Influence of water on the solubility of two steroid drugs in hydrofluoroalkane (HFA) propellants

The objective of this research work was to investigate the influence of water level, temperature, and propellant composition on the solubility of two hydrophobic steroid drugs, triamcinolone acetonide (TAA) and beclomethasone diapropionate (BDP). pMDIs containing TAA or BDP, spiked water, and propellant blend with different ratios of HFA 134a and HFA 227 were prepared. The contents of the prepared pMDIs were filtered through a 0.22 mm Acrodisc, syringe filter into a receiving canister after the pMDIs were equilibrated at 15°C, 25°C, 30°C, and 40°C. The drug concentration in the receiving canisters was determined by HPLC and the drug solubility in the propellant blend was calculated. Also, the drug crystal collected on the filter from the donor pMDIs were characterized by x-ray diffraction. The solubility of TAA and BDP varied with propellant composition at all experimental temperatures investigated. The solubility of TAA and BDP increased as the temperature was increased at all propellant compositions and water levels studied, but decreased as the water level in the propellant system was increased at all compositions and temperatures. The x-ray diffraction results indicated that the water in the propellant system had no significant influence on the crystal characteristics of TAA in HFA propellant system, but had a significant impact on the crystal characteristics of BDP was higher than TAA at all propellant compositions, experimental temperatures and water levels investigated. The solubility of TAA and BDP was not only influenced by propellant composition and storage temperature, but also depended on the water level in the propellant system. As a consequence, the crystallinity of the drugs formulated in HFA propellant was influenced by the temperature, propellant composition and the water level in the propellant system. The impact of these factors on the crystallinity of formulated drugs.     

Inhibition of mild steel corrosion in HCl using pineapple leaves (<Emphasis Type="Italic">Ananas comosus L.</Emphasis>) extract

The corrosion inhibition of mild steel in HCl by pineapple leaves extract was studied using weight loss and hydrogen evolution methods at 30–60 °C. It was found that the pineapple leaves extract inhibited the acid induced corrosion of mild steel. The inhibition efficiency increases with increase in the extract concentration and with rise in temperature. Adsorption of the extract was found to obey Langmuir adsorption isotherm at all the concentrations and temperatures studied. The mechanism of chemical adsorption is proposed from the trend of inhibition efficiency with temperature. The proposed mechanism was also corroborated by kinetic and thermodynamic parameters obtained.     

钒电池负极电解液V2（SO4）3溶解性规律

对钒电池负极电解液中活性物质V(III)在不同硫酸浓度、不同温度条件下的溶解性规律进行了深入研究,同时对V(III)-H2SO4体系电化学性能进行了初步探讨.结果表明:V(III)的溶解是一个放热过程,在15~40℃范围内,V(III)的溶解度随着温度升高而逐渐降低;并且溶液中V(III)会以V O V形式形成二聚体,在低硫酸浓度下,V(III)可以高浓度长时间稳定存在,随硫酸浓度的增大,V(III)溶解度逐渐降低,其中30℃、1 mol/L H2SO4条件下V(III)浓度可高达2.730 mol/L;进一步通过电化学测试,发现V(III)-H2SO4体系是不可逆体系,H2SO4浓度的增大有益于提高V(III)/V(II)氧化还原反应的可逆性.     

Electrochemical and thermodynamic studies to evaluate inhibition effect of 2-[(4-phenoxy-phenylimino)methyl]-phenol in 1 M HCl on mild steel

Inhibition of the corrosion of mild steel in 1.0 M HCl solution by a Schiff base compound named 2-[(4-phenoxy-phenylimino)methyl]-phenol (APS) was investigated at different temperatures (25–55 °C) using electrochemical measurements. The inhibition efficiency increased as APS concentration and temperature increased. It was found that adsorption for APS on mild steel complies with the Langmuir adsorption isotherm in all studied temperature. Thermodynamic parameters (ΔG_ads, ΔH_ads and ΔS_ads) for APS adsorption on mild steel were found out and discussed at each temperature. Time dependency of mild steel in 1.0 M HCl solution in the absence and presence of APS was also studied. The surface morphology of mild steel was examined via SEM analysis.     

