Niclosamide & challenges in chemical modifications: A broad review on enhancement of solubility

Niclosamide is classified under World Health Organization's crucial medicines and it is categorized as an anthelmintic drug to target tapeworm infections. In recent findings it is successfully repurposed as a multifunctional drug effective against many diseases. The approach for synthesis of niclosamide is very crisp, simple and affordable. Besides these outstanding activities and easy method of synthesis, the poor solubility which down regulate the bioavailability of niclosamide has prevented its advance development for clinical therapy. This article reviews various methods studied by vast researchers to enhance the solubility which lead to increased efficacy and potential in targeting the diseases. The review also focuses on the application of niclosamide derivatives in different therapeutic uses which proves its broad and vast activity to treat many diseases. The experimental studies to enhance the solubility using chemistry approaches are progressing to achieve the success in developing niclosamide based therapies and broaden its applications.“The experimental study to enhance the solubility by chemistry aspect is progressing continuously to achieve the success in its uses. “Therefore, in present review we have broadly discuss the challenges, synthesis, chemical modification for solubility enhancement and application of niclosamide as gold drug in clinical field”.     

Effect of Hydrogen Bonding on Cellulose Solubility in Aqueous and Nonaqueous Solvents

Interrelation between the hydrogen bonding energy in cellulose, its solubility in aqueous and nonaqueous solvents is examined. Factors controlling the solubility and selection criteria for nonaqueous solvents for cellulose are analyzed.     

Dependence of the solubility of atmospheric oxygen in weakly alkaline aqueous solutions on surfactant concentration

The solubility of atmospheric oxygen in solutions of surfactants of different natures at 293 K and pH 8 is determined by gas chromatography. It is found that additives of nonionic surfactants decrease the oxygen content in the solution in the premicellar region and increase its solubility in the micellar region. It is shown that, for anionic surfactants, a decrease in the solubility of O₂ is observed over the entire concentration range.     

Revisiting the Solubility Concept of Pharmaceutical Compounds

Summary.  The kinetic and thermodynamic solubilities of Roche (Ro) pharmaceutical compounds were determined by HPLC, titrimetry, and UV/Vis spectroscopy in aqueous buffers and in non-buffered systems. For kinetic solubility, a turbidimetric method that allows the rapid determination of solubilities using small amounts of compounds (5–50 mg) was used. Two types of precipitation were observed during the kinetic solubility determinations: i) a disperse precipitation where the solution became foggy with very small particles uniformly distributed in the solution, and ii) discrete precipitation characterized by formation of crystals that rapidly sediment. The thermodynamic solubility was determined by shake flask and titrimetrically using a pH-STAT. The pH-STAT titrimetric method for the pH-thermodynamic solubility profile determination eliminates the buffer species and represents a new way to approach the solubility characterization of pharmaceutical compounds. The strengths of the turbidimetric method for determining the kinetic solubility are its rapidity, minimal compound requirements, and suitability for high throughput screening. The limitations are that the maximum solubility is limited to less than 100 mg · cm⁻³, and the precipitation of trace impurities cannot be distinguished from precipitation of the analyte. The pH-STAT titrimetric approach for the thermodynamic solubility has a lower throughput and is suitable for the characterization of the lead candidate. It is not limited in its solubility range and provides a common basis for the comparison of the solubility values at different pH values in contrast to traditional buffered systems. Received August 21, 2000. Accepted (revised) February 5, 2001     

Dissolution Enhancement and Characterization of Nimodipine Solid Dispersions with Poloxamer 407 or PEG 6000

The solid dispersion approach is an alternative to increase drug solubility. Many carriers have been studied, but there is few information about poloxamer 407 (P407). Consequently, the objective of this study was to evaluate P407 as a carrier for nimodipine solid dispersions and to compare its solubility and dissolution rates with those from polyethylene glycol (PEG 6000). The solid dispersions were prepared by the hot melting and solvent methods and they were characterized by FTIR, DSC, solubility, and dissolution tests. The results indicated a three-fold increase in solid dispersions solubility in the presence with P407 than those prepared with PEG.     

Solubility Parameter of Gatifloxacin and Its Correlation with Antibacterial Activity

The solubility parameter of gatifloxacin was calculated theoretically by Fedors’ method and also determined experimentally using the standard solubility method. The molar volume of gatifloxacin was determined experimentally by the flotation method. Three solvents, ethyl acetate, propylene glycol and water were used to prepare nine binary mixtures having different solubility parameter values varying from 8.9 to 23.4 H. The δ ₂ solubility parameter of gatifloxacin was found to be 12.4 H. The cumulative transport of gatifloxacin from the binary solvent mixtures (ethyl acetate–propylene glycol and propylene glycol–water) exhibited an inverse parabolic relationship to the solubility parameter of the solvent mixtures. Transport studies revealed that the extent of gatifloxacin rejection from solvent mixtures was dependent on its solubility parameter and system composition. In the selected organisms (bacteria), a minimum zone of inhibition was observed in a solvent mixture having the solubility parameter nearest to the solubility parameter of gatifloxacin. Two models were employed for the evaluation of the antibacterial activity of gatifloxacin in binary mixtures.     

