Solubility Behavior Research Articles

Supercritical CO2 extraction of Walnut (Juglans regia L.) oil: Extraction kinetics and solubility determination

Experimental and modelling investigations of supercritical CO2 extraction of oil from Juglans regia L. kernels were conducted at 200 and 400 bar, 313 and 333 K at a CO2 flow rate of 0.1 kg/h. Regardless of the pressure and the temperature, the highest achievable yield was estimated at about 0.7 kgoil / kgbiomass. The extraction kinetics were modeled with Sovová’s broken and intact cells model. Walnut oil apparent solubility in supercritical CO2 was determined and modelled with the Chrastil equation. A retrograde solubility behaviour was observed at 200 bar, the faster extraction kinetics were found at 400 bar and 333 K. The fatty acid composition of the supercritical CO2 extracted oil was compared to the quality of the oil extracted by press and n-hexane Soxhlet extraction.

Effect of novel surfactant protic ethanolamine based ionic liquids on the aqueous solubility and thermodynamic properties of acetaminophen

The solubility of poorly soluble drugs in aqueous media remains an obstacle in the pharmaceutical development process. Ionic liquids (ILs), with their remarkable solvent properties, have gained considerable attention as potential solubility enhancers for such drugs. In this context, surfactant protic ethanolamine-based ILs have emerged as a particularly promising class of compounds due to their unique dual functionality. This study explores the significant role of these novel solvents in improving drug solubility, focusing on their potential applications in pharmaceutical formulations. Acetaminophen (ACP), a widely used analgesic and antipyretic drug, often encounters solubility limitations that hinder its effective pharmaceutical applications. In the past few years, there has been a growing recognition of the potential of ILs (ionic liquids) as effective solvents. They offer promising prospects for enhancing the solubility of pharmaceutical substances in water-based solutions. This study investigates the enhancement of ACP solubility through the utilization of ILs. The solubilization behavior of ACP in the attendance of mono, bis and tris-(2-hydroxyethylammonium) octanoate systems is explored, highlighting the significant impact of different number of hydroxyethyl groups combinations on its solubility profile. Experimental results reveal that these ILs exhibit a remarkable ability to improve the solubility of ACP, making them attractive candidates for pharmaceutical formulations. The mechanisms underlying this enhancement are discussed, encompassing factors such as the ion-specific interactions, polarity, and hydrogen bonding capabilities of ionic liquids. Furthermore, the potential implications of utilizing ILs for enhancing the bioavailability and formulation versatility of ACP are considered. To accurately correlate the solubility data, various thermodynamic models were employed. Furthermore, to examine the observable thermodynamic characteristics of dissolution in the studied systems Van't Hoff and Gibbs equations were used. The findings indicated that the dissolution process in all co-solvents used was characterized by an endothermic nature and driven by enthalpy.

Structure-bioactivity relationship study on anticancer Pd and Pt complexes with aliphatic glycine derivative ligands

To investigate the structure and bioactivity relationship, six Pd(II)/Pt(II) complexes with N-isobutylglycine (L1) and cyclohexylglycine (L2) as N^O amino acid bidentate ligands, 1,10′-phenanthroline (phen) and 2,2′-bipyridine (bipy) as N^N donor ligands, and [Pd(L1)(bipy)]NO3 (1), [Pd(L2)(bipy)]NO3 (2), [Pd(L1)(phen)]NO3 (3), [Pd(L2)(phen)]NO3·2H2O (4), [Pt(L1)(phen)]NO3 (5), along with [Pt(L2)(phen)]NO3 (6) were prepared and then characterized. The geometry of each compound was validated by doing a DFT calculation. Furthermore, tests were conducted on the complexes’ water solubilities and lipophilicity. All bipy complexes had superior aqueous solubility and less lipophilicity in comparison with phen complexes, as well as complexes containing cyclohexyl-glycine compared to isobutyl-glycine complexes, probably because of the steric effects and polarity of cyclohexylglycine. The in-vitro anticancer activities of these compounds were examined against HCT116, A549, and MCF7 cancerous cell lines. Data revealed that all Pd/Pt complexes demonstrate higher anticancer activity than carboplatin, and complexes 3 and 4 are more cytotoxic than cisplatin against the HCT116 cell line, particularly against MCF7 cancerous cells. In addition, among all compounds, complex 4 has more anticancer ability than oxaliplatin. Due to different solubility and lipophilicity behavior, the accumulation of Pt complexes and clinical Pt drugs in each cancerous cell was investigated. The binding capabilities of these complexes to DNA, as the main target in chemotherapy, occur through minor grooves and intercalate into DNA, which was done using absorption, fluorescence, and circular dichroism spectroscopy. Finally, the docking simulation study showed the mode of DNA bindings is in good agreement with the spectral binding data.

