Increasing the solubility of drugs through cyclodextrin complexation

The bioavailability of pharmaca which dissolve in water only with difficulty is very limited. The cyclodextrins /CDs/, and primarily -CD and -CD, were successfully applied to increase the dissolution characteristics and hence the bioavailability of drugs: furosemide, hydrochlorothiazide, mebendazole, metronidazole, spironolactone, tofisopam, vinpocetine base, etc. From these pharmaca, products were made by mixing, kneading, grinding, freeze-drying, spray-embedding and precipitation.The more important factors on which the dissolution and bioavailability of the drugs depend are concluded.     

Increasing the solubility characteristics of iomeglamic acid withβ-cyclodextrin

Iomeglamic acid has been successfully applied for radioscopy of the gall-bladder since 1972. This pharmacon has the disadvantageous property that it is practically insoluble in water. Preparations containing the drug in different concentrations were made with-cyclodextrin by different methods, and their dissolution characteristics were determined. In the best situation the solubility increased ten-fold. The tablets were made from the most suitable complex, with-cyclodextrin. The conditions of tableting, the parameters and the dissolution of the tablets were tested.     

相溶解度法研究环糊精对蒽醌药物的增溶作用

通过相溶解度法,测定1,2-二氨基蒽醌、1,4-二氨基蒽醌和1,8-二羟基蒽醌在不同温度、不同浓度的β-环糊精(β-CD)、羟丙基-β-环糊精(HP-β-CD)以及羟乙基-β-环糊精(HE-β-CD)中的溶解度,绘制相溶解度曲线,并进行回收率及稳定性实验.实验结果表明:1,2-二氨基蒽醌、1,4-二氨基蒽醌和1,8-二羟基蒽醌的溶解度均随3种环糊精浓度的增加而呈线性增加,相溶解度曲线为AL型,蒽醌与环糊精形成的包合物类型为1∶1型,3种环糊精对蒽醌均有增溶作用,增溶效应顺序为HP-β-CDHE-β-CDβ-CD,与HP-β-CD作用顺序为1,2-二氨基蒽醌1,4-二氨基蒽醌1,8-二羟基蒽醌.     

Increasing the solubility characteristics of D-norgestrel with cyclodextrins

Levonorgestrel dissolves only slightly in water. Attempts were made to increase the solubility properties of this drug by complexing with cyclodextrins. The products were investigated with a dissolution tester and a Sartorius resorption model. X-ray and NMR spectra of the inclusion complexes were analysed.     

Development of a Total Organic Carbon method for the quantitative determination of solubility enhancement by cyclodextrins: Application to essential oils

Formation of inclusion complexes with cyclodextrins (CDs) is known to enhance guest solubility in aqueous medium. Different techniques allow determining the evolution in solubility of individual guest compounds. However, examination of mixtures solubility encapsulated in CDs is still a challenge. This is mainly related to the difference in the response of mixture components to the applied technique or to the fact that most of the conventional methods examine the signal of an individual constituent of the mixture. Thus, applying current techniques may not reflect the behavior of the whole mixture. Here, we used for the first time Total Organic Carbon (TOC) analysis to explore and assess the efficiency of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to enhance the solubility of natural complex mixtures such as essential oils (EOs). Phase solubility studies were performed for eleven EOs with HP-β-CD. The TOC method has provided good validation parameters for linearity, precision and accuracy. For further validation of the method, phase solubility studies were performed with HP-β-CD for eugenol, as a model EO component. The eugenol solubility was determined by UV–Visible and TOC analyses in order to compare the results. Data obtained from both methods were similar (p < 0.05), thereby proving the effectiveness of the developed TOC method. Finally, the phase solubility diagrams of EOs showed that the solubilizing potential of CD increased proportionally with the decrease in EO intrinsic solubility. Results proved that TOC could be successfully applied to investigate CD/guest inclusion complexes and is expected to have a broad range of applications in the field of mixtures encapsulation.     

