Estimation of Drug–Polymer Miscibility and Solubility in Amorphous Solid Dispersions Using Experimentally Determined Interaction Parameters

Purpose  The amorphous form of a drug may provide enhanced solubility, dissolution rate, and bioavailability but will also potentially crystallize over time. Miscible polymeric additives provide a means to increase physical stability. Understanding the miscibility of drug–polymer systems is of interest to optimize the formulation of such systems. The purpose of this work was to develop experimental models which allow for more quantitative estimates of the thermodynamics of mixing amorphous drugs with glassy polymers. Materials and Methods  The thermodynamics of mixing several amorphous drugs with amorphous polymers was estimated by coupling solution theory with experimental data. The entropy of mixing was estimated using Flory–Huggins lattice theory. The enthalpy of mixing and any deviations from the entropy as predicted by Flory–Huggins lattice theory were estimated using two separate experimental techniques; (1) melting point depression of the crystalline drug in the presence of the amorphous polymer was measured using differential scanning calorimetry and (2) determination of the solubility of the drug in 1-ethyl-2-pyrrolidone. The estimated activity coefficient was used to calculate the free energy of mixing of the drugs in the polymers and the corresponding solubility. Results  Mixtures previously reported as miscible showed various degrees of melting point depression while systems reported as immiscible or partially miscible showed little or no melting point depression. The solubility of several compounds in 1-ethyl-2-pyrrolidone predicts that most drugs have a rather low solubility in poly(vinylpyrrolidone). Conclusions  Miscibility of various drugs with polymers can be explored by coupling solution theories with experimental data. These approximations provide insight into the physical stability of drug–polymer mixtures and the thermodynamic driving force for crystallization.     

苦瓜蛋白提取工艺的研究

目的优选苦瓜蛋白提取工艺。方法考察乙醇浓度、温度、加氯化钠的量三因素对结果的影响,用L9(34)正交表优选提取工艺。结果影响苦瓜蛋白结晶得率的主要因素依次是加入氯化钠的倍数,温度及乙醇浓度,最佳工艺为A3B1C3。结论确定最佳工艺为:在19℃下,用95%的乙醇,加0.05倍氯化钠所得的结晶得率最高。     

A new approach to the diagnosis of children’s urolithiasis based on the Bonn Risk Index

Published data on the association between calcium oxalate (CaOx) crystallization and kidney stone disease in children are scarce. The aims of this study were to determine CaOx crystallization using the Bonn Risk Index (BRI) in children with urolithiasis in comparison to healthy controls, to evaluate the relationships between BRI and urinary parameters, such as pH, calciuria, oxaluria and citraturia, and to assess the association between BRI and the size of renal stones. We compared the BRI in 142 Caucasian children and adolescents (76 girls, 66 boys) aged 3-18 years with kidney stones and 210 healthy age- and sex-matched controls without urolithiasis. Urinary ionized calcium ([Ca2+]) was measured using a selective electrode, while the onset of spontaneous crystallization was determined using a photometer and titration with 40 mmol/L ammonium oxalate (Ox2-). The calculation of the BRI value was based on the Ca2+:Ox2- ratio. High-resolution renal ultrasonography was carried out to estimate the size of the renal stones. The BRI values were 15-fold higher in children with renal stones than in healthy children without stones. The same trend was shown by BRI/kg body weight (tenfold greater in children with renal stones than in healthy children without stones), BRI/per 1.73 m2 body surface (13-fold greater) and BRI/body mass index (23-fold greater). No association was observed between BRI and the diameter of stones. Children with kidney stones, both males and females, had an increased BRI compared with subjects without urolithiasis. High BRI suggests an association with lower urinary pH, hypercalciuria, hyperoxaluria or hypocitraturia, which are all risk factors of kidney stones. An increased BRI in children, although unrelated to renal stone size, reflects the risk of calcium oxalate crystallization and may indicate early metabolic disorders leading to urolithiasis.     

In vitro effect of lemon and orange juices on calcium oxalate crystallization

Aim  In recent years significant progress has been made in identifying and quantitating physico-chemical processes involved in urinary stone formation. The ability of urine to inhibit calcium oxalate crystallization is an important mechanism against stone formation. Dietary factors appear to affect the ability of urine to inhibit calcium oxalate crystallization. These factors encouraged us to study the effects of lemon and orange juices on calcium oxalate crystallization in vitro. Material and methods  The nucleation and aggregation of calcium oxalate monohydrate crystals were studied using turbidimetric 30-min time course measurements of optic density at 620 nm after mixing solutions containing calcium chloride and sodium oxalate at 37°C, pH 5.7. The formation of crystals is induced by the addition of the oxalate and calcium solution. The effects on calcium oxalate crystal growth of trisodium citrate, lemon and orange juices were examined. The effects of lemon and orange juices were evaluated by the addition of 50 ml of juices. The optical density is measured at physiological conditions. The maximum increase of optic density with time, termed S_N, reflects maximum rate of formation of new particles. After an equilibrium has been reached, a progressive decrease of optic density with time is observed. Rate of aggregation, S_A, is derived from the maximum decrease in optic density. Results  Among the modifiers studied, citrate decreased both S_N and S_A (P < 0.001). Lemon juice was also found to inhibit the rate of crystal nucleation and aggregation. But orange juice did not have any effect on the calcium oxalate crystallization (P > 0.05). Conclusion  These results show that effective prevention of urinary stone formation should aim at restoring the urine’s ability to inhibit calcium oxalate crystallization and more emphasis should be given to dietary measures.     

