Determination and correlation of temperature and pH value dependent solubility of dl-methionine

In order to provide basic data for the crystallization of dl -methionine and understand the thermodynamic properties of dissolution, the solubility of dl -methionine in water was measured by gravimetric method from 294.05 to 347.05 K and the solubility at different pH values under temperature 302.95 to 342.05 K was determined by elemental analysis in this work. The experimental data show that the solubility of dl -methionine increases with increasing temperature as well as more acidic or basic pH values. The van't Hoff equation, modified Apelblat equation, λh equation, Wilson model, NRTL model, and UNIQUAC model were used to correlate the solubility data versus temperature. The melting temperature, enthalpy of fusion, enthalpy and entropy of dissolution were estimated from solubility data and it shows that the expression of solubility by enthalpy and entropy of dissolution gives more reasonable estimation and Wilson model gives a better correlation for these thermodynamic properties.     

Formulation strategy towards minimizing viscosity mediated negative food effect on disintegration and dissolution of immediate release tablets

Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30?KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was measured by texture analysis. Comparison of parameters derived from force – time curves revealed a direct relation of maximum disintegration force (F_max) and disintegration force development rate (DFDR) with compressional force in fasted state, whereas an inverse relationship of F_max and DFDR with compressional force was observed in fed state. The gelling tendency of disintegrants influenced the rate of release of API in simulated fed and fasted states when compressional force was changed. These observations recommend the evaluation of formulations in simulated fed state, in the development stage, with an objective of minimizing the negative impact of food induced viscosity on disintegration. Use of disintegrants that act without gelling or can counteract the effect of gelling is recommended for tablet formulations with reduced disintegration time (DT) and mean dissolution time (MDT) in fed state, respectively.     

1-脱氧野尻霉素控释微丸的制备工艺优化及其药动学研究

1-脱氧野尻霉素控释微丸采用挤出滚圆和流化床方法进行制备。首先使用羟丙基甲基纤维素和微晶纤维素等辅料制备分散体、丸芯，再使用羟丙基甲基纳米纤维素邻苯二甲酸酯作为主要包衣材料进行包衣，并装入胶囊。采用SEM观察微丸的微观形态，以及测定其产率、脆碎度、密度、水分含量和粒径分布等物理性质，研究结果显示微丸性质符合中国药典标准规定。在体外释药试验中，溶出介质和放置方式对药物释放无显著影响，释放过程符合Baker-Lonsdale模型。对比研究1-脱氧野尻霉素原料药、分散体微丸和控释微丸在比格犬体内的控释特性，结果表明：与1-脱氧野尻霉素原料药相比，分散体微丸和控释微丸分别使1-脱氧野尻霉素的生物利用度提高了183.37%和243.87%。此外，1-脱氧野尻霉素控释微丸的体内-体外研究的相关性分析可知体外溶出和体内吸收之间呈现良好的线性关系。     

Dissolution of multicomponents during hydrothermal leaching of LF desulfurization slag

In light of the multicomponent dissolution equilibrium during the hydrothermal leaching of LF desulfurization slag, thermodynamic calculations were made and the dissolution equilibrium curves of calcium, aluminum and sulfur were plotted to analyze the interactions between these components and their influence on sulfur leaching. Furthermore, slag leaching experiments were conducted to investigate variation of pH and concentration of major components in the leaching solution. The results show that CaS(s) is easily soluble in water, and when pH>11. 4, CaS(s) dissolves to form Ca(OH)2(s). Use of hydrothermal leaching for sulfur removal from LF desulfurization slag is theoretically feasible. CaSO4(s) is difficult to dissolve and its solubility is always lower than that of CaS(s); therefore, slag oxidation affects negatively sulfur leaching. However, when the pH of the leaching environment is controlled to be above 12. 3, CaSO4(s) is gradually transformed into Ca(OH)2(s). Al2(SO4)3(s) is easily soluble, and it is unlikely that Al will react with sulfur in the solution to form a precipitate. The pH of the leaching solution rises with time and remains at about 12. Calcium concentration in the leaching solution is high, while Al concentration is low. Sulfur concentration in the solution increases with time, and Al in the slag has little effect on sulfur leaching. It is thus concluded that hydrothermal leaching is effective in removing sulfur from LF desulfurization slag.     

Interactive Mixture as a Rapid Drug Delivery System

The effectiveness of an interactive mixture as a rapid drug delivery system is compared with that of a solid dispersion. The influences of drug load, particle size, and crystallinity of these test systems are investigated. The interactive mixtures and solid dispersions were prepared from polyethylene glycol (PEG) 3350 and hydrophobic nifedipine drug by means of physical mixing and melting methods, respectively. The formed products were subjected to drug particle size and crystallinity analyses, and dissolution tests. In comparison with the interactive mixtures, the solid dispersions with low drug load were more effective as a rapid drug delivery system, as the size of a given batch of drug particles was markedly reduced by the molten PEG 3350. The rate and extent of drug dissolution were mainly promoted by decreasing effective drug particle size. However, these were lower in the solid dispersions than in the interactive mixtures when a high load of fine drug particles was used as the starting material. This was attributed to drug coarsening during the preparation of the solid dispersion. Unlike solid dispersions, the interactive mixtures could accommodate a high load of fine drug particles without compromising its capacity to enhance the rate and extent of drug dissolution. The interactive mixture is appropriate for use to deliver a fine hydrophobic drug in a formulation requiring a high drug load.     