Preformulation Development of a Human Leukocyte Elastase Inhibitor for Oral Dosage

Abstract

WIN 64733 solubility and partition coefficients were determined with a precise and accurate HPLC method. Solubility decreased with increasing pH (140 mg/mL at pH 2.0, 86 mg/mL at pH 3.8, and 48 mg/mL at pH 5.2) but equilibrated within 30 hours. In purified water the maximum concentration was 102 mg/mL with pH 3.6. The maximum solubility in hydroxypropyl-beta-cyclodextrin (HP-β-CD) is only 43 mg/mL. However, unlike the water solution, the cyclodextrin preparation did not precipitate when added to 0.1 N HCl or 0.9% NaCl. The precipitated chloride salt of WIN 64733 is amorphous. Excess compound that was wetted, but not dissolved, formed liquid crystals.

In human gastric fluid (HGF), WIN 64733 did not decompose in the solid or liquid state for 2 hours, or precipitate from solution despite NaCl and HCl in the HGF. WIN 64733 solid is stable to heat (50°C), light (1000 ft-candles), humidity (75% RH), and heat plus humidity for 6 weeks. Solutions of WIN 64733 are unstable, with first-order decomposition rates that are light independent at pH's 2.0 to 6.6. Decomposition was more rapid at higher pH's and increased temperature. This occurred by hydrolysis of the ester linkage forming an N-hydroxymethyl fragment that subsequently decomposed to saccharin and formaldehyde, verified by the Hantzsch reaction.

Since solubility is high in water and HGF, dissolution in the gastric environment would favor absorption of an oral dose.     

Microstructure evolution and photoluminescence in nanocrystalline Mg(x)Zn(1 - x)O thin films

The effects of Mg concentration and annealing temperature on the characteristics of nanocrystalline Mg(x)Zn(1 - x)O thin films (where x = 0-0.4) were studied using electron microscopy and photoluminescence. The films were prepared by a sol-gel method. The solid solubility limit of MgO in ZnO for the sol-gel-derived Mg(x)Zn(1 - x)O films in the present study was determined to be ～ 20 at.%. Microstructural characterization of the films showed that the wurtzite crystallites decrease in size with increase in Mg concentration up to the solubility limit. Increasing Mg concentration beyond the solubility limit resulted in a decrease in crystallinity of the films. The bandgap energy was found to increase with Mg concentration whereas the linewidth first increased and then decreased when the Mg concentration was increased beyond the solubility limit. Photoluminescence properties have been correlated to the microstructure of the films. A growth mechanism for Mg(x)Zn(1 - x)O nanocrystalline films under the present processing conditions has also been proposed.     

Leaching of the fine fraction of the argon oxygen decarburization with lance (AOD-L) sludge for the preferential removal of iron

The fine fraction of the argon oxygen decarburization with lance (AOD-L) sludge is a hazardous waste generated by the stainless steel industry which is normally disposed in landfills. Due to the relative high content of Fe, Cr and Ni as well as its low granulometry, a hydrometallurgical route based on sequential leaching steps is being investigated to treat it. In this paper, an attempt made to remove Fe from the sludge and concentrate Cr and Ni in the solid is highlighted. Leaching was carried out at atmospheric pressure using H(2)SO(4) and HCl at varying temperature (25, 40, 55 and 70 degrees C) and acid concentration (3, 6 and 12%, v/v). For both acids, leaching rate increased with temperature and acid concentration, and higher dissolutions of Fe and Ni were obtained in comparison with that of Cr. HCl was found more selective for Fe over Ni and Cr. The content of Fe was reduced nearly 50% (w/w) at 70 degrees C and HCl 12% (v/v), while Cr remained mostly in the solid; however, around 40% (w/w) of Ni was dissolved and it may hinder such leaching step in the studied route. The study points out that total metal leaching of sludge under high temperature and pressure conditions must be considered.     

