those previously determined for dimethyl adipate reveal that the respective equations for both dialkyl adipate mono-solvents are essentially identical, at least to within the coefficient’s combined standard error.

FORMULATION AND EVALUATION OF AN ORAL TIMED PULSATILE DRUG DELIVERY FOR ALLEVIATING PAIN IN RHEUMATOID ARTHRITIS

Objective: The present study was aimed to formulate and evaluate an oral timed-release pulsatile drug delivery of AcecloFenac (AF) for rheumatoid arthritis pain by the Chronopharmaceutical approach with early morning breakthrough of AF as analgesic and anti-inflammatory agent for the treatment of rheumatoid arthritis. Methods: A solubility was enhanced by formulating it as a self-emulsified system with a suitable oil and surfactant mixture. The interaction between the drug and the excipient was examined using Fourier Transform Infra-Red (FTIR) spectroscopy. The prepared formulation consists of 2 different parts: The basic design consists of burst-release core tablets with solid self-emulsified AF by using different super disintegrants, and the press-coating of optimised tablets by using different compositions of Ethylcellulose (hydrophobic) and Hydroxy Propyl Methyl Cellulose (HPMC K100) (hydrophilic) polymers. Results: FTIR studies revealed no interaction between drug and excipients. From the solubility data, suitable oil and surfactants were selected. Pseudo-ternary plots help in finding of suitable surfactant mixtures for solid self-emulsified AF. Core tablets were evaluated for pre-compression characteristics, disintegration time, drug content, weight variation, hardness, friability, thickness, and % drug release. Among all solid self-emulsified formulations, S1C6 is successful, with 98.88% drug release in 20 min. The compression coat formulations were also evaluated for Hardness, weight variation, thickness, lag time, and in vitro drug release profile. Among them, F4 was optimised by its suitable lag time and drug release of 97.23% at the end of 6 h. Conclusion: The system released the drug after a predetermined lag time of 4 h and thus, the dosage form can be taken at bedtime so that the drug will be released when the symptoms are prominent. Nine formulations were prepared, of which F4 formulation showed the highest drug release of 97.23 % at the end of 6 h and showed compliance with the chronotherapeutic objective of rheumatoid arthritis.

Safety of mineral salt containing potassium and magnesium as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on a mineral salt, containing potassium and magnesium, as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a mineral salt that consists mainly of magnesium potassium trichloride hexahydrate. The information provided on the composition is sufficient for characterising the NF and does not raise safety concerns. The production process is sufficiently described and does not raise safety concerns. The NF is intended to be added to meat, sausages and dishes based on pasta, rice and other cereals. Taking into account the composition of the NF and the proposed use and use levels, the Panel considers that the consumption of the NF is not nutritionally disadvantageous. Regarding the presence of bromide in the NF, the Panel notes that the combined daily intake of bromide from the NF and the background diet does not exceed the tolerable daily intake of bromide of 0.4 mg/kg body weight (bw) per day. Based on its physicochemical characteristics and solubility data, the NF is expected to be dissociated in the gastrointestinal tract. Taking into account the composition and the nature of the NF, the Panel considers that no toxicological studies with the NF are required. The Panel concludes that the NF (i.e. a mineral salt containing potassium and magnesium) is safe under the proposed conditions of use.

Real-world application of PBPK in drug discovery.

The utility of PBPK models in support of drug development has been well documented. During the discovery stage, PBPK has increasingly been applied for early risk assessment, prediction of human dose, toxicokinetic dose projection and early formulation assessment. Previous review articles have proposed model building and application strategies for PBPK-based first in human predictions with comprehensive descriptions of the individual components of PBPK models. This includes the generation of decision trees, based on comprehensive literature reviews, to guide the application of PBPK in the discovery setting. The goal of this mini review is to provide additional guidance on the real-world application of PBPK, in support of the discovery stage of drug development. In this mini review, our goal is to provide guidance on the typical steps involved in the development and application of a PBPK model during drug discovery to assist in decision making. We have illustrated our recommended approach through description of case examples, where PBPK has been successfully applied to aid in human PK projection, candidate selection and prediction of drug interaction liability for parent and metabolite. Through these case studies, we have highlighted fundamental issues, including pre-verification in preclinical species, the application of empirical scalars in the prediction of in vivo clearance from in vitro systems, in silico prediction of permeability and the exploration of aqueous and biorelevant solubility data to predict dissolution. In addition, current knowledge gaps have been highlighted and future directions proposed. Significance Statement Through description of three case studies, we have highlighted the fundamental principles of PBPK application during drug discovery. These include pre-verification of the model in preclinical species, application of empirical scalars where necessary in the prediction of clearance, in silico prediction of permeability, and the exploration of aqueous and biorelevant solubility data to predict dissolution. In addition, current knowledge gaps have been highlighted and future directions proposed.

