Shake-flask Method Research Articles

Correlation of solubility data and solution properties of chlorzoxazone in pure solvents

The accurate determination of solubility of an active pharmaceutical ingredient in a solvent is essential for the design and development of the purification process. The solubility of chlorzoxazone (CHZ) in the pure solvents such as isopropanol, ethyl acetate, 2-ethoxyethyl acetate, and toluene are determined in the temperature range of 278.15 to 333.15 K by shake-flask method at a pressure of 101.2 kPa. The solubility of CHZ in selected solvents is found to increase with temperature. The solubility of CHZ is maximum in 2-ethoxyethyl acetate and minimum in toluene. The mole fraction (x1) solubility of CHZ is correlated with four semi-empirical temperature dependent equations such as the modified Apelblat equation, λh equation, van’t Hoff equation, and non-random two liquid (NRTL) equation. The maximum root-mean-square deviation (RMSD) and relative average deviation (RAD) predicted via four thermodynamic models are 528.80 ×10−4 and 1.146 ×10−2 respectively. The modified Apelblat equation shows a better fit with experimental values for solubility of CHZ. The R2 value obtained from the modified Apelblat equation is >0.99 and the values of RMSD and RAD are smaller for all the selected solvents. The thermodynamic energy properties of the solution are calculated using the van't Hoff equation. The obtained values ΔHm, ΔSm and ΔGm are found to be positive which indicates the dissolution process is an endothermic and entropy-driven process.

Solubility/distribution thermodynamics and permeability of two anthelmintics in biologically relevant solvents

The solubility of mebendazole and flubendazole was measured in aqueous buffers (pH 2.0 and pH 7.4), hexane, and octanol in the temperature range of 293.15–313.15 K by the shake flask method. The molecule ionization state effect on the solubility was investigated. The ionization constants of the compounds at different temperatures were derived from the solubility data. The distribution coefficients in the octanol/buffer (pH 2.0) system at (293.15–313.15 K) and in the hexane/buffer (pH 2.0) system at 298.15 K were measured. The hydrogen bonding potential of the compounds was evaluated using the ΔlogD parameter. The thermodynamic functions of the dissolution and transfer process between the organic and aqueous phases were calculated and discussed. The permeability coefficients through the PermeaPad barrier were determined. The dependences between the distribution and permeability parameters and structural descriptor ΣCad/α were analyzed to obtain the correlation equations.

Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule "Soft" Constraints.

The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published "white paper" (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pH-RSF) method, introduced in our earlier work (Marković et al., 2019), was applied. An improved and more detailed experimental design of the Nor solubility measurement allowed us to exploit the full capacity of the pH-RSF method. Complex equilibria in the aqueous phase (cationic and anionic complex formation between Nor and the phosphate) and solid-phase transformations (Nor free base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts) were characterized by a detailed analysis of the solubility measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth, on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the formulation of drug products.

Nisoldipine in Several Aqueous and Non-Aqueous Cosolvent Solutions: Solubility Modeling and Preferential Solvation Research

The study mainly reported the equilibrated solubilities of nisoldipine in aqueous solutions of n-propanol/acetonitrile + water and non-aqueous solutions of ethyl acetate + ethanol/isopropanol by dint of experimentation and model correlations. Solubility was experimented via the shake-flask method under 101.2 kPa from 278.15 to 318.15 K. The maximum of nisoldipine solubility (in mole fraction unit) was found in neat n-propanol/acetonitrile/ethyl acetate at 318.15 K, and the minimum was found in neat water/isopropanol/ethanol. The total and three-dimensional Hansen solubility parameters were employed herein to explain the solubility behavior of nisoldipine. Modeling solubility through mixture response surface, Jouyban–Acree, and Jouyban–Acree–van’t Hoff models resulted in relative average deviations of <10.3%. Quantitative research upon preferential solvation was carried out by applying the approach of inverse Kirkwood–Buff integrals for the four solution systems considered in the present study and two aqueous solutions of ethanol/isopropanol reported in the literature. The local fractions of n-propanol/acetonitrile/ethanol/isopropanol for the four aqueous solutions as well as ethyl acetate for non-aqueous solution of ethyl acetate + isopropanol were greater than that of bulk ones in n-propanol/acetonitrile/ethanol/isopropanol/ethyl acetate-rich and middle composition proportions, demonstrating that the solvation of nisoldipine was preferred by cosolvents (n-propanol/acetonitrile/ethanol/isopropanol/ethyl acetate). It is able to speculate that nisoldipine displays Lewis acid behavior in these regions with the cosolvent molecules in aqueous solution systems and with the ethyl acetate molecules or isopropanol in the ethyl acetate + isopropanol solution system.