用焦磷酸络锰(Ⅲ)引发丙烯酰胺接枝魔芋粉合成增稠剂

用焦磷酸络锰的三价离子Mn^3 为引发剂，引发魔芋粉（KGM）与丙烯酰胺（AM）的接枝共聚。研究了引发剂浓度、单体浓度、pH值、反应温度、反应时间、反应介质以及KGM预处理方式等对接枝反应的影响，同时，还研究了产物的水溶性及增稠性。     

Use of magnesit as a magnesium source for ammonium removal from leachate

Using magnesit (MgCO(3)) as a low cost source of magnesium ions in the struvite precipitation for the removal of high ammonium content of leachate was evaluated. Optimum molar concentration and pH conditions were analyzed to minimize the struvite solubility. Since solubility of magnesit in water is low, HCl was used to obtain soluble Mg. Maximum soluble Mg was obtained for the addition of 2 M HCl to the 1 M MgCO(3). Struvite precipitation with magnesit was effective for the removal of ammonium, suspended solid, phosphate and turbidity. Economical evaluation was made comparing the costs of two magnesium sources, MgCl(2) and MgCO(3). The economical analysis has shown that operation cost of struvite precipitation can be reduced about 18% by using MgCO(3) instead of MgCl(2). High salt concentration after struvite precipitation has no inhibitory effect on the anaerobic reactor performance.     

Preformulation Studies on the S-Isomer of Oxybutynin Hydrochloride,an Improved Chemical Entity (ICE™)

(S)-Oxybutynin HCl (S-OXY) is a white crystalline solid powder with an acicular particle morphology. Differential scanning calorimetry (DSC) thermograms revealed one characteristic endotherm at 116.2°C. On rescanning a sample heated to 120°C, no thermal events were distinguished in the temperature range 25°C to 150°C. Weight loss curves determined by thermogravimetric analysis showed a continuous, gradual weight loss of about 0.15% over the temperature range 30°C to 110°C, followed by a change in slope and more rapid weight loss beginning at 150°C. Observation by hot-stage microscopy confirmed the melting endotherm observed by DSC. Equilibrium moisture uptake studies indicated low water vapor uptake at low relative humidities (< 52.8%). At relative humidities of 75.3% and 84.3%, S-OXY first deliquesced and then converted to a lower melting point crystal form. X-ray powder diffraction (XRPD) data supported the DSC findings. S-OXY underwent degradation by ester hydrolysis at alkaline pHs. The kinetics of this reaction were studied at 25°C in carbonate-bicarbonate buffers. Observed rate constants of 0.008 h^?1 and 0.0552 h^?1 were determined at pH 9.69 and 10.25, respectively. The pK_a of S-OXY was 7.75. The aqueous solubility of S-OXY was described as a function of pH and the free-base solubility. The mean partition coefficient log P was 3.33 using 1-octanol. The surface tensions of aqueous solutions of S-OXY decreased with increasing concentration, but no concentration-independent region was observed, indicating that S-OXY does not form micelles in aqueous solution. The dissolution rate of S-OXY from a compressed disk in 0.1 N HCl was rapid, whereas it was considerably slower at pH 7.4. Addition of 1% hexadecyltrimethylammonium bromide (CTAB) at pH 7.4 significantly improved the dissolution rate. S-OXY displayed very poor flow properties when compared to standard pharmaceutical excipients. XRPD results indicated that S-OXY exhibited a loss in crystallinity following ball milling. Hiestand tableting indices indicated that S-OXY has good bonding properties and forms strong compacts, but is likely to be susceptible to capping on ejection from the die. This indicated the need for a plastically deformable excipient such as Avicel PH-101 in tablet formulations.     