Influence of Properties of Nonaqueous Solvents on the Solubility of NH<Subscript>4</Subscript>Cl and Thermodynamics of Its Solution

The solubility of ammonium chloride in acetonitrile, dioxane, and 2-propanol in the range 298.15–338.15 K was determined using ³⁶Cl tracer. The influence of properties of nonaqueous solvents on the solubility of ammonium, potassium, and sodium chlorides was subjected to thermodynamic and correlation analysis. The low solubility of ammonium chloride in dioxane and acetonitrile is due to the endothermic effect, and its high solubility in 2-propanol, to the exothermic effect of the salt solution. The entropy of solution affects the solubility of ammonium chloride in acetonitrile only slightly, in contrast to dioxane and 2-propanol in which the entropies of solution are significant and have opposite signs. The solubility of ammonium and potassium chlorides depends on the electron-acceptor power of the solvents and electrostatic interactions in solution, whereas the solubility of sodium chloride in organic solvents is determined by the combined influence of the donor-acceptor and dielectric properties of the solvents.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 1, 2005, pp. 29–35.Original Russian Text Copyright © 2005 by Zaitseva, Sytnik, Krasnoperova, Bondarev.     

Feasibility of on-line supercritical fluid extraction of steroids from aqueous-based matrices with analysis via gas chromatography-mass spectrometry

The solubility of testosterone, boldenone, androstenone, etiocholanolone, and epitestosterone are measured in pure supercritical CO2. Testosterone exhibited the highest solubility in supercritical CO2. The solubility of all steroids except epitestosterone increased by one order of magnitude with increasing pressure from 100 to 400 atm. Epitestosterone had the lowest solubility in supercritical CO2 and its solubility was not affected by pressure. The extraction efficiency of steroids from an aqueous saline environment exceeded 95%. Because of the partial solubility of water in supercritical CO2, the addition of a moisture trap after the aqueous vessel is necessary to prevent the plugging and deterioration of the gas chromatographic (GC) column. It is demonstrated that on-line supercritical fluid extraction-GC-mass spectrometry is feasible for the quantitative extraction and analysis of steroids from both saline and urine solutions. However, it is determined that the adsorbent vessel filled with Hydromatrix is not sufficient to trap all the moisture, and after 3 to 4 extractions, the GC column efficiency lowered.     

Solubilization of organic compounds by arginine-derived polymers

Poor aqueous solubility of drugs is one of the major challenges in the pharmaceutical science. In this study, a guanidinium-containing polymer based on arginine was designed and synthesized, and was evaluated as a solubility enhancing additive for three model organic compounds (coumarin, pyrene and doxorubicin). At a guanidinium group concentration of 100 mmol/L, the polymer could significantly increase the solubility of pyrene and doxorubicin by 6-and 11-fold respectively, much more effective than arginine (2-and 3-fold, respectively). In contrast, its effect on the solubility of coumarin was less effective than arginine. The solubilizing effect may be explained by the enhanced interaction between the guanidinium group in the polymer and the aromatic compounds.     

超临界CO2在聚合物中的溶解计算研究进展

本文以超临界CO2在聚合物中的溶解计算模型为例,综述了状态方程、经验方程和人工神经网络计算方法的实现原理、研究现状和优缺点;依据人工神经网络预测方法存在的问题,重点阐述基于混合智能方法的神经网络溶解计算模型;并对溶解计算研究进行了总结和展望。     

Estimation of aqueous solubility in drug design

The solubility of drugs in water is of central importance in the process of drug discovery and development from molecular design to pharmaceutical formulation and biopharmacy. The ability to estimate the aqueous solubility and other properties of a promising lead compound affecting its pharmacokinetics is a prerequisite to rational drug design, although it has received much less attention than the prediction of drug-receptor interactions. In this review, methods for the estimation of aqueous solubility of organic compounds are described and limited to approaches, which might be used in the early stage of drug design and development.     