Harnessing the Phytase Production Potential of Soil-Borne Fungi from Wastewater Irrigated Fields Based on Eco-Cultural Optimization under Shake Flask Method

Indigenous fungi present in agricultural soils could have synchronized their inherent potentials to the local climatic conditions. Therefore, the fungi resident in the untreated wastewater irrigated agricultural field might develop their potential for producing various enzymes to handle the induced full organic load from domestic wastewater and toxic chemicals from the textile industry. Around 53 various fungal isolates were grown and separated from the soil samples from these sites through soil dilution, soil-culture plate, and soil-culture plate methods. All the purified fungi were subjected to a phosphatase production test, and only 13 fungal strains were selected as phosphatase producers. Among them, only five fungi identified as Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Penicillium purourogenum, and Mucor rouxii based on morphological similarities, showing higher phosphate solubilizing indices, were utilized for eco-cultural fine-tuning to harness their full production potential under shake flask (SF) method. Among various media, orchestral tuning, 200 µM sodium phytate as substrate with 1.5 mL of inoculum size of the fungi, pH 7, temperature 30 °C, glucose, and ammonium nitrate as carbon and nitrogen additive with seven days of incubation were found to be the most appropriate cultural conditions to harness the phytase production potential of the selected fungi. Aspergillus niger and Aspergillus flavus showed initial phytase activity (5.2 Units/mL, 4.8 Units/mL) and phytase specific activity (2.85, 2.65 Units/mL per mg protein) during screening to be enhanced up to 17 ± 0.033 (Units/mL), 16 ± 0.033 (Units/mL) and (13 ± 0.012), 10 ± 0.066 (Units/mL per mg protein), respectively, with the above-mentioned conditions. The phytase enzyme produced from these fungi were found to be almost stable for a wide range of pH (4–8); temperature (20–60 °C); insensitive to Ca2+ and Mg2+ ions, and EDTA, Ni2+, and Ba2+ inhibitors but highly sensitive to Mn2+, Cu2+, and Zn2+ ions, and Co2+, Cr3+, Al3+, Fe2+ and Ag1+ inhibitors. It was suggested that both phytase-producing strains of A. niger and A. flavus or their crude phytase enzymes might be good candidates for application in soils to release phosphates from phytate and a possible valuable substitute of phosphate fertilizers.

METHOD VALIDATION OF SIMVASTATIN IN PCL-PEG-PCL TRIBLOCK COPOLYMER MICELLES USING UV-VIS SPECTROPHOTOMETRIC FOR SOLUBILITY ENHANCEMENT ASSAY

Objective: This study aims to increase the solubility of simvastatin (SIM), a hydrophobic drug, by incorporating it into PCL-PEG-PCL triblock copolymer micelles and validating the assay method used, namely Uv-Vis spectrophotometric. Methods: The shake flask method was used to determine the increase in solubility experienced by SIM after being incorporated into the micellar system. The values ​​of maximum wavelength (λmax), linearity, LOD, LOQ, accuracy, and precision were used as parameters measured to assess the validity of the assay method used. Results: The results showed that PCL-PEG-PCL triblock copolymer micelles could increase SIM solubility by 9.7 times (89.49±5.75 µg/ml) compared to SIM without modification (9.19±0.24 µg/ml). The validation results show the λmax value of 239 nm, a linear calibration curve with an R-value of 0.9994, LOD and LOQ of 0.33 µg/ml and 1.00 µg/ml, accurate measurement with recovery at concentrations of 80%, 100%, and 120% were 102.93±1.32%, 100.78±0.40%, and 104.58±0.79% and also had good precision ​​with RSD&lt;2%. Conclusion: The PCL-PEG-PCL triblock copolymer micelles can increase SIM solubility and the Uv-Vis spectrophotometric method has been validated successfully for the quantitative analysis of SIM in PCL-PEG-PCL triblock copolymer micelles.