Effect of polymers and media type on extending the dissolution of amorphous pioglitazone and inhibiting the recrystallization from a supersaturated state

Amorphous forms of crystalline drug are widely utilized for bioavailability enhancement of low solubility drugs in the pharmaceutical industry. Polymers have been found to be effective crystallization inhibitors for amorphous forms in solid states during storage or in liquid states during dissolution process. The dissolution and crystallization behaviors of these amorphous forms in the presence or absence of polymers are still far from adequately understood especially in different dissolution environments. The objective of this study was to investigate the effects of polymers and media type on extending the dissolution of amorphous pioglitazone and inhibiting the recrystallization from a supersaturated state. Polyvinylpyrrolidone K30 (PVPK30), polyvinylpyrrolidone K90 (PVPK90), polyethylene glycol 6000 (PEG6000), polyethylene-polypropylene glycol 188 (F-68), hydroxypropylmethylcellulose (HPMC) and beta-cyclodextrin (β-CD) were employed to understand these behaviors changes because these polymers were used widely. Three solutions including neutral water and phosphate buffer solutions (PBS, pH6.8 and pH7.4) were adopted as dissolution media to determine the behaviors changes comprehensively. In the presence of polymers, dissolution and solubility were extended to different degrees in three media. Polymers can delay the crystallization routes dependently of the medium type. Buffer salts in media reduced the dissolution and accelerated the crystallization process. Crystallization inhibition of these polymers was strongly dependent on the type and pH of media. HPMC displayed the strongest crystallization inhibition effects, resulting in the greatest degree of maintaining a supersaturated state that can sustain most effectively for biologically relevant timeframes.     

钨铼合金电化学溶解及沉淀分离研究

针对钨铼合金废料,采用电化学溶解法使钨、钼、铼在氢氧化钠溶液中完全溶出,再采用氯化钙沉钨钼和氯化钾沉铼进行了电解溶液的选择性沉淀分离,研究并确定了钨铼合金废料电化学溶解和沉淀分离的适宜工艺参数。结果表明:槽电压2.5 V,NaOH浓度100 g·L~(-1),电解温度30～40℃,极距20～30 mm,钨铼离子总浓度控制在30～35 g·L~(-1)时,钨、钼、铼溶出率均大于99.00%,电流效率高达99.00%以上,钨钼铼废丝和钨铼边角料的电溶能耗分别为1.43和2.28 kW·h·kg~(-1),丝状废料较块状废料更好电溶。当反应温度80℃,CaCl_2用量为3倍理论用量,溶液OH~-浓度9.5 g·L~(-1),溶液W离子浓度为23.18 g·L~(-1),反应时间2 h时,钨、钼沉淀率分别为99.86%和99.55%,得到CaWO_4/CaMoO_4白色混合物沉淀,其SEM形貌主要为球形颗粒。经过上述2道工序后,钨、钼回收率分别达到98.86%和98.55%,且制得KReO_4白色晶体。     

固态Cu-9wt%P合金在液态铝中溶解过程的研究

本文以固态Cu-9wt%P合金为研究对象,研究了973 K时固态Cu-9wt%P在铝液内的溶解过程。通过静态溶解和水淬实验得到了保留溶解过程信息的凝固组织。采用ZEISS Axio Vert.A1光学金相显微镜、扫描电子显微镜(Scaning electron microscope, SEM)对凝固组织进行了分析。研究发现固态Cu-9wt%P合金在铝液内溶解时,随着溶解时间的延长,固液界面上Cu-9wt%P合金一侧易形成单相Cu₃P,固液界面前沿富集有颗粒和层状的AlP。总结了固态Cu-9wt%P合金在铝熔体的溶解过程,揭示了溶解速度慢的根本原因。。     

Electrochemical dissolution and passivation of laser additive manufactured Ti6Al4V controlled by elements segregation and phases distribution

The electrochemical dissolution and passivation of laser additive manufactured Ti6Al4V were investigated through Tafel polarization, potentiostatic polarization and AC impedance measurements. The results show that the solution treatment−aging (STA) process aggravates the element micro-segregation compared to the annealing process, leading to varied Al and V contents of the phases from different samples. It is proven that either Al-rich or V-rich condition can highly affect the electrochemical dissolution behaviors due to thermodynamical instability caused by element segregation. The dissolution rate in the metastable passivation process is controlled by the stability of the produced film that is affected by phases distribution, especially the difficult-to-dissolve phase. And then, the dissolution rate of the phases in the transpassivation region is consistent with the rank in the activation process because the dense film is not capable of being produced. Compared to the annealed sample, the higher dissolution rate of the STA sample is beneficial to the electrochemical machining (ECM) of Ti6Al4V.