The control of paracetamol particle size and surface morphology through crystallisation in a spray dryer

The parameters governing the crystallisation of paracetamol using various conventional techniques has been extensively studied, however the factors influencing the drug crystallisation using spray drying is not as well understood. The aim of this work was to investigate the crystallisation of an active pharmaceutical ingredient through evaporative crystallisation using a spray dryer to study the physicochemical properties of the drug and to use semi-empirical equations to gain insight into the morphology and particle size of the dried powder. Paracetamol solutions were spray dried at various inlet temperatures ranging from 60 °C to 120 °C and also from a series of inlet feed solvent compositions ranging from 50/50% v/v ethanol/water to 100% ethanol and solid-state characterisation was done. The size and morphology of the dried materials were altered with a change in spray drying parameters, with an increase in inlet temperature leading to an increase in particle Sauter mean diameter (from 3.0 to 4.4 µm) and a decrease in the particle size with an increase in ethanol concentration in the feed (from 4.6 to 4.4 µm) as a result of changes in particle density and atomised droplet size. The morphology of the dried particles consisted of agglomerates of individual crystallites bound together into larger semi-spherical agglomerates with a higher tendency for particles having crystalline ridges to form at higher ethanol concentrations of the feed.     

The incorporation of low-substituted hydroxypropyl cellulose into solid dispersion systems

While the use of amorphous solid dispersions to improve aqueous solubility is well documented, little consideration has traditionally been given to the finished dosage form. The objective of this study was to evaluate the dissolution performance of amorphous solid dispersions containing a dispersed superdisintegrant with binding properties. KinetiSol® dispersing was used to thermally process hypromellose acetate succinate-based compositions containing the drug substance nifedipine (NIF) and a highly compressible grade of low-substituted hydroxypropyl cellulose (New Binder Disintegrants; NBD-grade). Solid-state analysis demonstrated that compositions were rendered amorphous during processing. Tablets containing intra-dispersion NBD were found to exhibit non-sink dissolution performance similar to milled intermediate, demonstrating excellent disintegration characteristics. Conversely, tablets without intra-dispersion NBD were found to release significantly less NIF during dissolution analysis due to particle agglomeration. It was determined that compressibility and particle wetting increased as the level of intra-dispersion NBD increased.     

湿法磷酸萃取工艺对磷石膏晶形的影响

采用模拟湿法磷酸生产方式,通过控制萃取反应工艺条件来控制磷石膏晶形.采用扫描电子显微镜观察晶体形貌,采用激光粒度分析仪测定粒度分布和平均粒径.结果表明:液相中游离的H2SO4含量和P2O5含量对磷石膏的晶体形貌和大小都有影响,前者提高,二水石膏析晶过饱和度降低,磷石膏晶体由薄片状变为粗大的柱状和斜方六面晶体,然后再向聚晶转变,平均粒径变大;后者提高,二水石膏析晶过饱和度升高,晶体由粗大的板状变为柱状,然后再向细针状转变,平均粒径变小.反应温度升高,二水石膏析晶过饱和度降低,晶体尺寸变大,但晶体形状基本不变,均为柱状.从兼顾湿法磷酸生产和磷石膏建材资源化的角度出发,提出优化的萃取反应工艺条件为:液相游离H2SO4质量分数为5％,液相P2O5质量分数为15％～20％,反应温度为80℃,料浆液固比为2.5:1(质量比).     

Fe、Cr过饱和固溶量对Zr-4合金耐蚀性的影响

制备了4种Fe、Cr过饱和固溶量不同的Zr-4合金试样,采用透射电镜分析了4种试样的显微组织,并研究了4种试样在500℃/10.3 MPa和360℃/18.6 MPa/0.01mol/L LiOH水溶液中的腐蚀规律。结果表明:在Zr-4合金未发生疖状腐蚀的情况下,降低α-Zr中过饱和固溶的Fe、Cr含量有利于改善Zr-4合金在500℃/10.3 MPa蒸汽中的耐均匀腐蚀性能。提高α-Zr中过饱和固溶的Fe、Cr含量有利于改善Zr-4合金在LiOH水溶液中的耐均匀腐蚀性能。     

萃取净化磷酸制备磷酸二氢钠过程及结晶介稳特性

提出了以工业湿法磷酸和氢氧化钠为原料,以磷酸三丁酯(TBP)+煤油(稀释剂)作为萃取剂,通过萃取、反萃与结晶工艺相结合,制备磷酸二氢钠的一种新工艺过程.以完整工艺的实施为前提,结合必要的实验并确定合适的萃取温度、稀释剂加入量、反萃取条件等因素.与热法磷酸原料制备磷酸二氢钠相比,溶剂萃取磷酸中阴、阳离子质量分数的差异造成...     