An experimental and theoretical study on the photocatalytic antibacterial activity of boron-doped TiO2 nanoparticles

Boron-doped titanium dioxide nanoparticles (B–TiO2 NPs) were prepared by a sol-gel method. The physicochemical properties of B–TiO2 NPs were characterized by X-ray diffraction, transmission electron microscopy, ultraviolet–visible diffuse reflectance spectroscopy and photoluminescence spectroscopy. The band structure and electrical properties of B–TiO2 NPs were investigated using the first-principle. The effects of the concentration gradient of doping B ions on the photocatalytic antibacterial activity of B–TiO2 NPs under visible-light irradiation were investigated by the inhibition zone method and the shaking flask method. The experimental results show that B–TiO2 NPs are mainly composed of the anatase phase, but no B-related phase was observed. With the increase of the doping amount of boron ions, the particle size decreases and the specific surface area increases. B atoms mainly exist in the form of substitutional dopant and interstitial dopant. Theoretical calculations reveal that B atoms in the TiO2 matrix exist much more easily as interstitial dopant, but B–TiO2 NPs composed of B substituted dopant have better photocatalytic performance. The results of the antibacterial assays show that B–TiO2 NPs have strong antibacterial activities and some bactericidal activities. Finally, the mechanism of the antibacterial activity of B–TiO2 NPs are examined.

Extraction process optimization of flavonoid and in vitro amylase inhibitory effect of purified quercetin derivative from Amorphophallus paeoniifolius tubers

Amorphophallus paeoniifolius (Elephant foot yam) is a prominent tuberous plant utilized across several parts of India to treat various ailments such as a tumour, haemorrhage, microbial infections, cough, bronchitis, diabetes, anaemia, and hepato-gastro and cardiovascular diseases. In this context, the present study aims to optimize the extraction process of the flavonoid and to study the in vitro amylase inhibitory effect of purified flavonoid moiety. The Shake flask method with different extraction solvents was adopted to quantify the flavonoid content. Central composite design (CCD) based response surface methodology (RSM) was formulated to optimize the extraction process. Three-dimensional preparative chromatography (3D PTLC) was executed to purify the flavonoid content and high-resolution liquid chromatography-mass spectrometry (HRLC-MS) was adopted to predict the structure. 3,5-dinitrosalicylic acid (DNS) based spectrophotometry method was used to determine the amylase inhibitory property. All the analyses were subjected to standard statistical tests. The developed model for the extraction optimization process was found to be near significant (P = 0.242) with temperature as a significant variable (P = 0.029), and a 107-fold increase (71.11±0.5 mg/g tissue) of flavonoid content was recorded. A strong yellow colour spot (flavonoid fraction) was eluted using 3D PTLC technique and the molecule was identified as quercetin derivative (m/z 447) by the direct MS method. Significant amylase inhibition (36.1±2.1%) recorded by purified quercetin derivative has documented the utilization of A. paeoniifolius tubers as classical traditional medicine.

Solubility of Nifedipine by Shake Flask UV-Spectrometry; Review of Safety Concerns in Pregnancy

Nifedipine is chemically dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, a dihydropyridine derivative used frequently as anti-hypertensive. It is a L- type calcium channel blocker (CCB). Few analogical discrepancies were found between Nifedipine’s clinical output report and chemical analysis of solubility. The ambition of this research is to conduct a re-check and proper quantification of partition co-efficient (logP) of Nifedipine and clarify the discrepancy and rectify if any mistake has been done in recent past. The method used is the “gold standard” shake-flask method followed by analysis through UV-scpectrophotmetry.