Adsorption kinetics and solubilisation of ciprofloxacin in quaternary ammonium-based surface-active compounds: experimental and computational study.

The adsorption and aggregation of amphiphiles at different solvent interfaces are of great scientific and technological importance. In this study, interfacial tension measurements of surface-active compounds-ionic liquid 2-dodecyl-2,2dimethylethanolammonium bromide (12Cho.Br) and cationic surfactant cetyltrimethylammonium bromide (CTAB)-were conducted both in the absence and presence of ciprofloxacin (CIP). Equilibrium interfacial tension (EIFT) measurements and conductivity data demonstrate the effect of CIP on the critical micellar concentration and surface excess concentration of 12Cho.Br and CTAB. Additionally, dynamic interfacial tension (DIFT) measurements were performed to compare the interfacial tension of pure 12Cho.Br and CTAB solutions, as well as those in the presence of the drug (with and without 0.3% acetic acid), as a function of time. The DIFT analysis revealed that the adsorption of 12Cho.Br and CTAB at the air-water interface followed a mixed diffusion-adsorption controlled mechanism. The adsorption processes of 12Cho.Br and CTAB molecules were studied over short time intervals (t → 0) and longer time intervals (t → ∞). The adsorption behaviour was correlated with concentration and the presence of energy barriers. In the presence of CIP, the diffusion coefficient was compared to that of the pure 12Cho.Br and CTAB systems to assess its effect on adsorption and to validate the participation of CIP in DIFT relaxations. Additionally, DIFT measurements were employed to investigate CIP solubility in different SAC systems. Data from the relaxation profiles across a range of concentrations were used to determine the solubility limit of the drug molecules. The solubility data obtained from DIFT correlates strongly with the UV spectroscopy results. Furthermore, DFT calculations provide insights into the frontier orbital structures and physicochemical parameters of complex formations.

Hierarchical Graph Attention Network with Positive and Negative Attentions for Improved Interpretability: ISA-PN.

With the advancement of deep learning (DL) methods in chemistry and materials science, the interpretability of DL models has become a critical issue in elucidating quantitative (molecular) structure-property relationships. Although attention mechanisms have been generally employed to explain the importance of molecular substructures that contribute to molecular properties, their interpretability remains limited. In this work, we introduce a versatile segmentation method and develop an interpretable subgraph attention (ISA) network with positive and negative streams (ISA-PN) to enhance the understanding of molecular structure-property relationships. The predictive performance of the ISA models was validated using data sets for aqueous solubility, lipophilicity, and melting temperature, with a particular focus on evaluating interpretability for the aqueous solubility data set. The ISA-PN model enables the quantification of the contributions of molecular substructures through positive and negative attention scores. Comparative analyses of the ISA, ISA-PN, and GC-Net (group contribution network) models demonstrate that the ISA-PN model significantly improves interpretability while maintaining similar accuracy levels. This study highlights the efficacy of the ISA-PN model in providing meaningful insights into the contributions of molecular substructures to molecular properties, thereby enhancing the interpretability of DL models in chemical applications.

Unlocking the potential: SLU-PP-332 and the future of exercise Enhancement and Metabolic health

The synthetic oestrogen receptor-related orphan receptor (ERR) agonist SLU-PP-332 exhibits promising potential in revolutionizing fitness and weight loss strategies. Through its activation of ERRs, SLU-PP-332 enhances energy expenditure, increases fatty acid oxidation, and reduces fat mass buildup. Studies indicate its ability to mimic exercise-induced metabolic pathways, resulting in improved endurance and weight loss in mice. While long-term implications are yet to be fully understood, initial trials show no significant adverse effects. SLU-PP-332 targets ERRs found in various human organs, influencing vital metabolic processes. With implications for treating metabolic disorders like obesity, type 2 diabetes, and heart failure, SLU-PP-332 emerges as a novel therapeutic agent. Its biological activity, structure, and solubility data support its potential as a small molecule drug in endocrinology and metabolic diseases. Further research is warranted to elucidate its long-term effects and refine its structure for future clinical applications

