制药企业清洁生产研究——以扬州制药厂为例

通过对清洁生产审核一般规律的研究,介绍扬州制药厂清洁生产审核实践之案例。为实施清洁生产提出11条节水措施,5种节电方案,生产过程中9个控制要素,并对提供动力、能源以及仓储等的生产辅助部门进行清洁生产审核。     

探讨EHS管理体系在制药企业中的运用

介绍了现代先进的企业管理工具——EHS管理体系,阐述了我国制药企业EHS现状,分析与国外同行的差距,探讨在我国制药企业中的具体运用并作了前景展望。     

肾移植术后的临床药学监护实践

目的提高肾移植术后患者药物治疗效果,降低术后不良反应。方法加强血药浓度监测,调整用药剂量和品种,为患者建立药历,开展用药指导。结果与结论通过实施药学监护有效降低了肾移植术后药物不良反应发生率。     

Application of the Repeated Measures (Split-Plot) Design to the Development of Processes for Drug Substances

A case study from the chemical and pharmaceutical industries is used to show the value of the repeated measures design in developing processes for drug substances. This article advocates the use of the repeated measures design in situations that commonly arise in the chemical and pharmaceutical industries when repeated measurements are taken on the same experimental unit, instead of the common practice of comparing only individual conditions, a procedure that is inappropriate in many cases. One of the most important advantages of applying the repeated measures design is the abundance of data that can be obtained by taking into account the entire response curve instead of only isolated individual points on it.     

浅谈制药工程专业英语词汇教学

制药工程专业英语的教学对新型制药专业人才的培养具有重要意义,而专业词汇又是教学中的一项重点和难点。文章针对专业词汇的特点,结合笔者近几年教学的经验与体会,探讨了制药工程专业英语词汇的教学方法与策略,以增强制药工程专业英语的教学效果,提高学习效率。     

Pharmaceutical and personal care products in tile drainage following surface spreading and injection of dewatered municipal biosolids to an agricultural field

Land application of municipal biosolids can be a source of environmental contamination by pharmaceutical and personal care products (PPCPs). This study examined PPCP concentrations/temporally discrete mass loads in agricultural tile drainage systems where two applications of biosolids had previously taken place. The field plots received liquid municipal biosolids (LMB) in the fall of 2005 at an application rate of ∼ 93,500 L ha^− 1, and a second land application was conducted using dewatered municipal biosolids (DMB) applied at a rate of ∼ 8 Mt dw ha^− 1 in the summer of 2006. The DMB land application treatments consisted of direct injection (DI) of the DMB beneath the soil surface at a nominal depth of ∼ 0.11 m, and surface spreading (SS) plus subsequent tillage incorporation of DMB in the topsoil (∼ 0.10 m depth). The PPCPs examined included eight pharmaceuticals (acetaminophen, fluoxetine, ibuprofen, gemfibrozil, naproxen, carbamazepine, atenolol, sulfamethoxazole), the nicotine metabolite cotinine, and two antibacterial personal care products triclosan and triclocarban. Residues of naproxen, cotinine, atenolol and triclosan originating from the fall 2005 LMB application were detected in tile water nearly nine months after application (triclocarban was not measured in 2005). There were no significant differences (p > 0.05) in PPCP mass loads among the two DMB land application treatments (i.e., SS vs. DI); although, average PPCP mass loads late in the study season (> 100 days after application) were consistently higher for the DI treatment relative to the SS treatment. While the concentration of triclosan (∼ 14,000 ng g^− 1 dw) in DMB was about twice that of triclocarban (∼ 8000 ng g^− 1 dw), the average tile water concentrations for triclosan were much higher (43 ± 5 ng L^− 1) than they were for triclocarban (0.73 ± 0.14 ng L^− 1). Triclosan concentrations (maximum observed in 2006 ∼ 235 ng L^− 1) in tile water resulting from land applications may warrant attention from a toxicological perspective.     

伊普黄酮合成新工艺

以间苯二酚和苯乙酸为基本原料,"一锅煮"合成中间体7-羟基异黄酮,然后再与2-溴丙烷醚化生成目标产物,目标产物结构经光谱确证为伊普黄酮,总收率这90%,纯度达98%以上.新工艺具有反应条件温和、操作简便、收率高和成本低等特点,更适合于工业化生产.     

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.     

Design of experiments (DoE) in pharmaceutical development

At the beginning of the twentieth century, Sir Ronald Fisher introduced the concept of applying statistical analysis during the planning stages of research rather than at the end of experimentation. When statistical thinking is applied from the design phase, it enables to build quality into the product, by adopting Deming’s profound knowledge approach, comprising system thinking, variation understanding, theory of knowledge, and psychology.

The pharmaceutical industry was late in adopting these paradigms, compared to other sectors. It heavily focused on blockbuster drugs, while formulation development was mainly performed by One Factor At a Time (OFAT) studies, rather than implementing Quality by Design (QbD) and modern engineering-based manufacturing methodologies.

Among various mathematical modeling approaches, Design of Experiments (DoE) is extensively used for the implementation of QbD in both research and industrial settings. In QbD, product and process understanding is the key enabler of assuring quality in the final product. Knowledge is achieved by establishing models correlating the inputs with the outputs of the process. The mathematical relationships of the Critical Process Parameters (CPPs) and Material Attributes (CMAs) with the Critical Quality Attributes (CQAs) define the design space. Consequently, process understanding is well assured and rationally leads to a final product meeting the Quality Target Product Profile (QTPP).

This review illustrates the principles of quality theory through the work of major contributors, the evolution of the QbD approach and the statistical toolset for its implementation. As such, DoE is presented in detail since it represents the first choice for rational pharmaceutical development.