Pellet layering: scale-up considerations using different kinds of processing equipment

Objective: In this study an aqueous suspension of poorly water-soluble HCT (hydrochlorothiazide) was layered on small spherical starter cores with a drug content in the final pellets of 30%. The aim was to compare different kinds of processing equipment (Wurster fluid-bed, CPS rotor fluid-bed and drum coater) in view of process efficiency, process duration and feasibility to scale-up.

Results: In a pilot scale drum coater, it was possible to achieve the desired LE (layering efficiency) and yield specifications (both >95%), but the process duration was at least 202?min. In the small scale Wurster fluid-bed machine, it was possible to reduce the process time for an optimized process from 67?min to 41?min. However, the acceleration of the process led to an increase of agglomerates and the same process took at least 114?min in the scale-up experiments. A small scale CPS rotor processor with a cone-shaped disc was superior to the conventional planar rotor disc design, regarding yield and agglomerates. This rotor process was both, fast and highly efficient (yield: 98.4%; LE: 99.3%). The high quality of the process was also observed for the pilot scale batches, in which neither considerable losses of drug (LE ≥ 98.6%) nor formation of agglomerates occurred. The absolute spray rate in this pilot scale process was 85?kg/h.

Conclusion: Best results were achieved with the CPS rotor technology. With a duration of 29?min (small scale) and 44?min (pilot scale) it was the fastest option to produce layered pellets.     

固液非均相硝化器内流体流动模型的研究

本文以火炸药生产中常用的固液非均相硝化器为模拟对象,建立并检验了该系统停留时间分布(RTD)的流动模型。在五个几何相似的模拟硝化器(碟底釜,体积为0.005～0.150m~3)内,研究了固液两相RTD的变化规律。研究结果为固液非均相硝化器的放大提供了理论和实验依据,具有较大的实际意义。     

碳纳米管:可控制备决定未来（英文）

在过去几十年中,碳纳米管由于其优异的物理和化学性质而备受关注,被认为是一个强有力的未来明星材料.尽管基于碳纳米管的诸多产品及应用实例相继浮现,但是碳纳米管所呈现出的实际性质与理论值之间依然存在较大差异,无法达到研究者的预期,这源自于目前尚未成熟的控制制备技术.碳纳米管的可控制备技术包括结构的精细控制方法和样品的宏量制备技术,这在很大程度上决定了碳纳米管的未来发展前景.基于此,本文概述了近几十年来研究者们在碳纳米管的精细结构控制、聚合状态设计和样品宏量制备等方面的主要进展,进一步指出了碳纳米管未来的可控制备技术必须与特定化的应用紧密结合,以迎接即将来临的产业化时代.     

城镇污水磁种絮凝-高梯度磁分离处理扩大连续试验研究

在小试研究基础上, 开展了磁种絮凝-高梯度磁分离净化处理城镇污水的扩大连续试验研究。试验结果表明, 该工艺对去除城镇污水中的磷、重金属有特效, 并能同时去除其中的COD_Cr、BOD₅、SS, 出水水质达到或接近国家一级排放标准, 是一种很有发展前途的工艺, 尤其适用于城市小区、小城镇污水处理厂建设、城市大中型污水处理厂增能扩容及出水回用强化处理。     

聚氯乙烯树脂高效组合式干燥工艺数值模拟及工程放大

聚氯乙烯树脂生产装置的具体特点,依据聚氯乙烯树脂的干燥动力学数据,数值模拟了聚氯乙烯高昴组合式旋流干燥装置,经与２．５万ｔ／ａ生产装置对比后发现：数值模拟结果与工厂实测数值基本吻合,说明所建立的数学模型可以较地模拟聚氯乙烯高效组合式旋流干燥装置,同时,以此为基础,设计开发了５万ｔ／ａ生产装置。     

Production of fine lactose particles from organic solvent in laboratory and commercial-scale spray dryers

A laboratory spray dryer and a commercial dryer with a production rate 50 times greater, both using two-fluid nozzles, were used to dry the same formulation from organic solvent. Both dryers generated particles of similar size, with tight particle size distributions (span <2), which varied with atomization gas flow rate, liquid flow rate, and solids concentration. Small-scale results with an external mixing nozzle were fitted to a correlation based on literature recommendations. This also fitted well for the commercial dryer with external mixing, and an internal mixing nozzle gave a tighter size distribution. Hence, successful verification at scale has been achieved.     

A quality by design approach to scale-up of high-shear wet granulation process

High-shear wet granulation is a complex process that in turn makes scale-up a challenging task. Scale-up of high-shear wet granulation process has been studied extensively in the past with various different methodologies being proposed in the literature. This review article discusses existing scale-up principles and categorizes the various approaches into two main scale-up strategies – parameter-based and attribute-based. With the advent of quality by design (QbD) principle in drug product development process, an increased emphasis toward the latter approach may be needed to ensure product robustness. In practice, a combination of both scale-up strategies is often utilized. In a QbD paradigm, there is also a need for an increased fundamental and mechanistic understanding of the process. This can be achieved either by increased experimentation that comes at higher costs, or by using modeling techniques, that are also discussed as part of this review.     

A heat transfer model and supporting experiments to guide the uniform gelation of molecular oleogels during scale-up

The quest for novel vegetable oil structuring strategies has been progressing since the discovery of the deleterious impacts of trans fats. Although oleogelation using bioderived molecular gelators has been proven to be successful as an alternative to traditional hydrogenation methods, efforts are needed to meet the industrial requirements. A major constraint during the fabrication of oleogels is to achieve consistency in physical properties during scale-up. Experiments showed that gelation fails to occur when larger volumes were prepared based on the minimum gelation concentration (MGC) of gelators, determined using the smallest oil volume (1 ml), a general laboratory practice. This observation was consistent with all the molecular gelators used in this study; sorbitol dioctanoate, mannitol dioctanoate, and 12-hydroxystearic acid. To understand this behavior, a mathematical model was developed since gelator network propagation is governed by the cooling rate. The model indicates that maintenance of a minimal thermal gradient via uniform heat dissipation and gelation time is necessary to achieve homogeneous gel propagation across the vial. With these predictions, we hypothesized and confirmed that oleogels with constant surface area-to-volume ratio could result in identical gelation times and consistent physical properties (MGC, melting temperature, melting enthalpy, yield stress, solid phase content, and oil binding capacity) during scale-up.     

工业反应过程的开发方法Ⅺ．炔醛法合成丁二醇反应过程的开发

以炔醛法合成１，４一丁二醇反应的炔化反应过程和加氢反应过程为研究对象，应用工业反应过程开发方法的基本原则，进行炔化反应和加氢反应开发方法的论述，包括确定优选工艺条件、反应器型大的选择和反应器的主要工程问题。从小试、中试、冷漠试验到工业规模试验，为大型装置设计提供依据。