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。     

A molecular‐level computational study of the diffusion and solubility of water and oxygen in carbonaceous polyethylene nanocomposites

Monte Carlo and molecular dynamics simulations were performed to investigate the effect on the solubility, diffusion, and permeability of water and oxygen when adding graphene or single‐walled carbon nanotubes (SWCNTs) to polyethylene (PE). When compared with pure PE, addition of graphene lowered the solubility of water, whereas at lower temperatures, the oxygen solubility increased because of the oxygen–graphene interaction. Addition of SWCNTs lowered the solubility of both water and oxygen when compared with pure PE. A detailed analysis showed that an ordered structure of PE is induced near the additive surface, which leads to a decrease in the diffusion coefficient of both penetrants in this region. The addition of graphene does not change the permeation coefficient of oxygen (in the direction parallel to the filler) and, in fact, may even increase this coefficient when compared with pure PE. In contrast, the water permeability is decreased when graphene is added to PE. The addition of SWCNTs decreases the permeability of both penetrants. Graphene can consequently be added to selectively increase the solubility and permeation of oxygen over water, at least at lower temperatures. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 589–602     

The solubility limit of a solid solutions for the systems of long-chain symmetrical ketones in ann-alkane matrix

The systems of long-chain symmetrical ketones inn-alkane matrices form solid solutions for a low concentration range of the ketone, when the number of carbon atoms n in a ketone molecule Kn is equal to or lower than that in an-alkane molecule. The Kn examined were K25 to K39. The purity of all the samples used was very high. The solubility limit of these solid solutions was determined with DSC measurements. Above the solubility limit (the critical concentration) the systems changed to eutectic mixtures. The relationships for the solubility limit were derived, taking into consideration the lateral two-dimensional and the longitudinal positioning along the chain axes and the correlating energies. The multiplicity of the longitudinal positioning led to a remarkable increase in the solubility limit of the systems of Kn/Cn (n>n). The present result points to the importance of the entropy of mixing and also for the stability of long-chain crystals.     

Environmentally friendly procedure for the aqueous oxidation of benzyl alcohols to aldehydes with dibromodimethylhydantoin (DBDMH) and cyclodextrin: Scope and mechanistic insights

Reported herein is an environmentally friendly procedure for the oxidation of benzyl alcohols to aldehydes using an inexpensive, commercially available reagent, 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), and a variety of cyclodextrin additives under fully aqueous solvent conditions. This reaction proceeds with moderate to good yields for a broad scope of benzyl alcohol substrates, with the cyclodextrin acting to enhance the desired reactivity and limit undesired aromatic bromination side products. The reported experiments provide substantial mechanistic insight that will drive further reaction optimization and have broad-reaching applications.     

An improved model for mass transfer during the formation of polymeric membranes by the immersion-precipitation process

An analysis is presented, which describes the isothermal ternary diffusion process encountered in the formation of a cellulose acetate polymeric membrane by a direct immersion-precipitation of polymeric solutions in a nonsolvent bath. A material coordinate was employed to derive the mass transfer equations for the membrane solution and the convective mass transfer in the coagulation bath was taken into account by solving the hydrodynamic boundary layer equations. Diffusion coefficients were measured and used to deduce ternary phenomenological coefficients. The computed results are found to agree with the experimental precipitation time and membrane morphologies observed in scanning electron photomicrographs. © 1994 John Wiley & Sons, Inc.     

Calculation of solubility of solid solutes in mixed non-aqueous solvents within the limits of the theory of molecular association

A method for calculating the solubility of solid substances in mixed non aqueous solvents is proposed based on the theory of molecular association and a simple lattice model (ASL = Associated Solution + Lattice). This method provides the calculation of the solubility of solids in mixed non aqueous solvents using only the molecular association parameters and the value of the interchange energy ω_AB that is derived from the phase equilibrium data in a mixed solvent.     