Determination of Solubility and Metastable Zone of Sodium Hypophosphite and Nucleation Kinetics

AbstractTo obtain thermodynamic and kinetic data of sodium hypophosphite, such as solubility and metastable zone, respectively, the solubility data for sodium hypophosphite in the temperature range of 298.15–373.15 K were obtained using a dynamic method. These data were then fitted to the Apelblat and Van't Hoff equations, and the corresponding model parameters were determined. The effects of stirring intensity and cooling rate on the width of the metastable zone of sodium hypophosphite in water were studied. The findings indicated that an increase in stirring intensity reduced the width of the metastable zone, whereas an increase in cooling rate resulted in its widening. The self‐consistent NýVlt and Sangwal metastable zone models were employed to calculate nucleation dynamic parameters in conjunction with classical nucleation theory. The results showed that the nucleation order was 2.311–3.361 over the investigated temperature range. 316.15 K is the critical temperature point at which sodium hypophosphite transforms into a dominant nucleation mode. The solid–liquid interface tension decreased rapidly with the increase of saturation temperature, and the solid–liquid interface tension is 1.167–2.638 mJ m−2.

Effect of temperature on the solubility of xonotlite

Xonotlite forms under hydrothermal conditions and it dehydrates to β-wollastonite between 770 and 800 °C under atmospheric pressure. The solubility of xonotlite is poorly known, as the experimental datasets reported in literature differ by as much as 10 log units. This study investigates the impact of temperature (7, 20, 50 and 80 °C) on the solubility of xonotlite by dissolution experiments from undersaturation. The derived solubility data are comparable to those reported in literature at 25 °C for synthesized xonotlite, while the much higher solubility reported in literature for natural xonotlite seems to describe the solubility of amorphous C-S-H. The solubility of xonotlite increases moderately at lower temperature. At 7 °C, xonotlite was found to co-exist with tobermorite.

Determining the solubility parameter and thermodynamic properties of beta-carotene in superheated water solvent by experimental and MD simulation methods

In this study, for the first time, the solubility of beta-carotene in green solvent was simulated using the molecular dynamics method. Superheated water was used as a solvent. The simulations were performed at different temperatures and a constant pressure of 2 MPa using Lammps software. The behavior of beta-carotene in solvent was investigated. The results showed that the dissolution process of beta-carotene in superheated water is endothermic and non-spontaneous, and increasing the temperature increases the dissolution of beta-carotene in superheated water. To ensure the results, the solubility of beta-carotene in superheated water was calculated using the static experimental method. The absolute average relative deviation between simulated and experimental beta-carotene solubility data in superheated water was 14.5 %. By increasing the temperature to 408.15 K, water under pressure became a solvent with the same behavior as organic solvents, and the solubility of beta-carotene, which was a lipophilic and insoluble compound in water, increased by about 80 times compared to ambient temperature. Accurately determining the solubility of this valuable medicinal plant in a green solvent can be used in the wide production of pharmaceutical, food, and cosmetic products.

Reformulated Mathematical Models for Correlating the Solubility of Solid Drugs in Supercritical Carbon Dioxide

Solubility is the fundamental thermodynamic key parameter influencing supercritical technology in practice. In the literature, several solubility models are available to represent the solubility data. They are classified into several categories based on their origin and the background on which they were developed. Some important categories of solubility models are solvate complex models, mathematical models, and phase equilibrium models. Among them, mathematical models have shown good correlation efficiency for several solute-solvent systems. However, some do not comply with the fundamental phase rule in their functional form, which can cause them to be termed redundant models. Therefore, the current investigation aims to address the redundant nature of some mathematical models. Models considered in the work relate solubility as a function of temperature, pressure, and density in a nonlinear relationship (i.e., y2 = f (T, P, ρ1)). Reformulation was aimed at converting solubility models to a dimensionally consistent form in which the mole fraction of the solute is represented as a function of the reduced density of the solvent and the reduced temperature. Thus, all solubility models considered in the work are converted to y2 = f(Tr, ρr). Further, existing models and reformulation models were tested with four standard solute-solvent systems namely, naphthalene-SCCO2, anthracene-SCCO2, phenanthrene-SCCO2, and salicylic acid-SCCO2. Finally, the comparison between the existing and the reformulated models was done in terms of global values of AARD%, R2, R2adj, and ΔΑΙC. From the results, it is quite clear that reformulated models are showing better results than the existing models.