Comprehensive understanding on solubility and solvation performance of curcumin (form I) in aqueous co-solvent blends

The intermolecular interactions and overall charge distribution of curcumin were respectively investigated by using Hirshfeld surface analysis and molecular electrostatic potential surface. The mole fraction solubility magnitudes of curcumin (I) in aprotic co-solvent blends of DMSO + water, acetone + water and acetonitrile + water ranging from 278.15 to 318.15 (333.15) K under 101.1 kPa was obtained by means of shake-flask method. Under the same conditions, e.g. identical temperature and mass fraction of DMSO (acetone or acetonitrile), the equilibrium solubility of curcumin was greater in DMSO + water blends than in acetone/acetonitrile + water blends. The lowest solubility magnitude was found in neat water at 278.15 K; and the highest one, in acetone/acetonitrile at temperature of T = 318.15 K (aqueous solutions of acetone or acetonitrile) or 333.15 K (aqueous solutions of DMSO). No crystaltransition and solvate formation occurred in experimental processes as documented through X-ray power diffraction analysis. The acquired data were correlated by means of the Jouyban-Acree model, Apelblat model and modified van’t Hoff-Jouyban–Acree model. The preferential solvation at 298.15 K was investigated by the approach of inverse Kirkwood–Buff integrals. The parameters of preferential solvation for DMSO, acetone or acetonitrile were positive in the above three blends with middle and DMSO/acetone/acetonitrile-rich composition ranges, which specified that preferential solvation of curcumin was made by co-solvent. The extended Hildebrand solubility approach was further employed to describe the mole fraction solubility at 298.15 K in DMSO/acetone/acetonitrile + water blends studied in the current work and in ethanol/n-propanol/isopropanol/PG + water blends reported previous by us, obtaining average relative deviations < 5.21%.

Synthesis and Characterization of a New Norfloxacin/Resorcinol Cocrystal with Enhanced Solubility and Dissolution Profile.

A new cocrystal of Norfloxacin, a poorly soluble fluoroquinolone antibiotic, has been synthetized by a solvent-mediated transformation experiment in toluene, using resorcinol as a coformer. The new cocrystal exists in both anhydrous and monohydrate forms with the same (1:1) Norfloxacin/resorcinol stoichiometry. The solubility of Norfloxacin and the hydrated cocrystal were determined by the shake-flask method. While Norfloxacin has a solubility of 0.32 ± 0.02 mg/mL, the cocrystal has a solubility of 2.64 ± 0.39 mg/mL, approximately 10-fold higher. The dissolution rate was tested at four biorelevant pH levels of the gastrointestinal tract: 2.0, 4.0, 5.5, and 7.4. In a first set of comparative tests, the dissolution rate of Norfloxacin and the cocrystal was determined separately at each pH value. Both solid forms showed the highest dissolution rate at pH 2.0, where Norfloxacin is totally protonated. Then, the dissolution rate decreases as pH increases. In a second set of experiments, the dissolution of the cocrystal was evaluated by a unique dissolution test, in which the pH dynamically changed from 2.0 to 7.4, stepping 30 min at each of the four biorelevant pH values. Results were quite different in this case, since dissolution at pH 2 affects the behavior of Norfloxacin at the rest of the pH values.

Solubility of baclofen in some neat and mixed solvents at different temperatures

Knowledge of drug solubility is crucial and there is no available cosolvency database for baclofen, so far. In the current study, the solubility and density values of baclofen in five mono-solvents (i.e. methanol, ethanol, 1-propanol, 2-propanol and propylene glycol) and the binary mixed solvents of propylene glycol and ethanol within the temperature range of (293.2 –313.2) K are measured using shake-flask method followed by spectroscopy method. The generated data are correlated using some cosolvency models (e.g. the van’t Hoff, CNIBS/Redlich-Kister, the Jouyban-Acree, the Jouyban-Acree-van’t Hoff and λh models). The mean relative deviations for back-calculated solubility data were employed to investigate the accuracy of the models. Moreover, the apparent thermodynamic properties of dissolution of baclofen in the binary non-aqueous mixtures of solvents such as Gibbs free energy, entropy and enthalpy were computed using van't Hoff and Gibbs equations.