Nb掺杂TiO2压敏陶瓷的施主掺杂固溶度

研究了不同烧结温度TiO2压敏陶瓷的显微结构、施主掺杂固溶度和电学性能。采用SEM和EDS测试了其显微结构和晶粒化学组成。随烧结温度增加,TiO2晶粒迅速长大,显微结构均匀致密,但过高的烧结温度将导致较多气孔。1350℃为比较合适的烧结温度,其晶粒大小为15μm左右。在施主掺杂浓度一定的条件下,施主掺杂离子Nb5+在TiO2晶粒中的固溶度、晶粒电子浓度和电导率随烧结温度上升而增加,晶粒电阻率随烧结温度上升而下降。以能谱中O为参考确定TiO2晶格数量计算得到的固溶度及其电学性能更符合实验测试结果。     

Itraconazole formulation studies of the melt-extrusion process with mixture design

Itraconazole is a poorly water soluble compound. One method to increase the aqueous solubility of itraconazole is through formation of a solid dispersion. The purpose of this study is to develop a 40% w/w itraconazole formulation through solid dispersion formation, using hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and hydroxypropylmethyl-cellulose (HPMC) as mixture components. The solid dispersion was obtained by melt-extrusion using a twin-screw corotating melt extruder. A D-optimal mixture design was applied for the development of the optimal itraconazole formulation. The itraconazole fraction varied between 20% w/w and 50% w/w in the mixture design and the HPMC and HP-beta-CD fractions varied between 10% w/w and 60% w/w. The itraconazole formulation was optimized by producing clear extrudates, minimizing the torque, and maximizing the glass transition temperature and the apparent itraconazole solubility in 0.1 N HCl. Regression models were developed for the torque, glass transition temperature, and apparent solubility of itraconazole. High itraconazole fraction in the mixture promoted a better melt processing (minimizes torque). High HPMC fraction (>33% w/w) resulted in clear extrudates, indicating a solid dispersion and resulted in high glass transition temperature of the melt. High HP-beta-CD fraction resulted in increased apparent itraconazole solubility in 0.1 N HCl. The optimal itraconazole formulation consisted of 45% w/w HPMC and 15% HP-beta-CD w/w.     

高浓度CO2在MEA溶液中平衡溶解度的实验研究

采用气液搅拌平衡装置,通过酸碱滴定和皂泡流量计测定了高浓度CO2在不同MEA溶液中的平衡溶解度。利用正交实验设计方法,考察了温度、CO2分压力、MEA质量浓度等因素对CO2平衡溶解度的影响。结果表明,在实验参数选定范围内,影响MEA中CO2平衡溶解度的因素主次顺序为：CO2分压力〉MEA质量浓度〉温度;MEA溶液中CO2的平衡溶解度随压力的增大而增大,随MEA质量浓度的增大而减小,随温度的增大而减小。     

不同引发剂体系对氧化铝浆料固化过程的影响

研究了引发剂体系对氧化铝浆料固化过程的影响. 通过测试丙烯酰胺(AM)水溶液聚合过程的弹性模量曲线, 考察了引发剂体系对丙烯酰胺(AM)和N,N’-亚甲基双丙烯酰胺 (MBAM)水溶液交联聚合过程的影响. 引发剂体系分别为过硫酸铵(APS)、过硫酸铵-四甲基乙二胺(APS-TEMED)氧化还原体系和2,2’-偶氮[2-(2-咪唑啉-2-基)丙烷]盐酸盐(AZIP·2HCl). 三种引发剂中AZIP\cdot2HCl引发的聚合产物的模量在40～50℃都比较高; 温度对闲置时间影响较大, 更容易控制固化进程. AZIP·2HCl引发的50vol%浆料固化的模量曲线表明温度和引发剂浓度对浆料固化影响较大. 比较了三种引发剂引发的50vol%氧化铝浆料的固化过程模量曲线, 50℃时AZIP·HCl引发的浆料固化后的湿坯的弹性模量达到2.3×10⁶Pa, 比APS(1.58×10⁶Pa,55℃)和APS--TEMED(1.58×10⁶Pa, 25℃)引发的浆料固化后的湿坯模量要高.     