Solubility vs Dissolution in Physiological Bicarbonate Buffer

BackgroundPhosphate buffer is often used as a replacement for the physiological bicarbonate buffer in pharmaceutical dissolution testing, although there are some discrepancies in their properties making it complicated to extrapolate dissolution results in phosphate to the in vivo situation. This study aims to characterize these discrepancies regarding solubility and dissolution behavior of ionizable compounds.MethodsThe dissolution of an ibuprofen powder with a known particle size distribution was simulated in silico and verified experimentally in vitro at two different doses and in two different buffers (5 mM pH 6.8 bicarbonate and phosphate).ResultsThe results showed that there is a solubility vs. dissolution mismatch in the two buffers. This was accurately predicted by the in-house simulations based on the reversible non-equilibrium (RNE) and the Mooney models.ConclusionsThe results can be explained by the existence of a relatively large gap between the initial surface pH of the drug and the bulk pH at saturation in bicarbonate but not in phosphate, which is caused by not all the interfacial reactions reaching equilibrium in bicarbonate prior to bulk saturation. This means that slurry pH measurements, while providing surface pH estimates for buffers like phosphate, are poor indicators of surface pH in the intestinal bicarbonate buffer. In addition, it showcases the importance of accounting for the H2CO3-CO2 interconversion kinetics to achieve good predictions of intestinal drug dissolution.

Characterizations and solubility profile of novel senary SiO2–CaO–Na2O–P2O5–CaF2–SrO glass structure modified with Nb2O5

The solubility/degradability of bioactive glasses play crucial role in bone tissue engineering applications owing to the release of ions from their structure, which exert therapeutic effects on tissues. The present study evaluates the findings of a detailed investigation on the main features and solubility behaviors of newly formulated Nb incorporated glasses (Nb-BGs). New glass formulation in SiO2–CaO–Na2O–P2O5–CaF2–SrO–xNb2O5 (x: 0.0, 0.5, 1.0, and 1.5 mol. %) system was successfully synthesized by melt-quenching technique. Glass composition was verified with Energy Dispersive X-ray Fluorescence spectrometer analysis and its amorphous nature, functional groups of the matrix and morphological features were identified via X-Ray diffraction analyses, Fourier Transform Infrared Spectroscopy and Scanning Electron Microscope analysis, respectively. Network connectivity (NC) of the Nb-BGs was assessed with respect to the role of Nb2O5 in the glass matrix as network former, modifier, or both. In order to evaluate the in vitro solubility of Nb-BGs, released concentrations of particular ions from the glass compositions were determined at certain time points and comprehensively discussed with several mathematical models such as zero-order, first-order, second-order, Higuchi, and Korsmeyer-Peppas for the first time. Results showed that the incorporation of Nb2O5 (up to 1.5 mol. %) increased the density, oxygen density as well as NC values of newly formulated glasses. Si, Na and Ca ions which play a main role in well-defined Hench's mechanism followed mostly second-order release kinetics for all glasses in the mathematical models studied. When the Nb content increase (to 1.5 mol. %) in glass composition, the release mechanism of Si ion according to Korsmeyer-Peppas model shifts from the diffusion mechanism to an erosion-dominant release mechanism.

Solubilization study of antihypertensive drug Irbesartan in EO-PO based polymeric nanomicelle and optimization of its release behavior

Irbesartan (IRB) has low bioavailability due to its poor aqueous solubility and dissolution rate, thereby making it imperative to understand their absorption behavior. The present research work is aimed for improvement of solubilization of IRB, by investigating the effect of molecular characteristics/hydrophobicity of Pluronic® copolymers; P84 and F108 micelles with and without added salt (NaCl). The solubility of IRB was increased with copolymer concentration. Effect of added salt (NaCl) showed completely opposite behavior for both the copolymers; where F108 with NaCl has adverse effect on IRB solubilization and considerable decrease was observed. The micelle/water partition coefficient and the standard free energy change (∆G◦) were also evaluated from thermodynamic view point. The in vitro release kinetics of IRB drug was carried out for 1% P84 with and without 1 M NaCl and compared with its release in water. It was found that P84/NaCl reduces the release rate more efficiently for IRB compared to other systems. There are few reports about the solubilization improvement of IRB; but this is the first time where the study of Pluronic® micelle carried out for IRB solubilization with varying solvent condition as per best of our knowledge. This information can be useful to understand the solubilization behaviour of Pluronic® copolymers available in varieties of molecular weights and can be used to identify possible solvent condition for newer applications of Pluronic® copolymers in pharmaceutical field.