Thermodynamic Modeling of an Aqueous N, N-Dimethyldipropylenetriamine and Benzylamine Blend for Efficient CO2 Capture.

This study evaluates the carbon dioxide (CO2) capture capabilities of a novel aqueous blend of N,N-dimethyldipropylenetriamine (DMDPTA) and benzylamine (BA). The solvent properties such density, vapor- liquid equilibrium (VLE) of CO2 in the solvent, CO2 absorption enthalpy are evaluated experimentally for solvent composition of (5 mass % DMDPTA+25 mass % BA), (10 mass % DMDPTA+20 mass % BA), and (15 mass % DMDPTA+15 mass % BA). Solvent density were measured in the temperature range of 303 K-333 K and correlated using Redlich-Kister excess molar volume model, with a low average absolute relative deviation (AARD) of 0.014. VLE data was measured using a custom-made stirred VLE cell, within CO2 partial pressure range of 2-200 kPa and at temperatures 313 K, 323 K and 333 K. Equilibrium CO2 solubility data were correlated using a modified Kent-Eisenberg model, achieving an AARD of 1.5 %. Enthalpy of CO2 absorption was measured at 313 K using a Meter Toledo reaction calorimeter. Results indicated that under similar process conditions and solvent composition, (DMDPTA+BA) blends exhibited significantly higher CO2 loading and low absorption enthalpy compared to aqueous BA and monoethanolamine solvent alone indicating the potential of (DMDPTA+BA) blend as efficient CO2 capture solvent.

Toward nanosuspension preparation by modeling the solubility of levofloxacin and ofloxacin in ethanol + water solvent mixtures at different temperatures

The present study was conducted to assess the solubility of levofloxacin and ofloxacin in different mono- and mixed solvent systems at different temperatures to provide an experimental basis for the preparation of levofloxacin and ofloxacin nanosuspensions. To this end, the solubility of both compounds was evaluated using a solid–liquid equilibrium technique in DMSO, acetone, ethanol, NMP, and water monosolvents and ethanol–water mixed solvents at different volume fractions and temperatures. The modified versions of the van’t Hoff and Gibbs equations were recruited to calculate the thermodynamic properties of the solutions. The correlation between the solubility data of levofloxacin and ofloxacin and different mathematical models, including the Yalkowsky, Jouyban-Acree, and van’t Hoff models and their combinations was studied. According to the results, the highest and lowest solubility of levofloxacin and ofloxacin were attainable in 1 (pure ethanol monosolvent) and 0.1 v/v of ethanol fractions in ethanol/water mixed solvent. Moreover, the solubility of both compounds was superior at higher temperatures. Afterwards, the nanosuspensions were prepared using the solvent-antisolvent method. Different characterization techniques revealed the formation of the smallest particles with relatively irregular morphology in the 0.1 v/v volume fraction of ethanol in water. The XRD analysis exhibited the typical crystalline diffractions of levofloxacin and ofloxacin and the thermal transitions and stability of both compounds were investigated using DSC and TGA techniques. The results obtained in this study could be used to enhance the solubility and bioavailability of levofloxacin and ofloxacin during the drug formulation development and manufacturing processes.

Testing the prediction capability of trained models: sildenafil citrate solubility in propylene glycol and 1-propanol mixtures at different temperatures

ABSTRACT This study investigates the thermodynamic characteristics, equilibrium solubility, and solvation dynamics of sildenafil citrate within binary solvent systems composed of propylene glycol and 1-propanol. Utilizing both determination and computational approaches, the solubility patterns of sildenafil citrate were quantitatively assessed, revealing direct proportionality with increments in temperature and the concentration of propylene glycol. A comparative analysis using three distinct mathematical models to represent the solid–liquid phase equilibrium was conducted. Among these, the Jouyban-Acree-van’t Hoff model yielded the most comprehensive correlation by covering the effects of both temperature and solvent composition variations on the solubility, with a mean relative deviation (MRD%) of 6.4%, suggesting a robust alignment between the modelled and experimental solubility data. Previously trained models were tested to predict the solubility of the drug in mono- and mixed-solvents at various temperatures where accurate predictions were obtained with the MRD% of 19.1% (for mono-solvents), 8.1 and 14.4% (for mixed solvent systems).