Solubility of amlodipine besylate in binary mixtures of polyethylene glycol 400 + water at various temperatures: Measurement and modelling

Measuring and evaluating of the solubility of amlodipine besylate (AMB), as a low water soluble antihypertensive drug, is fundamentally important in the pharmaceutical industry. In this work, the solubility of AMB in the binary solvent system of water and polyethylene glycol 400 (PEG 400) was determined by a shake-flask method at the temperatures from 293.2 to 313.2 K. According to the obtained results, the solubility of AMB increases nonlinearly with increasing the mass fraction of PEG 400. The maximum mole fraction solubility of AMB was observed at 313.2 K with a PEG 400 mass fraction of 0.9. The experimental solubility data points were correlated by Jouyban-Acree, Jouyban-Acree-van’t Hoff and CNIBS/R-K as linear models and NRTL, Wilson and UNIQUAC as nonlinear models. Of them CNIBS/R-K and NRTL models performed the best in correlation results. The dissolution and mixing thermodynamic properties such as enthalpy, Gibbs free energy, and entropy were also calculated based on Gibbs and van’t Hoff equations to investigate the solvation behavior of AMB in the aqueous PEG 400 mixtures. The density values of AMB saturated mixtures of the PEG 400 and water at different temperatures were also measured and correlated with the Jouyban-Acree model.

QbD-Based Development and Validation of Novel Stability-Indicating Method for the Assay and Dissolution of Garenoxacin in Garenoxacin Tablets.

Garenoxacin mesylate is a novel des-fluoro(6) quinolone, approved and marketed for human use in Japan under the name Geninax. In this current work, a simple and stability-indicating method for the assay and dissolution of garenoxacin in garenoxacin tablets 200 mg was performed. New method developed for the particle size measurement of Garenoxacin mesylate Active Pharmaceutical Ingredient using Malvern 2000. A quality by design (QbD)-based stability-indicating assay method was developed using 0.1% (v/v) formic acid in water and methanol (70:30). Using a photodiode array detector the peak purity of the garenoxacin peak for all degradation samples was studied. The biopharmaceutical classification system (BCS) solubility of garenoxacin mesylate active pharmaceutical ingredient (API) was studied by a modified shake flask method. A dissolution test method was developed using 0.1 N hydrochloric acid as the medium, United State Pharmacopoeia apparatus-II (paddle), revolution per minute (rpm) 50, temperature 37 ± 0.5°C and time 30 min. Liquid paraffin was used as the dispersant in the particle size measurement of garenoxacin mesylate API using the Malvern Mastersizer-wet method. The QbD-based RP-HPLC method was stability-indicating, simple, precise, and accurate. The assay method was linear over 12.5 to 75 µg/mL at the detection wavelength of 280 nm. A UV-based method was developed and validated for the dissolution of garenoxacin 200 mg tablets and the method was found to be linear over 2.9 to 34.2 µg/mL at 280 nm. Based on data, the dissolution tolerance for garenoxacin 200 mg tablets was proposed as Q not less than 80% at time 30 min (% drug released with respect to label claim (Q). The effect of garenoxacin mesylate API particle size in the tablet dosage form was studied using particles of 92 µm and 220 µm [90% of the total particles are smaller than this size (D90)] and it was found that there was no impact on the in vitro dissolution profile. The reported stability-indicating assay and dissolution test methods can be used in regular QC testing of garenoxacin 200 mg tablets. The Malvern particle size wet dispersion measurement method developed and validated for garenoxacin mesylate API is simple and robust. A QbD based RP-HPLC method (using Design Expert Software version 11) was developed and studied peak purity of Garenoxacin peak using Photo Diode Array detector (for all degradation samples, control sample and standard solution) and the same method is validated following USP and ICH guidelines.LC-MS compatible volatile buffer solution is used in the preparation of the mobile phase for the novel stability-indicating RP-HPLC assay method.

Thermodynamic analysis of solubility, distribution and solvation of antifungal miconazole in relevant pharmaceutical media

In this work, solubility of antifungal drug miconazole in pharmaceutically relevant solvents were measured by the shake-flask method in the temperature range between 293.15 and 313.15 K. The solubility of compound in selected solvents increases in the following order: buffer pH 7.4, buffer pH 2.0, hexane, 1-octanol. The influence of protolytic properties of the drug on the solubility in aqueous media of different acidity was studied. It is shown that the modified Apelblat equation give better correlation results with the experimental data than Hoff equation and Two-Suffix Margules model. The Hansen solubility parameters were employed to investigation the miscibility of compound with all of tested solvents. The calculation of the thermodynamic functions of drug solubility and solvation in the selected solvents was performed. The relative contributions of sublimation and solvation to Gibbs energy of solubility for the compound in used solvents was evaluated. The excess Gibbs energy and the activity coefficients of miconazole were also calculated. The temperature dependence of the partition coefficients of the compound studied in the 1-octanol/buffer pH 7.4 system was determined and thermodynamic quantities for the transfer of this drug from water phase to organic one were obtained.