Insight into the solution thermodynamic properties of cimetidine form A and form B based on experiments and molecular simulations

Cimetidine (CIM) is an antagonist of the type II histamine receptors, and act as a significant agent in the treatment of stomach ulcers. In this work, the effect of polymorphism and solvent type on the thermodynamic properties of CIM was investigated based on experimental results and molecular simulations. The solubility data of two polymorphs for CIM (forms A and B) in organic solvents were measured and correlated with four thermodynamic models. It could be found that the solubility of CIM form A is higher compared to form B. In addition, molecular simulations were adopted to investigate the mechanism of the solubility and stability of the two forms. Hirshfeld surface analysis shows that strong H···N interaction contributes to better stability of form B. Meanwhile, molecular electrostatic potential surface and radial distribution function results indicate that the solubility behavior is significantly influenced by the intensity of the solute–solvent interactions. Finally, the dissolution thermodynamic properties, including the enthalpy change, the Gibbs energy change, and the entropy change, were calculated and the results show that the dissolution process of CIM is endothermic, entropy-driven and spontaneous.

A novel simulated media system for in vitro evaluation of bioequivalent intestinal drug solubility

Orally administered solid drug must dissolve in the gastrointestinal tract before absorption to provide a systemic response. Intestinal solubility is therefore crucial but difficult to measure since human intestinal fluid (HIF) is challenging to obtain, varies between fasted (Fa) and fed (Fe) states and exhibits inter and intra subject variability. A single simulated intestinal fluid (SIF) cannot reflect HIF variability, therefore current approaches are not optimal. In this study we have compared literature Fa/FeHIF drug solubilities to values measured in a novel in vitro simulated nine media system for either the fasted (Fa9SIF) or fed (Fe9SIF) state. The manuscript contains 129 literature sampled human intestinal fluid equilibrium solubility values and 387 simulated intestinal fluid equilibrium solubility values. Statistical comparison does not detect a difference (Fa/Fe9SIF vs Fa/FeHIF), a novel solubility correlation window enclosed 95% of an additional literature Fa/FeHIF data set and solubility behaviour is consistent with previous physicochemical studies. The Fa/Fe9SIF system therefore represents a novel in vitro methodology for bioequivalent intestinal solubility determination. Combined with intestinal permeability this provides an improved, population based, biopharmaceutical assessment that guides formulation development and indicates the presence of food based solubility effects. This transforms predictive ability during drug discovery and development and may represent a methodology applicable to other multicomponent fluids where no single component is responsible for performance.

Sequence-dependent dipeptide solubility in ethanol-water and DMSO-water solutions

Reliable solubility data is crucial for controlling and optimising crystallisation conditions, to provide a cost-effective purification method with the potential for scaling up. This study investigated the effect of amino acid sequence on determining peptides solubility behaviours. Four dipeptides with different sequences and combinations of alanine and glycine were selected to study their temperature dependent (283.15 K to 313.15 K) aqueous solubilities and solubility in the presence of ethanol and DMSO as antisolvent at 298.15 K. Aqueous solubility data of dipeptides presents the following order: glycyl-L-alanine (gly-ala) > L-alanyl-L-alanine (ala-ala) > glycyl glycine (gly-gly) > L-alanyl glycine (ala-gly). This solubility order has been substantiated by solvation free energy calculations using molecular dynamics (MD) simulations, providing insights into the underlying molecular interactions that govern these solubility patterns. The solubility data also demonstrated difference in the temperature dependency that: gly-gly > gly-ala > ala-gly > ala-ala, corresponding to their dissolution enthalpy order. In the presence of antisolvent range from 0 % to 80 % (by mass) concentration, peptide’s solubility was more susceptible to DMSO than ethanol. Accurate prediction of the solubilities validated the effectiveness of non-random two-liquid (NRTL) model for peptide studies.

