Influence of Glass Forming Ability on the Physical Stability of Supersaturated Amorphous Solid Dispersions

In this study, the influence of the glass-forming ability (GFA) of a drug on its physical stability in a supersaturated solid dispersion was investigated. Nine drugs were classified according to their GFA using their respective critical cooling rate. Their respective solubility in poly(vinylpyrrolidone-co-vinyl acetate) 6:4 (PVPVA64) was predicted using the melting point depression method based on the Flory-Huggins lattice theory. Supersaturated amorphous solid dispersions at a level of 25% w/w drug above saturation solubility in the polymer were prepared by film-casting, and their respective physical stability at temperatures of 10°C or 20°C above or below their respective T_g (dry conditions) was monitored by the use of polarized light microscopy. This study showed that drugs with good GFA (class 3) on average have higher physical stability in supersaturated amorphous solid dispersion compared to drug with modest GFA (class 2), which in turn have higher physical stability in supersaturated amorphous solid dispersion than drugs with poor GFA (class 1). These results indicate that the GFA of a drug and its physical stability in a supersaturated amorphous solid dispersion stored at a temperature above or below its T_g are correlated.     

氧化钾的含量对牙科微晶玻璃析晶性能的影响

目的 研究氧化钾（K2O）的含量对牙科微晶玻璃析晶性能的影响。方法 在Li2O-SiO2-Al2O3-P2O5-ZnO体系的基质玻璃中添加不同含量的K2O，根据差热分析（DTA）曲线确定微晶玻璃的热处理制度，采用X射线衍射分析和扫描电子显微镜（SEM）观测来比较不同的K2O含量对牙科Li2O-SiO2-Al2O3-P2O5-ZnO体系微晶玻璃析晶成分和显微结构的影响。结果 K2O的引入有助于降低玻璃基体的粘度，促进基质玻璃的析晶。在基质玻璃中添加5.3 wt%的K2O可以使玻璃在热处理后析出较多的二硅酸锂晶体，晶体呈板条状，长度约为4 μm，在玻璃基质中分布均匀。 结论 添加一定量的K2O有助于提高牙科Li2O-SiO2-Al2O3-P2O5-ZnO体系微晶玻璃的析晶性能。     

Crystallization/Melting Kinetics and Morphological Analysis of Polyphenylene Sulfide

Crystallization and melting kinetics of polyphenylene sulfide (PPS) are determined using fast scanning calorimetry. The temperature dependence of half‐time crystallization of isothermally melt‐crystallized PPS shows a downward convex curve with a minimum at 160 °C. The minimum crystallization half‐time is about 3 s. The analysis of heating rate dependence of the melting temperature reveals a zero‐entropy‐production melting temperature of the sample. The microstructure of the sample, which is prepared by fast scanning calorimetry, is investigated by small‐angle X‐ray scattering and polarizing optical microscopy. The crystallinity and lamellar thickness of the sample annealed for 400 s decrease with decreasing crystallization temperature. The size of spherulites becomes small as the isothermal temperature is decreased. Transcrystalline morphology is observed near the surface between the sample and nitrogen gas at a crystallization temperature of 120 °C. The thickness of the transcrystalline layer disappears as the isothermal temperature is increased.     

Mathematical Modeling of Crystallization Elution Fractionation of Ethylene/1‐Octene Copolymers

Crystallization elution fractionation (CEF) is a relatively new polyolefin characterization technique used to estimate the chemical composition distribution (CCD) of semicrystalline copolymers. CEF is developed to enhance the resolution and reduce the analysis time of temperature rising elution fractionation (TREF) by separating polymer samples in both the crystallization and elution steps. A model based on the concept of population balance, crystallization/dissolution kinetics, and dispersion model is developed to understand the CEF fractionation mechanisms. The proposed CEF model is found to describe well the experimental CEF profiles of a series of ethylene/1‐octene copolymers with different comonomer contents.

     

IPP在草酸钙结晶评分中应用的可行性研究

目的探究IPP图像分析软件评估结晶情况可行性、可靠性和稳定性。方法由两位研究员分别对同一批草酸钙结晶照片进行人工评分和应用IPP评分,通过统计学方法检验评分的一致性;1周后,一位研究员再次进行人工评分和应用IPP评分,通过统计学方法检验自身前后评分的一致性。结果人工评分草酸钙结晶,两位研究员及同一研究员前后所给的评分,其一致性均差;应用IPP评分,两位研究员及同一研究员前后所给的评分,其一致性均较高。结论应用IPP图像分析软件对草酸钙结晶情况进行评分具有可靠性和稳定性。     

Population Balance Model for Simulation of the Supersaturation–Precipitation Behavior of Drugs in Supersaturable Solid Forms