铝酸钠溶液种分过程降温制度的研究

研究了铝酸钠溶液晶种分解过程中的相对过饱和度、分解率、产品粒度分布和反应速率常数在不同温度下的变化情况。结果表明,在50~75℃,铝酸钠溶液的相对过饱和度随温度的升高而逐渐减小,产品的平均粒度和反应速率常数随温度升高而增大,铝酸钠溶液种分分解率在65℃时达到最大。在降温制度下,铝酸钠溶液种分的分解率为28.86%,仅略低于65℃时的分解率,而产品粒度大于65℃时的产品粒度,降温制度下的铝酸钠溶液种分既能保证分解率又能提高产品氢氧化铝的粒度。     

35Cr3SiMnMoV钢超饱和渗碳研究

对自行研发的35Cr3SiMnMoV渗碳钢进行超饱和渗碳,并对渗层的组织、硬度及耐磨性能进行了研究。结果表明:试验钢经超饱和渗碳、淬火加低温回火后,超饱和渗碳层由回火马氏体、残留奥氏体和大量弥散分布的碳化物构成,硬度可达1025HV0.1,其耐磨性比20CrMnMo、20Cr2Ni4钢常规渗碳层提高了约60%。     

Kinetics of precipitation of surfactants. II. Anionic surfactant mixtures

Precipitation kinetics were measured for calcium-induced precipitation of mixtures of two anionic surfactants. The overall time required for precipitation to occur increased dramatically in specific ranges of compositions for the surfactant mixtures when compared to single components. Adsorption of the nonprecipitating surfactant onto the precipitate surface was shown to be responsible for this remarkable synergism. The higher the supersaturation of surfactant monomers, the more rapidly precipitation occurred. Under conditions where both surfactants were supersaturated, precipitation sometimes occurred in stepwise fashion, where crystals of different composition were formed with different induction times. Image analysis of the crystalline precipitate showed that crystal habit was affected when the two surfactants were mixed, indicating that processes such as adsorption and coprecipitation (most likely by inclusion) were occurring. When the crystals were allowed to age in solution for a period of 1 wk, the crystalline phase from the mixed surfactant solutions was found to separate into two types of crystals, which resembled week-old crystals formed from single surfactant systems.     

SIMULATIONS OF THE THREE-DIMENSIONAL TOTAL DISSOLVED GAS SATURATION DOWNSTREAM OF SPILLWAYS UNDER UNSTEADY CONDITIONS

Dams are often operated in a way to discharge over the spillways, which would cause a high dissolved concentration of air and be harmful to fish. The bubble transfer and the water surface transfer play an important role in affecting the concentration of the Total Dissolved Gas (TDG). Based on recent numerical simulations of the total dissolved gas saturation, in this article, a two-phase TDG transport equation is adopted to develop an unsteady three-dimensional (3-D) two-phase flow Computational Fluid Dynamics (CFD) model, including a number of parameters such as water depth, pressure and air volume entrained. This model is used to predict the hydrodynamics and the TDG distribution under unsteady discharge conditions. Good agreement between measured and numerical results is obtained for a case study.     

Evaluation of different screening methods to understand the dissolution behaviors of amorphous solid dispersions

Objective: The objectives of the current study were to understand the dissolution behaviors of amorphous solid dispersions (ASD) using different screening methods and their correlation to the dissolution of formulated products.

Materials and methods: A poorly soluble compound, compound E, was used as a model compound. ASDs were prepared with HPMC, Kollidon VA64 and Eudragit EPO using hot-melt extrusion. Different techniques including precipitation, powder, capsule and compact dissolution and the dissolution of formulated products were conducted in USP simulated gastric fluid using a USP II dissolution apparatus.

Results and discussions: It was found that a precipitation study could generally predict powder, capsule and compact dissolution. Yet, it was recommended to run the dissolution at a higher paddle speed or for a longer duration to improve the predictability. It was also recommended to run powder, capsule and compact dissolution at both slow and high speeds to gain insights into wetting, dispersion and the dissolution of a system. Sometimes, capsule or compact dissolution could not be predicted by precipitation or powder dissolution due to plug formation. In this case, properly designed dosage forms were needed to break up this plug to optimize the dissolution profiles. On the contrary, formulations and dissolution conditions would have minimal effects on the dissolution profiles of a fast-dissolving solid dispersion.

Conclusions: Different techniques are available to select the right polymers to optimize dissolution behaviors. However, it is important to understand the merits and limitations of each technique in order to optimize the formulations for amorphous solid dispersions.