Solid-liquid equilibrium of forchlorfenuron in four binary solvents: Experiments, hansen solubility parameter and molecular simulation

In this research, the solubility of forchlorfenuron in 4 binary solvent systems {(methanol, ethanol, n-propanol and acetone) + water} was determined at certain experimental conditions (pressure of 101.3 kPa, temperature of 278.15 K-323.15 K) using laser dynamic monitoring method. Five thermodynamic models were applied to correlate and analyze the experimentally measured data. The modified Apelblat model has the lowest value of ARD (100ARD = 2.046 %) indicates that it fits best. The apparent thermodynamic properties during the dissolution process of forchlorfenuron in the four mixed solvent systems were explored using Van't Hoff equation. The effect of solvent properties on the dissolution was explored by calculating Hansen solubility parameters. For further understanding the solubility behavior on the molecular scale, molecular electrostatic potential analysis and Hirshfeld surface analysis were conducted to visualize the molecular surface charge distribution and predict the contact behavior between forchlorfenuron and solvent. Finally, the influence of intermolecular interactions between solute and solvent on solubility behavior was explored using radial distribution function analysis based on molecular dynamics simulations. And the results show the stronger intermolecular force corresponds to the larger solubility.

Solubility Behavior of α-Aminoisobutyric Acid in 13 Individual Solvents at Temperatures Ranging from 283.15 to 323.15 K

Solubility Behavior of α-Aminoisobutyric Acid in 13 Individual Solvents at Temperatures Ranging from 283.15 to 323.15 K

Solubility behavior and thermodynamic properties of caprolactam in four pure solvents and two cosolvent mixtures

The purpose of this work is to study the dissolution behavior of caprolactam in different solvents and to provide solid-liquid equilibrium data for the design and operation of crystallization and purification process for production and recovery of caprolactam. The mole fraction solubility of caprolactam was investigated in four pure solvents (benzene, ethyl acetate, cyclohexane, acetonitrile) and two cosolvent mixtures (ethyl acetate + cyclohexane, benzene + cyclohexane) by gravimetric method at atmospheric pressure from 277.65 K to 323.65 K. At the same temperature, the order of solubility of caprolactam in the selected pure solvents is: benzene > acetonitrile > ethyl acetate > cyclohexane. In the selected cosolvent mixtures, the solubility increases with increasing temperature and the content of good solvent. A series of thermodynamic models were used to fit the experimental solubility data. Finally, the thermodynamic properties of caprolactam in selected solvents were studied using the van't Hoff equation. From this analysis, it was concluded that the dissolution of caprolactam in the selected solvents is a heat-absorbing and entropy-increasing process.

Micellization, aggregation, interaction, and solubilization behaviors of mixed solutions of cationic gemini and nonionic surfactants

AbstractThe micellization properties of mixed aqueous solutions of a cationic gemini surfactant (CGS) and Triton X‐100, a conventional non‐ionic surfactant, with various mole fractions, were determined by measuring the surface tension at different temperatures. Various theoretical models were used to analyze the behavior of this mixed system. The interactions between CGS and Triton X‐100 were determined to be non‐ideal and synergistic. The calculated interaction parameters (βM) have negative values at all temperatures and for all mole fractions, showing attractive interactions. It was found that increasing the mole fraction of Triton X‐100 significantly increased the synergistic effect (more negative values). Micellar aggregation number (Nagg) values of pure surfactants and their mixtures in different ratios were obtained with the steady‐state fluorescence quenching method. Furthermore, the molar solubilization ratio of Sudan III organic dye in all surfactants aqueous systems was obtained using UV–Visible spectrophotometry. At concentrations above critical micelle concentration, the solubility of Sudan III in water was substantially increased linearly for all systems and it was observed that the enhancement was even more significant for mixed surfactant systems.

A Retrospective Analysis of Polymer Selection Using Solvent Casting: Formulation and DoE Optimization of the Amorphous Solid Dispersion of Amoxicillin Trihydrate by a Spray Drying Method