7-氨基头孢霉烷酸工艺研制

实验在头孢锌盐硅烷化过程中，加入了促溶剂N，N-二甲基甲酰胺，使反应周期缩短，两相反应更加充分，脱色过程采用混合炭法，增强了脱色效果。降低了7-ACA色级，从而使7-ACA质量得到了较大幅度的提高。     

Non-Isothermal Kinetic Analysis of the Crystallization of Metallic Glasses Using the Master Curve Method

The non-isothermal transformation rate curves of metallic glasses are analyzed with the Master Curve method grounded in the Kolmogorov-Johnson-Mehl-Avrami theory. The method is applied to the study of two different metallic glasses determining the activation energy of the transformation and the experimental kinetic function that is analyzed using Avrami kinetics. The analysis of the crystallization of Cu₄₇Ti₃₃Zr₁₁Ni₈Si₁ metallic glassy powders gives E_a = 3.8 eV, in good agreement with the calculation by other methods, and a transformation initiated by an accelerating nucleation and diffusion-controlled growth. The other studied alloy is a Nanoperm-type Fe₇₇Nb₇B₁₅Cu₁ metallic glass with a primary crystallization of bcc-Fe. An activation energy of E_a = 5.7 eV is obtained from the Master Curve analysis. It is shown that the use of Avrami kinetics is not able to explain the crystallization mechanisms in this alloy giving an Avrami exponent of n = 1.     

Effects of chondroitin sulphate,human serum albumin and Tamm-Horsfall mucoprotein on calcium oxalate crystallization in undiluted human urine

Summary The effects of physiological concentrations of chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein on the crystallization of calcium oxalate in undiluted, ultrafiltered human urine were investigated using particle size analysis and scanning electron microscopy. Neither the amount of oxalate required to induce detectable calcium oxalate crystal nucleation nor crystal morphology was affected by the presence of any of these macromolecules. Chondroitin sulphate had no effect on the amount of crystalline material deposited or on the size of the particles precipitated in response to a standard oxalate load. Human serum albumin slightly reduced the size of the crystal aggregates and caused a small increase in the amount of crystal matter precipitated. By contrast, Tamm-Horsfall mucoprotein significantly inhibited crystal aggregation and markedly increased the volume of matter deposited, although this could not be attributed to a promotion of solute precipitation. It was concluded that chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein cannot account for the inhibitory effects of macromolecules with a relative mass greater than 10 kDa in spun and filtered urine. Nonetheless, Tamm-Horsfall mucoprotein is likely to inhibit crystal aggregation in whole urine in vivo and may therefore be instrumental in preventing calcium oxalate stone formation.     

超临界状态下压力对穿心莲内酯萃取结晶的影响

目的 利用超临界CO2萃取结晶技术纯化穿心莲内酯。方法 采用系统观察法考察了超临界CO2萃取结晶分离对穿心莲内酯晶体形态、纯度、结晶量的影响，并采用扫描电镜、HPLC法分析结果。结果 穿心莲内酯晶体形态随压力的升高而变细、变短；随着压力的升高，晶体纯度提高，结晶量增加。结论 超临界CO2能萃取并同步高效结晶分离穿心莲内酯，为开发高质量中药活性成分提供一条捷径。     

液相化学沉积法制备云母钛珠光颜料

将液相化学沉积法合成云母钛珠光颜料剖析为Ｔｉ＾４＋的水解和水解产物在云母表面沉积两个过程。从Ｔｉ＾４＋的水解机理和结晶动力学两方面分析了影响云母钛合成的主要因素：反应体系的ｐＨ值，温度和Ｔｉ＾４＋浓度。对各主要因素进行了实验考察，得到了合成云母钛的较佳工艺条件，即反应体系的ｐＨ值为２．０￣２．２，反应温度为７５￣８０℃，Ｔｉ＾４＋浓度为３．１ｃ ｇ ／ｌ。同时对ＴｉＯ２在云母表面的沉积机理进行了探     

PET伸直链结晶体的研究进展

对聚对苯二甲酸乙二醇酯（PET）在特定的结晶条件下是否生成伸直链晶体进行了论证，系统总结了伸直链晶体形成的证据，并讨论了PET伸直链晶体形成的机理。