Solubility of Various Sulfonamides in N-Alkanols I. Effect of Polarity and Temperature

The solubilities of several sulfonamides were studied at three temperatures over a wide spectrum of polarity of normal alcohols. The sulfonamides chosen for study were sulfasoxaeole, sulfadimethoxine, sulfasomidine and sulfadiazine and their solubility behavior in various alcohols such ae methanol through 1-decanol at 25°. 30° and 37°.

Solubility in alcohols was found to increase with temperature and the rank order of solubility at any temperature wae found to be in the general order of sulfasoxizole, sulfadimethoxine, sulfasomidine and sulfadiaeine. Solubility was found to be highest in methanol and diminished with increasing chain length of the alcohol.

The solubility magnitude for several of the sulfonamides gave an interesting reversal in 1-decanol and all the results obtained are discussed further in this communication.     

Polyaniline as a Gas-Sensor Material

Polyaniline (PANI) was synthesized by oxidative polymerization of aniline using ammonium persulfate in an acid medium. The polyaniline salt was converted to base form by treatment with ammonium hydroxide. The polyaniline base was dissolved in N-methyl pyrrolidone (NMP) for film casting. The cast film was doped with HCl for obtaining higher conductivity. Both doped and undoped PANI films were characterized by UV-visible, FTIR, and XRD analyses. The electrical conductivity of the PANI film was studied by a four-point probe method at room temperature. Finally, ammonia gas-sensing characteristics of the prepared polyaniline film were studied by measuring the change in electrical conductivity on exposure to ammonia gas at different concentrations. The influence of concentration of acid during polymerization of aniline and dopant concentration on the gas sensing characteristics of PANI film are reported in this paper.     

Synthesis of aligned zinc sulfide nanostructures and the influence of experimental conditions on their morphologies and phase

A novel aligned flower-like array and single-crystal nanosheets composed of ZnS quantum wires were fabricated via a simple solution route. In the method, ZnCl2 chemicals reacted with Na2S in 50 ml of ethylenediamine (en) solution containing different amounts of hydrochloric acid (HCl) at 70-80 degrees C. After annealing at 500 degrees C for 1.5 h, wurtzite phase ZnS nanoscaled materials were synthesized. When the amount of HCl was 2 ml and 3 ml, respectively, flower-like structure and nanosheets were obtained. The products were characterized by X-ray diffraction, transmission electron microscopy, high-resolution electron microscopy (HREM), and electron diffraction (ED). The influences of concentration, temperature, and reaction time on the morphologies and phase of ZnS nanostructures were also studied. The photoluminescence peaks are located at approximately 308 nm and approximately 410 nm. The formation mechanism is also discussed here.     

化学复合镀梯度镀层工艺研究

研究了梯度复合镀层Ni-P／Ni-P-PTFE／Ni-Cu-P-PTFE的形成工艺,探讨了镀液的温度、pH值、阳离子表面活性剂浓度、PTFE浓度以及镀层中的铜含量对Ni-Cu-P-PTFE镀层的沉积速度、组成和耐蚀性的影响,分别用数字测微计和能量分散X射线光谱测量了涂层厚度和组成,Ni-Cu-P-PTFE镀层在HCl和NaCl溶液中的抗蚀性研究表明,Ni-Cu-P-PTFE镀层的耐蚀性优于Ni-P-PTFE镀层和铜．     

Preformulation studies on the S-isomer of oxybutynin hydrochloride, an Improved Chemical Entity (ICE).