New insights into the use of hydroxypropyl cellulose for drug solubility enhancement: An analytical study of sub-molecular interactions with fenofibrate in solid state and aqueous solutions

Hydroxypropyl cellulose (HPC) is a solubility enhancer used for poorly soluble drugs, nano-suspensions and amorphous solid dispersions (ASD). However, the underlying mechanism remains unclear. ASDs of a poorly soluble drug, fenofibrate (FEN), were analyzed using liquid nuclear magnetic resonance (NMR) and solid state NMR (ss-NMR). Liquid NMR revealed interactions between the pyranose ring of the HPC molecule and the diphenylketone from FEN. The water accessibility of the CH₃ groups in HPC and FEN is very low, they form a hydrophobic zone in aqueous solution that may sustain the drug nucleation. Moreover, ss-NMR measurements confirmed very low drug crystallinity for HPC-FEN ASDs. Cross-polarization and direct polarization ¹³C spectra, ¹³C-CPMAS and ¹³C-PARIS, distinguished the most rigid and flexible portions in concordance with the ss-NMR proton T₁ and T_1r relaxation results. Although HPC side chains (hydroxypropoxy) are the most flexible portions, their flexibility is moderate and high rigidity is the predominant. The ss-NMR proton relaxation indicates a rather homogeneous distribution of the components (HPC and FEN) in the solid mixtures. The versatile NMR methodology proposed can be used to study other polymer-drug systems and it may contribute to understand relevant functional aspects such as the rate of drug-delivery and their stability.     

水蒸气在高分子膜中吸附和传递行为的研究进展

水蒸气作为一种可凝聚性气体,导致它在高分子膜中的渗透行为比其它非凝聚性气体复杂。简要综述了水蒸气分子在高分子膜中的溶解和扩散行为,在不同的水蒸气活度下,考察了水蒸气在高分子膜中的溶解系数、扩散系数和渗透系数。分析了水分子与膜之间的相互作用,及水分子的成簇机理。     

Chemical reactions between immiscible polymers in the melt: Transesterification of poly(ethylene-co-methyl acrylate) with mono-hydroxylated polystyrenes

This article presents a unique example dealing with how chemical reactions between immiscible polymers in the melt behave differently than they would do in solution. Specifically, a model reaction was chosen: the transesterification between poly(ethylene-co-methyl acrylate) (EMA) and polystyrene mono-hydroxylated at the chain end (PSOH). It was carried out in the melt in a batch mixer. The overall rate of this reaction has a similar dependence of temperature, composition of reactants, and the nature and concentration of catalyst as in solution. The reactivity of PSOH decreases drastically with increasing molecular weight, and it becomes very weak when the molecular weight exceeds 8000 g/mol. As opposed to a reaction in solution or in a homogeneous melt, mechanical mixing increases the reaction rate since it generates interfacial area and reduces the diffusion length. The EMA-g-PS graft copolymer formed at the interfaces reduces the interfacial tension, and increases the miscibility of the reaction mixture. However, its occupation of the interfaces reduces contact between the reactive moieties, thus decreasing the overall reactivity. More importantly and much to our surprise, adding 1 to 2 wt % of an inert solvent increased greatly the overall reaction rate. While an increased interfacial mixing and diffusion by the presence of minor amounts of solvent are thought to be the major factors contributing to the drastic increase in reactivity, numerous questions still remain. Nevertheless, this study clearly showed that as opposed to a reaction in solution, mechanical mixing and the presence of minor amounts of solvent are two additional and critical means to control chemical reactions between immiscible polymer melts. © 1995 John Wiley & Sons, Inc.     

Increasing the Solubility of a Hydrophobic Molecule with Thymine-like Face by DNA via Supramolecular Interaction

Poor water-solubility of hydrophobic drugs greatly hampers drug design and creats delivery problems.The traditional way to improve the solubility is to add hydrotropes or excipients to supress aggregations.Here,a novel mechanisim has been proposed based on supramolecular interactions and demonstrated with a small molecule,pvromellitic diimide(PD).This compound contains thymine-like ‘face’ and can interact with adenines through Wat-son-Crick and Hoogsteen hydrogen-bonding.Given the high water solubility of poly adenines[poly(A)],it is expectec that poly(A)will greatly increase the PD solubility.Indeed,such an increased solubility was confirmed by ultraviolet-visible spectroscopy(UV-Vis)and polyacrylamide gel electrophoresis(PAGE)analysis.We believe that this strategy could be used to improve the solubility of other similar hydrophobic molecules.     