Solubility study of naproxen in the binary mixture of ethanol and ethylene glycol at different temperatures

Solubility and thermodynamic properties of naproxen in the binary mixtures of ethanol and ethylene glycol were determined by shake-flask method followed by a spectrophotometric method in the temperature range of 293.2–33.2.2 K. The acquired solubility values of naproxen are correlated by using some linear and non-linear solubility models such as the van’t Hoff, the MRS, the Jouyban-Acree, the Jouyban-Acree-van’t Hoff, the modified Wilson and the λh models. The accuracy of each used model is tested by the mean relative deviation of the back-calculated data. In addition, density values of saturated mixtures are also determined and represented by the Jouyban-Acree model at defined temperatures. Moreover, the apparent thermodynamic properties of naproxen are calculated based on van't Hoff and Gibbs equations.

Determination of Paclitaxel Solubility and Stability in the Presence of Injectable Excipients

Due to poor aqueous solubility of paclitaxel, cremophor is one of the excipients used to improve solubility in Taxol while it is responsible for a number of adverse effects such as anaphylactic shock. This research was aimed to determine the solubility and stability of paclitaxel in the presence of intravenous injectable excipients. For this purpose, the solubility of paclitaxel was measured in PEG 400, ethanol, miglyol 812, octanoic acid and oleic acid using the shake flask method. Paclitaxel showed the highest solubility in PEG 400 because of possible hydrophobic interaction of the drug with polyethylene chains. The solubility of paclitaxel in ethanol was higher than its aqueous solubility, accentuating the importance of hydrogen bonding. The solubility of paclitaxel was slightly improved in octanoic acid, oleic acid and miglyol 812, presumably for less matching hydrophobic-hydrophilic balance of their molecules with paclitaxel. The stability of paclitaxel was examined in PEG 400, ethanol, and their binary mixture. Paclitaxel exhibited highest stability in the latter case. Probably, this is because of the matching polarity of PEG 400–ethanol mixture with paclitaxel. The effect of anhydrous citric acid on the stability of paclitaxel was also studied. Citric acid significantly improved the stability because it set pH of the prepared compositions in the range of 3 – 5, where paclitaxel exhibited the slowest rate of degradation. The prepared compositions were introduced in aqueous media in various concentrations to study precipitation due to dilution. Precipitation has been observed at all concentrations because paclitaxel is greatly insoluble in water and resists re-dissolving.

Synthesis, characterization, and comparative assessment of antimicrobial properties and cytotoxicity of graphene-, silver-, and zinc-based nanomaterials.

Zinc oxide (ZnO) and graphene oxide (GO) nanoparticles, silver/zinc zeolite (Ag/Zn-Ze), and graphene oxide-silver (GO-Ag) nanocomposites were synthesized and characterized with X-ray powder Diffraction, Field Emission Scanning Electron Microscope and Fourier Transform-Infrared Spectroscopy. The antibacterial efficacy of these nanoparticles was evaluated against E. coli. by shake flask method and plate culture method for different concentrations. For 105 cells/mL initial bacterial concentration, minimum inhibitory concentration (MIC) were<160,<320,<320, and>1280μg/mL, and antibacterial concentration at which 50% cells are inhibited (IC50) were 47, 90, 78, and 250μg/mL for Ag/Zn-Ze, GO, GO-Ag, and ZnO, respectively. Therefore, the shake flask method showed that for all nanoparticle concentrations, Ag/Zn-Ze, and GO-Ag exhibited greater inhibition efficacy, which was also highly dependent on initial bacterial concentration. However, in case of the plate culture method, similar range of inhibition capacity was found for Ag/Zn-Ze, GO-Ag, and ZnO, whereas GO showed lower potency to inhibit E. coli. In addition, GO-Ag nanocomposite exhibited more efficacy than Ag/Zn-Ze when the antibacterial surface was prepared with those. However, Ag/Zn-Ze showed no toxicity on Vero cells, whereas GO-Ag exhibited severe toxicity at higher concentrations. This study establishes GO-Ag and Ag/Zn-Ze as potent antimicrobial agents; however, their application dosage should carefully be chosen based on cytotoxic effects of GO-Ag in case of any possible physiological interaction.