相溶解度法研究芦荟大黄素和环糊精及其衍生物的包结作用

本文用相溶解度法研究了芦荟大黄素与β－环糊精（ＣＤ）衍生物的包结作用,测定了包结物的包结常数,表明β－ＣＤ衍生物对芦蔡大黄素有较好的增溶作用,有应用价值。     

那格列奈的多晶型与溶解度

分别对那格列奈B, H和S三种晶型的溶解度、溶解热进行了测定和计算. 结果表明: 那格列奈的S晶型与临床使用的H晶型溶解度均明显大于B晶型. B, H和S三种晶型的溶解热分别为42.84, 28.44 和29.14 kJ•mol^－1. 此外, 我们还新发现了不同于B, H, S晶型的X2晶型, 并且制备出了无定型的那格列奈.     

Oxidation of hydrolysis lignin with hydrogen peroxide in acid solutions

Optimal conditions were determined for oxidation of hydrolysis lignin and other insoluble lignin samples with hydrogen peroxide in acid solutions, ensuring solubility of lignin in dilute alkali. The correlation was found between the functionalization and solubility of hydrolysis lignin and its oxidation products. A procedure was suggested for determining carboxy groups in lignin.     

Development of machine learning model and analysis study of drug solubility in supercritical solvent for green technology development

The current research is focused on development of machine learning model for estimation of pharmaceutical solubility in supercritical CO₂ as the green solvent. The main aim is to assess the suitability of supercritical processing for preparation of nanomedicine. Oxaprozin was taken as model drug for the solubility measurements, and its solubility was determined at different operational conditions by variation of temperature and pressure of the process. Artificial Neural Network (ANN) model was implemented for simulation of the drug solubility, and the best model was obtained with R² greater than 0.99 for the training and validation as well. The tested model was then exploited to understand the process, and it turned out that both pressure and temperature had major and considerable influence on the solubility of Oxaprozin in supercritical carbon dioxide as solvent. However, the effect of pressure was shown to be more significant on the solubility compared to the effect of pressure, which was attributed to the effect of pressure on the density of the supercritical solvent. The developed ANN model was indicated to be robust in estimating the values of drug solubility in wide range of conditions which can save time and cost of the measurements.     

壳聚糖及其衍生物抗菌活性的研究进展

壳聚糖是自然界目前发现的唯一碱性多糖,具有自然来源丰富,生物相容性好,可被生物降解,安全无毒和抗菌性强等许多天然的优良特性,现其广谱抗菌性已得到广泛的认可,但较差的水溶性限制了它的进一步应用。因此,通过一定的改性方法制备壳聚糖衍生物以提高其水溶性,是目前壳聚糖研究方面的热点之一。本论文就近年来几种常见的壳聚糖亲水改性方法及其衍生物在抗菌方面的应用进展进行综述,以期对壳聚糖的深入研究提供参考。     

Analysis of the phase solubility diagram of a phenacetin/competitor/beta-cyclodextrin ternary system, involving competitive inclusion complexation

The competitive inclusion complexations in the ternary phenacetin/competitors/beta-cyclodextrin (beta-CyD) systems were investigated by the solubility method, where m-bromobenzoic acid (m-BBA) and o-toluic acid (o-TA) were used as competitors. The solubility changes of the drug and competitors as a function of beta-CyD concentration in the ternary systems were formulated using their stability constants and intrinsic solubilities. The decrease in solubility of phenacetin by the addition of competitors could be quantitatively simulated by the formulation, when both drug and competitor give A(L) type solubility diagrams. On the other hand, when one of the guests gives a B(S) type solubility diagram, its solubility change was clearly reflected in that of the another guest, i.e., phenacetin gave an A(L) type solubility diagram in the binary phenacetin/beta-CyD system and o-TA gave a B(S) type diagram in the binary o-TA/beta-CyD system, but in the ternary phenacetin/o-TA/beta-CyD system, a new plateau region appeared in the original A(L) type diagram of phenacetin. This was explained by the solubilization theory of Higuchi and Connors. The solubility analysis of the ternary drug/competitor/CyD systems may be particularly useful for determination of the stability constant of a drug whose physicochemical and spectroscopic analyses are difficult, because they can be calculated by monitoring the solubility change of a competitor, without monitoring that of a drug. Furthermore, the present results suggest that attention should be paid to the type of the phase solubility diagram, as well as the magnitude of the stability constant and the solubility of the complex, for a rational formulation design of CyD complexes.     

Structure and properties of electron-beam irradiated potato starch

The supermolecular structure of potato starch modified by electron-beam irradiation was studied and factors that determine its solubility in cold water were revealed. It was shown that the treatment of starch in air at doses up to 440 kGy is accompanied by its amorphization and degradation of macromolecules, whereas an increase in the amount of oxidized groups is insignificant and grain morphology remains unchanged. A decrease in the crystallinity and the degree of polymerization after irradiation results in enhancement of starch solubility in cold water from 5 to 70%.