(S)-Oxybutynin HCl (S-OXY) is a white crystalline solid powder with an acicular particle morphology. Differential scanning calorimetry (DSC) thermograms revealed one characteristic endotherm at 116.2 degrees C. On rescanning a sample heated to 120 degrees C, no thermal events were distinguished in the temperature range 25 degrees C to 150 degrees C. Weight loss curves determined by thermogravimetric analysis showed a continuous, gradual weight loss of about 0.15% over the temperature range 30 degrees C to 110 degrees C, followed by a change in slope and more rapid weight loss beginning at 150 degrees C. Observation by hot-stage microscopy confirmed the melting endotherm observed by DSC. Equilibrium moisture uptake studies indicated low water vapor uptake at low relative humidities (<52.8%). At relative humidities of 75.3% and 84.3%, S-OXY first deliquesced and then converted to a lower melting point crystal form. X-ray powder diffraction (XRPD) data supported the DSC findings. S-OXY underwent degradation by ester hydrolysis at alkaline pHs. The kinetics of this reaction were studied at 25 degrees C in carbonate-bicarbonate buffers. Observed rate constants of 0.008 h(-1) and 0.0552 h(-1) were determined at pH 9.69 and 10.25, respectively. The pKa of S-OXY was 7.75. The aqueous solubility of S-OXY was described as a function of pH and the free-base solubility. The mean partition coefficient log P was 3.33 using 1-octanol. The surface tensions of aqueous solutions of S-OXY decreased with increasing concentration, but no concentration-independent region was observed, indicating that S-OXY does notform micelles in aqueous solution. The dissolution rate of S-OXY from a compressed disk in 0.1 N HCl was rapid, whereas it was considerably slower at pH 7.4. Addition of 1% hexadecyltrimethylammonium bromide (CTAB) at pH 7.4 significantly improved the dissolution rate. S-OXY displayed very poor flow properties when compared to standard pharmaceutical excipients. XRPD results indicated that S-OXY exhibited a loss in crystallinity following ball milling. Hiestand tableting indices indicated that S-OXY has good bonding properties andforms strong compacts, but is likely to be susceptible to capping on ejection from the die. This indicated the needfor a plastically deformable excipient such as Avicel PH-101 in tablet formulations.     

Apparent solubility of drugs in partially crystalline systems

Using several griseofulvin samples, representing different solid-state structures, the solubility behavior of drugs in both one-state (totally ordered, semiordered or disordered) and two-state systems was studied. Special attention was directed towards the surface structure of the particles. The partially crystalline samples were obtained by milling the raw material (crystalline standard) or storing the quenched sample (amorphous standard). The solid-state structure of the materials was studied using x-ray diffraction (XRD), differential scanning calorimetry (DSC), isothermal microcalorimetry (IMC), and scanning electron microscopy (SEM). The saturation concentration of the materials was studied in suspensions containing different dispersion concentrations of drug after centrifugation and filtration, using spectrophotometry. In all cases these dispersion concentrations exceeded the solubility of the drug. The solubilities were plotted vs. dispersion concentrations for each sample. Several solubility plateaus were found. The lowest and highest solubility plateaus corresponded to the solubilities of crystalline and amorphous standards. These plateaus were reached at 8 and 44 µg/mL for crystalline and amorphous griseofulvin standards, respectively. An intermediate plateau served as an indication of the existence of a totally semiordered structure. This was reached at 19 µg/mL for griseofulvin. Any deviation from these plateaus was suggested to be indicative of the existence of heterogeneity on the surface structure, which in most cases could be described as a two state system. In such cases, the apparent solubility was a function of dispersion concentration, until at very high dispersion concentrations (4000-20,000 µg/mL) the saturation concentration of the totally disordered (44 µg/mL) or semiordered (19 µg/mL) one-state phase was reached. No reduction in these values was observed during storage for 50 days. It is thus concluded that, in partially crystalline systems, the saturation concentration is an interfacial phenomenon, which depends on the amount, reactivity, and solid-state structure of the exposed solid surfaces in equilibrium with the solution. A simplified solubility model is proposed to qualitatively describe the relationship between established apparent solubilities (saturation concentrations) and different combinations of solid-state structures.