Effect of pharmaceutical agent degradation on axonal transport drug delivery: An analytical solution for a transient situation

This paper is motivated by recent experimental research that demonstrated pharmacological efficiency of axonal transport drug delivery. The purpose is to develop a model of this process and to study how the rate of destruction of pharmaceutical agent complexes (PACs) affects their transport in the axon. The model includes two populations of PACs: PACs in the state when they are driven retrogradely (from the axon terminal toward the neuron soma) by dynein motors and PACs residing in the accumulated state (but can still be re-released to the dynein-driven state). The coupling between the kinetic states is accounted for by first-order reactions. Utilizing Laplace transform, analytical solutions for concentrations of these two populations of PACs are obtained. The effect of PAC destruction is investigated for different values of other parameters. It is shown that the shapes of the waves describing the PAC concentrations can be significantly affected by transport parameters.     

湿式氧化法预处理高浓度合成制药废水的研究

以高浓度化学合成制药废水为研究对象,考察了湿式氧化法预处理对COD去除率的影响规律,并考察了均相催化剂的催化效果。结果表明,均相催化剂的添加能够大幅度提高COD的去除率,对于进水COD为30 000 mg/L的废水,在湿式氧化法预处理过程中添加硫酸铜能够使COD去除率从54.6%提高到76.5%以上。     

催化湿式氧化法处理制药污泥的实验研究

以硝酸铜作为催化剂,应用催化湿式氧化法处理制药污泥,研究该方法对COD和VS的去除效果.结果表明,添加催化剂能有效提高湿式氧化法的处理效果,且在反应温度为260℃,搅拌转数为300 r/min,起始氧气压力为1.0 MPa,催化剂添加量为0.5 g/L,反应时间为60 min的条件下,污泥VS和COD的去除率分别可达到...     

Form selection of concomitant polymorphs: A case study informed by crystallization kinetics modeling

Molecular mechanisms and process kinetics of crystallizing concomitant polymorphs remain poorly understood. Solvent-mediated phase transformation and concomitant crystallization are difficult to be distinguished in practice, as multiple forms can be detected at the same time. Herein, we developed a population balance model to simulate a concomitant crystallization process of two polymorphs of tolfenamic acid. Our kinetic modeling aims to understand concomitant crystallization and help guide form selection of such a molecular system. Crystallization kinetics of ethanolic solutions were uncovered from induction time measurements, as well as seeded and unseeded crystallization experiments. Experimental and simulation results demonstrate that the stable form I crystallizes concomitantly with the metastable form II. The faster growing form II results in an intermediate decline in the composition of form I in crystallized samples, a characteristic feature of the concomitantly crystallized system. A four-quadrant scheme of attainable polymorph outcome was simulated under various crystallization conditions.     

Quality-by-control of intensified continuous filtration-drying of active pharmaceutical ingredients

Continuous manufacturing and closed-loop quality control are emerging technologies that are pivotal for next-generation pharmaceutical modernization. We develop a process control framework for a continuous carousel for integrated filtration-drying of crystallization slurries. The proposed control system includes model-based monitoring and control routines, such as state estimation and real-time optimization, implemented in a hierarchical, three-layer quality-by-control (QbC) framework. We implement the control system in ContCarSim, a publicly available carousel simulator. We benchmark the proposed control system against simpler methods, comprising a reduced subset of the elements of the overall control system, and against open-loop operation (the current standard in pharmaceutical manufacturing). The proposed control system demonstrates superior performance in terms of higher consistency in product quality and increased productivity, proving the benefits of closed-loop control and of model-based techniques in pharmaceutical manufacturing. This study represents a step forward toward end-to-end continuous pharmaceutical processing, and in the evolution of quality-by-design toward quality-by-control.     

Co-crystallization for enhanced dissolution rate of bicalutamide: preparation and evaluation of rapidly disintegrating tablets

Objectives: Enhance the dissolution rate of bicalutamide via co-crystallization with sucralose (sweetener), with the aim to develop rapidly disintegrating tablets with subsequent prompt dissolution.

Significance: Bicalutamide is antiandrogenic agent for the treatment of prostate cancer but has low and variable oral bioavailability, mainly attributed to poor dissolution. Co-crystallization with benign excipients is promising for dissolution enhancement with the additive serving dual functions. The benefit will become greater if dissolution enhancement is associated with the development of orodispersible tablets which is suitable for elderly patients who are the most vulnerable for prostate cancer.

Methods: Bicalutamide was dissolved in acetone in the presence of increasing molar ratios of sucralose. The solvent was evaporated while mixing to deposit crystals that were subjected to wet co-grinding until drying. The developed solids were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and X-ray diffraction in addition to monitoring bicalutamide dissolution.

Results: Instrumental analysis provided evidences for co-crystallization which was initiated at 1:1 molar ratio of bicalutamide to sucralose with complete co-crystallization at 1:4 molar ratio. The co-crystals provided faster bicalutamide dissolution compared with the unprocessed drug and that recrystalized from acetone in the absence of sucralose. The formulation containing bicalutamide with sucralose at 1:4 molar ratio was selected for tablet formulation into which superdisintegrants were included. The developed tablets exhibited flash disintegration with subsequent fast dissolution of bicalutamide.

Conclusions: The study introduced co-crystallization of bicalutamide with sucralose as an efficient tool to enhance the dissolution rate and to develop rapidly dissolving tablets for intraoral administration.     

多级A/O+生物脱氮技术处理高浓度制药废水

介绍了多级A/O+生物脱氮技术在高浓度制药废水处理工程中的应用。实际工程运行结果表明,处理出水pH值为6～9、COD≤500 mg/L、SS≤400 mg/L、氨氮≤35 mg/L、TN≤70mg/L、TP≤8 mg/L,符合《污水综合排放标准》(GB 8978—1996)的三级标准,其中总氮、总磷达到《污水排入城镇下水道水质标准》(CJ 343—2010)的B级标准,氨氮达到《工业企业废水氮、磷污染物间接排放限值》(DB 33/887—2013)要求。该工程采用的点对点水解布水、生物脱氮、磁悬浮风机等新型技术和设备,具有较好的推广应用价值。     

水环境中药物污染、检测及去除研究进展

分析国内外水体中药物污染现状及其差异,详述水环境中痕量药物残留分析典型流程及固相萃取结合色谱 质谱联用的检测方法,总结污水处理厂、传统氧化工艺、高级氧化工艺、活性炭吸附和新型水处理技术去除效果和机理,认为在我国对各类水体进行药物污染调查、明确"优先污染药物"及研究水处理工艺药物去除效果等方面是今后研究的重点。     

中药废水处理研究进展

综述了目前中药工业废水处理中应用的各种物化、生物处理技术；并对各种处理方法的应用特点进行了论述。最后指出了中药工业废水处理技术今后研究开发的方向和思路。