氧体积分数对炭黑燃烧特性影响的热天平研究

利用热天平对天然气扩散火焰中生成的炭黑在不同氧体积分数下（21%、15%、10%和5%）的燃烧特性进行了研究，选用蜡烛炭黑、4种工业炭黑以及无烟煤焦炭作为对比。基于试验结果确定了燃烧特性参数，并分析了燃烧特性。天然气扩散火焰中生成的炭黑明显早于其他试样着火燃烧，着火温度在所有试样中最低，氧体积分数为21%下为483.0℃，比焦炭约低114℃，比蜡烛炭黑低近127.8℃。自制天然气炭黑可燃指数比焦炭低，着火后前期燃烧反应能力较弱。随着氧体积分数的降低，各试样着火温度在50℃内变化。比较各试样的燃尽特性可知自制天然气炭黑在不同燃尽率下的相对燃尽时间最长，氧体积分数为21%下完全燃尽为6.03min，比焦炭长21.3%。蜡烛炭黑相对燃尽时间也较长。随着氧体积分数降低，各试样燃尽时间都延长，尤其是自制天然气炭黑，氧体积分数从21%降到5%，相对燃尽时间延长2.97倍，氧体积分数降低明显延长其燃尽过程。     

Separation and permeation characteristics of a DD3R zeolite membrane

Permeation of various gases (carbon dioxide, nitrous oxide, methane, nitrogen, oxygen, argon, krypton, neon) and their equimolar mixtures through DD3R membranes have been investigated over a temperature range of 220–373 K and a feed pressure of 101–400 kPa. Helium was used as sweep gas at atmospheric pressure. Adsorption isotherms were determined in the temperature range 195–298 K, and modelled by a single and dual site Langmuir model. The permeation flux is determined by the size of the molecule relative to the window opening of DD3R, and its adsorption behaviour. As a function of temperature, bulky molecules (methane) show activated permeation, weakly adsorbing molecules decreasing permeation behaviour and strongly adsorbing molecules pass through a maximum. Counter diffusion of the sweep gas (helium) ranged from almost zero up to the order of the feed gas permeation and was strongly influenced by the adsorption of the feed gas.

DD3R membranes have excellent separation performance for carbon dioxide/methane mixtures (selectivity 100–3000), exhibit good selectivity for nitrogen/methane (20–45), carbon dioxide and nitrous oxide/air (20–400), and air/krypton (5–10) and only a modest selectivity for oxygen/nitrogen (2) separation. The selectivity of mixtures of a strongly and a weakly adsorbing component decreased with increasing temperature and pressure. The selectivity of mixtures of weakly adsorbing components was independent of pressure.

The permeation and separation characteristics of light gases through DD3R membranes can be explained by taking into account: (1) steric effects introduced by the window opening of DD3R leading to molecular sieving and activated transport, (2) competitive adsorption effects, as observed for mixtures involving strongly adsorbing gases, and (3) interaction between diffusing molecules in the cages of the zeolite.     