We developed a simulation method to describe in vitro drug concentration?time profiles under supersaturated conditions. In a nonsink dissolution test of carbamazepine polymorphic form III (CBZ_III), a model supersaturable solid, the concentration of carbamazepine reached a supersaturated state against its dihydrate form (CBZ_DH). After a certain period, de-supersaturation due to the precipitation of CBZ_DH was observed. In the simulation of this typical dissolution?precipitation profile, the precipitation process of CBZ_DH was simulated by a population balance model in which the rates of primary/secondary nucleation and growth of CBZ_DH were considered. Six rate constants in the precipitation model were determined from de-supersaturation profiles in unseeded isothermal crystallization experiments of CBZ_DH. The dissolution process of CBZ_III was modeled on the basis of its dissolution profile under a sink condition. The simulated concentration versus time curves satisfactorily reproduced the characteristics of dissolution, supersaturation, and precipitation behavior of the model drug. The presented method will enable rational design of formulations and accurate prediction of the oral absorbability of drugs in supersaturable solid forms.     

Characterization of recrystallized itraconazole prepared by cooling and anti-solvent crystallization

The objective of the present study was to alter the crystal habit of itraconazole (ITZ) by cooling and anti-solvent crystallization and characterize its properties. ITZ was recrystallized in different solvents and the effects of each solvent on morphology of crystals, dissolution behavior and solid state of recrystallized drug particles were investigated. The results revealed that ITZ crystals recrystallized by cooling and anti-solvent crystallization showed the different crystal habits from the untreated ITZ. Using cooling crystallization tended to provide needle-shaped crystals while the crystals obtained from anti-solvent crystallization showed more flaky, plate shape. This indicated the importance of preparation method on nucleation and crystal growth. No change in drug polymorphism was observed, according to determination of thermal property and crystalline state by differential scanning calorimetry and powder X-ray diffractometry, respectively. The recrystallized ITZ showed higher drug dissolution than untreated ITZ and the highest drug dissolution was observed from the samples recrystallized in the presence of PEG 200, which provided the small plate-shaped crystals with tremendously increased in surface area. However, the increasing of drug dissolution is relatively small, therefore, further development may be required.     

高纯度庆大霉素C1a游离碱制备工艺研究

目的 探索用大孔吸附树脂层析法及盐析结晶法精制纯化硫酸依替米星起始物料-庆大霉素C1a成品(HPLC纯度91%~93%)，从而减少由起始物料引入依替米星杂质的水平。方法 以庆大霉素C1a吸附量和庆大霉素C1a纯度为指标，考察大孔吸附树脂纯化庆大霉素C1a的吸附性能和洗脱参数；以盐析后庆大霉素C1a样品纯度和盐析收率为指标，考察盐析工艺最佳温度、溶剂、酸的添加量及酸的种类。结果 获得较优的树脂NM200，获得较优的解析液pH值为2.0和流速0.5BV/h。经过优化后，纯化收率从65%提高至74%。通过盐析结晶条件筛选和优化，确定室温先加溶剂后加硫酸(pH6.5)和甲醇与乙醇1:2的条件较优，优化后获得的庆大霉素C1a纯度达到98.2%，收率大于93%。研究了多种无机酸盐析结晶的情况，发现磷酸、硫酸和碳酸条件下能析出白色固体。结论 通过比较大孔吸附树脂和盐析结晶的纯化连接，组合纯化后获得的庆大霉素C1a游离碱纯度大于99.0%，比纯化前样品提高6%以上，收率大于70%。     

The Synthesis of α-MoO3 by Ethylene Glycol

This study investigated the use of ethylene glycol to form α-MoO₃ (molybdenum trioxide) from ammonium molybdate tetrahydrate at various sintering temperatures for 1 h. During the sintering process, the morphologies of the constituents were observed using scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy was used to explain the reaction process. In this work, the results obtained using X-ray photoelectron spectroscopy (XRD) demonstrated that, when the molybdenum trioxide powder was treated thermally at 300 °C, the material exhibited crystallinity. The peaks were indexed to correspond with the (110), (040), (021), (111), and (060) crystallographic planes, and the lattice parameters of a, b, and c were about 3.961, 13.876, and 3.969 Å. Using these observations, we confirmed that orthorhombic α-MoO₃ was formed for sintering temperatures from 300 to 700 °C. Pattern images were obtained by the selected area electron diffraction pattern (SAED) technique, and the d distance of the high resolution transmission electron microscopy (HRTEM) images were almost 0.39 and 0.36 nm, and the Mo 3d_5/2, Mo 3d_3/2, and O 1s of X-ray photoelectron spectroscopy (XPS) were located at 233.76, 237.03, and 532.19 eV, which also demonstrated that α-MoO₃ powder had been synthesized.