Assessing the influence of thermodynamic equation of state and simulation software on modelling the CO2 solubility in physical solvents

The most useful physical solvents in the industry are Propylene Carbonate (Fluor SolventSM), Methanol (Rectisol), Dimethyl Ether of Polyethylene Glycol (DEPG - Selexol) and Sulfolane. To address the challenge of choosing the right software and property package, two commercial software packages, HYSYS 14.0 and ProMax 6.0, are used to model the CO2 solubility experimental data in the above physical solvents at operating pressures and temperatures as this two software are the most applicable software in gas treating simulations. The property packages of Peng-Robinson (PR) and Soave-Redlich-Kwong (SRK) and their regressed versions for CO2 capture purposes by Fluor Corporation and Bryan Research and Engineering LLC are utilized. The results show that the HYSYS Fluor property package demonstrates the strongest agreement with experimental CO2 solubility data in propylene carbonate. In the case of CO2 solubility in methanol, despite HYSYS showing a warning and guiding user to choose Acid Gas property package, HYSYS PR offers a more accurate match below 273.15 K compared with HYSYS Acid Gas and HYSYS Fluor property package and ProMax Polar property packages. ProMax PR and SRK demonstrate a stronger performance in modelling CO2 solubility in sulfolane at all temperatures compared to HYSYS. Both the HYSYS PR and SRK property packages show a high accuracy in modelling CO2 solubility data in DEPG.

Understanding the Impact of Lipids on the Solubilizing Capacity of Human Intestinal Fluids.

Lipids in human intestinal fluids (HIF) form various structures, resulting in phase separation in the form of a lipid fraction and a micellar aqueous fraction. Currently used fed state simulated intestinal fluids (SIF) lack phase separation, highlighting the need for a deeper understanding of the effect of these fractions on intestinal drug solubilization in HIF to improve simulation accuracy. In this study, duodenal fluids aspirated from 21 healthy volunteers in fasted, early fed, and late fed states were used to generate 7 HIF pools for each prandial state. The apparent solubility of seven lipophilic model drugs was measured across these HIF pools, differentiating between the micellar fraction and the total sample (including both micellar and lipid fractions). The solubilizing capacities of these fluids were analyzed in relation to their composition, including total lipids, bile salts, phospholipids, total cholesterol, pH, and total protein. The solubility data generated in this work demonstrated that current fed state SIF effectively predicted the average solubility in the micellar fraction of HIF but failed to discern the considerable variability between HIF pools. Furthermore, the inclusion of a lipid fraction significantly enhanced the solubility of fed state HIF pools, resulting on average in a 13.9-fold increase in solubilizing capacity across the seven model compounds. Although the average composition of the fluids was consistent with previous studies, substantial variability was observed in micellar lipid concentrations, despite relatively stable total lipid concentrations. This variability is critical, as evidenced by the strong correlations between the solubilizing capacity of the micellar fraction and its micellar lipid concentrations. Additionally, this study identified that fluctuations in bile salt concentrations and pH contributed to the observed variability in micellar lipid concentration. In summary, the influence of the lipid fraction on solubility was 2-fold: it enhanced the solubility of lipophilic drugs in the total fluid, and contributed to the variability in the solubilizing capacity of the micellar fraction.

Harnessing Solubility Parameter-based Approaches to Predict Aripiprazole’s Solubility in Solvent Mixtures

Solutions of drugs may behave as ideal solutions, real solutions, or irregular solutions. It is necessary to understand the behaviour of these solutions before attempting to handle them. Various theories/models are reported in the literature to explain their behaviour. The importance of models in predicting the solubility of aripiprazole is demonstrated using its solubility in dioxane-water blends. The method utilizes theoretical and semiempirical approaches to predict solubility. The experimental solubility data for aripiprazole are validated using both ideal and nonideal solutions, focusing on the Scatchard-Hildebrand equation for regular solutions. Furthermore, the Extended Hildebrand Solubility approach is employed to identify the most suitable equation that yields calculated solubility data in agreement with experimental results. Interestingly, a method that directly correlates the solubility parameter of solvent combinations with the logarithm of the mole fraction solubility produces findings comparable to those obtained with the Extended Hildebrand Solubility approach. The results imply that aripiprazole solutions behave as irregular solutions. The solubility profile of aripiprazole may be precisely determined using a quartic equation developed based on regression of activity coefficient versus solubility parameter of the solvent blends. This method saves time and money compared to experimental methods.