Background. Amoxicillin trihydrate possesses poor solubility, compressibility, and flow behavior. Amorphous solid dispersion prepared by spray drying could solve all three problems at the same time. Objective. To prepare amorphous solid dispersion after screening of polymers by solvent casting method using a spray drying method. Methods. The solvent casting method was used to screen polymers, PVP/VA S-630, PVP K30, Soluplus, PEG 4000, HPMC AS, and HPMC HP55, in 1 : 1 and 2 : 3 ratios and followed by spray drying after polymer selection. Results. The dissolution performance of the formulation improved with time. The optimum feed rate and feed concentration were found to have an impact on the flow properties and particle size of spray-dried formulations, and they were selected as independent variables in a 32 full factorial statistical design. The ANOVA and regression analysis suggest that the developed regression model has a significant overall fit to the data and can explain a substantial proportion of the variability in the dissolution at 10 minutes. The optimized batch was selected based on the decisive factors of minimum and maximum values of response variables. Overall, the optimized batch demonstrated improved characteristics in terms of percentage yield (32.81%), dissolution at 10 min (49.70%), and angle of repose at 31.42°. Conclusion. This study provides valuable insights into optimizing formulation strategies for preserving the amorphous state of drugs and contributes to the development of stable pharmaceutical formulations.

Employment of artificial intelligence approach for optimizing the solubility of drug in the supercritical CO2 system

This paper investigates the solubility behavior of digitoxin in supercritical carbon dioxide (CO2) through a comprehensive analysis employing ensemble learning techniques and various regression models. The dataset consists of temperature and pressure as input variables, with solvent density and digitoxin solubility as output variables. Utilizing bagging as the ensemble method, Gaussian process regression (GPR), Bayesian Ridge Regression (BRR), Orthogonal Matching Pursuit (OMP), and Polynomial Regression (PR) were employed as regression models. Hyper-parameter tuning was achieved through gradient-based optimization. Results revealed that Polynomial Regression (PR) emerges as the most effective model for predicting both solvent density and digitoxin solubility. For solubility prediction, BAG-PR yields an R2 score of 0.98527, with MSE and MAE of 1.4290E-03 and 3.40547E-02, respectively. Concerning solvent density, BAG-PR achieves an outstanding R2 of 0.99766, along with MSE and MAE of 7.4759E+01 and 7.33964E+00, respectively. These results show that ensemble learning, and polynomial regression can accurately predict solubility and solvent density, revealing digitoxin's behavior in supercritical CO2.

Polymorphs of praziquantel–succinic acid cocrystal: Crystal structure, thermodynamic relationship, and improved pharmaceutical performance

Polymorphism is a ubiquitous phenomenon of critical significance for the pharmaceutical industry, yet reports on cocrystal polymorphs are scarce. This study elucidates the crystal structure of the praziquantel (PZQ)-succinic acid (SUC) cocrystal polymorph, α-PZQ-SUC. The dominant supramolecular interaction in the cocrystal polymorph is the O − H···O hydrogen bond between SUC and PZQ, consistent with the supramolecular interaction in the previously reported β-PZQ-SUC polymorph. Comprehensive analysis, including thermal analysis, theoretical calculations, and solvent-mediated polymorphic transformation experiments, established a monotropic relationship between the two polymorphs, with α-PZQ-SUC demonstrating greater stability than β-PZQ-SUC. Both α-PZQ-SUC and β-PZQ-SUC enhance the solubility and dissolution behavior of PZQ, indicating their suitability for pharmaceutical applications based on improved pharmaceutical performance.

Preparation, characterization and in vitro digestion of jujube polysaccharide microcapsules

The preparation of jujube polysaccharide microcapsules was investigated in this study. Microcapsule technology was employed to encapsulate jujube polysaccharides, effectively isolating them from external substances and facilitating their smooth passage through the intestinal tract. The objective was to control the release and prolong the release time of the polysaccharides. Additionally, we evaluated the characteristics of these microcapsules and their in vitro solubility and digestive behaviors. The findings demonstrated that the optimal preparation conditions, measured by the encapsulation efficiency, included a sodium alginate concentration of 4% (w/v), a core-to-wall ratio of 1:6, a calcium chloride concentration of 3% (w/v), and a chitosan concentration of 0.5% (w/v). The factors influencing the process ranked in the following order: core-to-wall ratio > sodium alginate concentration > chitosan concentration > CaCl2 concentration. The microcapsules produced under the optimal conditions exhibited a remarkable encapsulation efficiency of 97.29%. The characterization and analysis of the jujube polysaccharide microcapsules confirmed their successful encapsulation, uniform particle size distribution, and robust thermal stability. In addition, swelling and in vitro release trials demonstrated that the jujube polysaccharide microcapsules exhibit excellent swelling characteristics and consistent and prolonged release patterns. These distinct characteristics are anticipated to significantly impact functional food and medicine.