Prediction of n-octanol/water partition coefficient of strongly ionized compounds by ion-pair reversed-phase liquid chromatography with silica-based stationary phase

反相液相色谱(RPLC)是测定正辛醇/水分配系数(log P)的有效方法,但由于缺少同类型模型化合物,RPLC在测定强离解化合物的log P时遇到挑战。该文在硅胶基质C18色谱柱上,采用离子抑制反相液相色谱(IS-RPLC)和离子对反相液相色谱(IP-RPLC)分别对中性化合物、酚酸、羧酸、磺酸及部分两性化合物的保留行为进行了系统研究。在IS-RPLC模式下,利用中性化合物、弱离解的酚酸和苯羧酸作为模型化合物,建立了表观正辛醇/水分配系数(log D)与纯水相保留因子对数值(log kw)的定量结构-保留行为关系(QSRR)模型,测定了19种离解化合物的log D值,作为后续IP-RPLC的模型化合物及验证化合物。在IP-RPLC模式下,将中性、弱离解和强离解化合物作为混合模型组,以溶质静电荷ne、氢键酸碱性参数A和B为桥梁,建立了线性良好的log D-log kw-IP模型,采用3种不同类型的离解化合物进行了外部验证实验,预测值误差低于10%,证实了模型的可靠性。在此基础上,预测了8种强离解化合物的log D7.0值(pH 7.0条件下的log D值)。研究表明,利用结构相关参数沟通不同类型的模型化合物,是实现IP-RPLC测定强离解化合物log D值的一种行之有效的方法。与聚乙烯醇基质色谱柱相比,通用型的硅胶基质色谱柱上尽管存在着更多的次级作用,但可以为强离解化合物log D的测定提供更灵活的选择。

Solubility, solvent effect, enthalpy–entropy compensation and solvation thermodynamics of 4-(bromomethyl)-2(1H)-quinolinone in several aqueous blends

The current study was mainly devoted to solubility for the systems formed by 4-(bromomethyl)-2(1H)-quinolinone (BMQ) and blended solvents of isopropanol, N-methyl-2-pyrrolidinone (NMP), ethanol and n-propanol with water. Experiments for solubility determination were conducted by employing the shake-flask equilibration method from 278.15 to 318.15 K under 101.2 kPa. For each aqueous cosolvent mixture, the minimum solubility was recorded in water at 278.15 K; and the maximum value, in neat organic solvents at 318.15 K. The solubility performance was illustrated by Hansen solubility parameters of water, BMQ and co-solvents. No occurrence of polymorphic transformation or solvation was observed after experiments based on the XRD spectra of raw BMQ and excess solids analyzed. The satisfactory correlation results for solubility data was obtained by modified Wilson model, mixture response surface model, modified van’t Hoff-Jouyban–Acree model and Jouyban–Acree model. The relative average deviations were calculated to be no more than 8.72 %. Investigation on the relative contributions from inter- and intra-molecular interactions to the solubility variation of BMQ at temperature of 298.15 K was quantitatively performed via the linear solvation energy relationships (LSER). The descriptors of solvent blends including solubility parameter, dipolarity-polarizability and hydrogen-bond basicity were primarily responsible for the solubility variation. As well, the preferential solvation of BMQ was researched quantitatively via the inverse Kirkwood–Buff integrals method on the basis of some obtainable properties of solvent blends. The positive preferential solvation parameters for BMQ in middle and cosolvent-rich blends strongly suggest that the crystalline solute of BMQ is preferentially solvated by cosolvents of isopropanol, NMP, ethanol and n-propanol. The transfer and apparent dissolution properties including apparent Gibbs energy change (298.15 K), dissolution enthalpy and dissolution entropy (298.15 K) were derived and discussed. Analysis of enthalpy–entropy compensation indicates the entropy-driven mechanism of BMQ dissolved in all blend solvents.