Multicomponent solid forms of the uric acid reabsorption inhibitor lesinurad and cocrystal polymorphs with urea: DFT simulation and solubility study

Lesinurad (systematic name: 2‐{[5‐bromo‐4‐(4‐cyclopropylnaphthalen‐1‐yl)‐4H‐1,2,4‐triazol‐3‐yl]sulfanyl}acetic acid, C₁₇H₁₄BrN₃O₂S) is a selective uric acid reabsorption inhibitor related to gout, which exhibits poor aqueous solubility. High‐throughput solid‐form screening was performed to screen for new solid forms with improved pharmaceutically relevant properties. During polymorph screening, we obtained two solvates with methanol (CH₃OH) and ethanol (C₂H₅OH). Binary systems with caffeine (systematic name: 3,7‐dihydro‐1,3,7‐trimethyl‐1H‐purine‐2,6‐dione, C₈H₁₀N₄O₂) and nicotinamide (C₆H₆N₂O), polymorphs with urea (CH₄N₂O) and eutectics with similar drugs, like allopurinol and febuxostat, were prepared using the crystal engineering approach. All these novel solid forms were confirmed by XRD, DSC and FT–IR. The crystal structures were solved by single‐crystal and powder X‐ray diffraction. The crystal structures indicate that the lesinurad molecule is highly flexible and the triazole moiety, along with the rotatable thioacetic acid (side chain) and cyclopropane ring, is almost perpendicular to the planar naphthalene moiety. The carboxylic acid–triazole heterosynthon in the drug is interrupted by the presence of methanol and ethanol molecules in their crystal structures and forms intermolecular macrocyclic rings. The caffeine cocrystal maintains the consistency of the acid–triazole heterosynthons as in the drug and, in addition, they are bound by several auxiliary interactions. In the binary system of nicotinamide and urea, the acid–triazole heterosynthon is replaced by an acid–amide synthon. Among the urea cocrystal polymorphs, Form I (P, 1:1) consists of an acid–amide (urea) heterodimer, whereas in Form II (P2₁/c, 2:2), both acid–amide heterosynthons and urea–urea dimers co‐exist. Density functional theory (DFT) calculations further support the experimentally observed synthon hierarchies in the cocrystals. Aqueous solubility experiments of lesinurad and its binary solids in pH 5 acetate buffer medium indicate the apparent solubility order lesinurad–urea Form I (43‐fold) > lesinurad–caffeine (20‐fold) > lesinurad–allopurinol (12‐fold) ? lesinurad–nicotinamide (11‐fold) > lesinurad, and this order is correlated with the crystal structures.     

Chain-length dependence of the antifouling characteristics of the glycopolymer-modified polypropylene membrane in an SMBR

Membrane-bioreactor processes have increased considerably in recent years. However, the natural disadvantages of common membrane materials, such as hydrophobic surface, cause membrane fouling and cumber further extensive applications. In this work, hydrophilic surface modification of polypropylene microporous membranes was carried out by the sequential photoinduced graft polymerization of d-gluconamidoethyl methacrylate (GAMA) to meet the requirements of wastewater treatment and water reclamation applications. The grafting density and grafting chain length were controlled independently in the first and second step, respectively. Attenuated total reflection–Fourier transform infrared spectroscopy (FT-IR/ATR) and X-ray photoelectron spectroscopy (XPS) were employed to confirm the surface modification on the membranes. Water contact angle was measured by the sessile drop method. Results of FT-IR/ATR and XPS clearly indicated that GAMA was grafted on the membrane surface. It was found that the grafting chain length increased reasonably with the increase of the UV irradiation time. Water contact angle on the modified membrane decreased with the increase of the grafting chain length, and showed a minimum value of 43.2°, approximately 51.8° lower than that of the unmodified membrane. The pure water fluxes for the modified membranes increased systematically with the increase of the grafting chain length. The effect of the grafting chain length on the antifouling characteristics in a submerged membrane-bioreactor for synthetic wastewater treatment was investigated. After continuous operation in the submerged membrane-bioreactor for about 70 h, reduction from pure water flux was 90.7% for the virgin PPHFMM, and ranged from 80.8 to 87.2% for the modified membranes, increasing with increasing chain length. The flux of the virgin PPHFMM membrane after fouling and subsequent washing was 31.5% of the pure water flux through the unfouled membrane; for the modified membranes this ranged from 27.8 to 16.3%, decreasing with increasing chain length. These results demonstrated that the antifouling characteristics for the glucopolymer-modified membranes were improved with an increase in GAMA chain length.