Hydroxyl-terminated triazine dendrimers mediated pH-dependent solubility enhancement of glipizide across dendritic generations: A comparative investigation

A huge challenge for the pharmaceutical industry is hydrophobic compounds, which affect aqueous solubility, an important measure of a medicine’s efficacy. Several approaches have been used; dendrimers are particularly noteworthy because of their long-term viability, nanoscale size, large payload capacity, and adaptable end functional groups. The unique architecture of dendrimers allows for modified medication delivery and solubility profiles, making them a powerful tool for improving the solubility of hydrophobic drugs. This marks the beginning of a new era in pharmaceutical formulations. A new era in drug formulations has begun with this. As part of this study, we synthesized third-generation hydroxyl-terminated triazine-based dendrimers by meticulously reducing chlorine groups following Michael’s addition. We intend to methodically examine the effects of various concentrations of these dendrimers on the solubility behavior of glipizide, a pharmaceutical agent with intrinsic hydrophobicity, across the first, second, and third generations (the full generation). A stimulating tale of solubility improvement emerged from our research. Glipizide’s solubility was positively correlated with the concentration and generational progression of the dendrimers. The solubility of hydrophobic drugs in water can be dramatically altered by dendrimers based on hydroxyl-terminated triazine. This field of study benefits from adding new dendrimers with each generation.

Curcumin@Fe/Tannic Acid Complex Nanoparticles for Inflammatory Bowel Disease Treatment.

Inflammatory bowel disease (IBD) is a serious public health issue because of its chronic and incurable nature. Common IBD drugs have limited efficacy and produce adverse effects, leading to an urgent need to develop new drugs and drug delivery systems. Curcumin (Cur) is a natural and nontoxic drug that is increasingly used in the treatment of IBD owing to its anti-inflammatory and antioxidant effects. Metal-polyphenol networks constructed from metal ions and polyphenols exhibit biological functionality while acting as an adhesive nanomaterial to encapsulate nano-Cur, thereby improving its solubility and drug release behavior. In this study, we prepared a Cur@Fe&TA nanodrug delivery system by constructing an Fe3+/tannic acid (TA) metal-polyphenol network with encapsulated Cur. The Cur@Fe&TA nanodrug exhibited good stability, drug release behavior, and biocompatibility. Based on the anti-inflammatory and antioxidant effects of Cur@Fe&TA, the gastrointestinal cytopathology in an IBD mouse model was effectively improved. The proposed Cur@Fe&TA nanomedicine delivery system has promising application and research value for the treatment of IBD by regulating levels of antioxidants and inflammatory cytokines.

Novel and effective peripheral tetra-substituted phthalocyanines with quinazoline groups for cancer treatment: synthesis, photophysical and photochemical properties, and in-vitro studies

Within the scope of this study, starting from 3,4-dihydronaphthalen-1(2H)-one (1), 4-(2-amino-5,6-dihydrobenzo[h]quinazolin-4-yl)phenol (3) was synthesized in two stages according to literature. In the second step, 4-(4-(2-amino-5,6-dihydrobenzo[h]quinazolin-4-yl)phenoxy)phthalonitrile (4) was prepared as the starting ligand compound with the help of this substance for the first time. Then, novel metallophthalocyanine derivatives [2(3), 9(10), 16(17), 23(24)-Tetrakis[4-(2-amino-5,6-dihydrobenzo[h]quinazolin-4-yl)phenol] phthalocyaninato zinc(II) (5), copper (II) (6), cobalt (II) (7)] were synthesized in the presence of suitable metal salts. The structure of synthesized procersur and novel compounds were elucidated by convenient spectroscopic methods. The effect on solubility and aggregation behaviors substitution with 4-(2-amino-5,6-dihydrobenzo[h]quinazolin-4-yl)phenol from the peripheral position was investigated. The newly synthesized tetra-substituted phthalocyanines (5–7) show good solubility in common organic solvents. Also, they have no aggregation tendency between 1 and 10 µM concentrations. In addition, the photophysical and photochemical properties of substituted phthalocyanines were examined. The ability to produce 1O2 of compound (5) was 0.79 in DMSO and 0.75 in THF media. Finally, the cytotoxicity effects of the synthesized phthalonitrile (4) and its metallophthalocyanines (5–7) on MCF 7, MDA-MB-231, HT-29, C6, AGS and L-929 cells were determined by XTT (2,3bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazolium hydroxide) method. The obtained data were compared with standard cell lines.