Chemical Pharmaceutical Technology

Author: Ji Zhizhong / Editor-in-Chief: Ji Zhizhong
Publisher:
Publishing Date: 1998-01-01
Features:
Content Summary This book is a textbook for chemical pharmaceutical professional courses in higher education institutions. Chapters 1 to 6 cover general principles, including the design and selection of pharmaceutical process routes, process research for chemically synthesized drugs, pilot-scale scaling-up and production process procedures, as well as the prevention and treatment of "three wastes" in pharmaceutical factories. Chapters 7 to 11 discuss specific cases, using five drugs—sulfamethoxazole, hydrocortisone, norfloxacin, vitamin C, and chloramphenicol—as examples to introduce their production principles and process procedures. This book can be used as a teaching material for relevant majors in chemical engineering and pharmaceutical schools, and is also reference material for teachers, technicians engaged in chemical pharmaceutical production, research, and design.
Excerpt:
Foreign trade export volume increased 3.6 times; the number of enterprises grew 1-fold, and the original value of fixed assets increased 3 times (reaching 120 billion yuan) [9]. China has established nearly 20 pharmaceutical production enterprises abroad, and several multinational companies are in the process of being set up. This shows that China's chemical pharmaceutical industry, particularly in the production of raw materials, has already secured a certain position in the international market. Although China's pharmaceutical industry has developed significantly, it still cannot fully meet the needs of healthcare services, especially as some product qualities still lag behind those of economically developed countries and fail to reach the level of international products. The cycle for product renewal is long, especially for chemically synthesized raw materials, which are still primarily in the stage of imitation development; pharmaceutical formulation technology is relatively backward; production scale is small, and economic efficiency has not been fully realized. Traditional Chinese medicine (TCM) and modern medicine (referred to as Western medicine or primarily chemical synthetic drugs) coexist, each with its own strengths and complementing each other. However, in the market economy, they are also competitors. According to statistics over the past 20 years, the proportion of modern medicine (primarily chemical synthetic drugs and their formulations) in pharmaceutical consumption has decreased from 66.7% to around 60%, with a further downward trend; while traditional Chinese medicine (TCM) has increased from 33.3% to over 40%. This suggests the need for the integration of TCM and Western medicine and the development of a new path for China's pharmaceutical industry. The fundamental task of China's chemical pharmaceutical industry development strategy in the 1990s was to strengthen talent and technical preparation to achieve the modernization of China's pharmaceutical industry, laying a solid foundation for further development and modernization through talent cultivation and technological transformation. During this period, the focus should be on improving product quality, developing new products, enhancing economic efficiency, and strengthening pharmaceutical research, education, and overall economic quality.
References
[1] Wang Mingxuan: China Pharmaceutical News, September 30, 1993 edition.
[2] Scrip, 2094, 1996, p. 18. Ibid, 2096, 1996, p. 17.
[3] Wu Dezheng: Foreign Medical Sciences (Pharmacology Edition), 3, 156, 1986.
[4] The Ministry of Health of the People's Republic of China formulated and issued the "New Drug Approval Measures" (effective from July 1, 1985) and supplementary regulations on new drug approval management (released on January 20, 1988), People's Republic of China Ministry of Health. Guanyi, China Pharmaceutical News, January 30, 1992, second edition.
[5] Scrip, 1609, 1991, p. 19. Li Yixin: China Pharmaceutical Industry Journal, 28(2), 1997, 96.
[6] Scirip, 1116, 1989, p. 25. Foreign Pharmaceutical News, 9, 13, 1989.
[7] China Pharmaceutical News, January 17, 1991 edition, Bu Qicheng: China Pharmaceutical News, March 11, 1993 edition.
[8] Yu Zhengwei: Advances in Pharmaceutical Sciences, 13(4), 1989, p. 50.
[9] Chen Biyun: China Pharmacy, 2(2), 1991, p. 1. Ibid, 2(3), 1991, p. 5. (Shenyang Pharmaceutical University, Ji Zhizhong)
Chapter 2: Design and Selection of Pharmaceutical Process Routes
Section Overview
Chemically synthesized drugs are generally prepared from relatively simple chemical raw materials through a series of chemical synthesis and physical processing steps (referred to as full synthesis); or from known natural products with certain basic structures through chemical structural modification and physical processing steps (referred to as semi-synthesis). In most cases, a chemically synthesized drug can have multiple synthetic pathways. The synthetic pathway with industrial production value is referred to as the process route for that drug. In the chemical pharmaceutical industry, the first step is the design and selection of process routes to determine an economical and effective production process route.
In pharmaceutical chemistry and pharmaceutical synthesis reaction courses, new drug research and chemical synthesis methods have been discussed. In new drug development, the first step is through screening to discover lead compounds, synthesizing a series of target compounds, and selecting the optimal effective compounds. The second step involves in-depth pharmacological studies (such as pharmacodynamics, toxicology, and pharmacokinetics), chemical stability research, and pharmaceutical formulation and bioavailability studies on effective compounds deemed promising for development. In the later stage, a certain number of effective compounds need to be synthesized for experimental research, usually in smaller quantities. Even when entering clinical trials (known as Investigational New Drug, IND), the required amount is still not large. This stage generally focuses on product quality, stability, and pharmacological effects. Chemical synthesis is typically conducted on a laboratory scale, with speed often prioritized over economic considerations.
After IND demonstrates excellent efficacy and properties in clinical trials, intensive production research must be carried out, and production scale must be determined based on potential societal demand. At this stage, industrialization, optimization, and cost reduction of the drug process route must be given top priority. The drug process route is the foundation and basis of drug production technology. Its technical advancement and economic rationality are the criteria for measuring the level of production technology. This is particularly important for drugs with complex molecular structures and multiple chemical synthesis steps. It is essential to explore the theory and strategy of process routes, find the optimal pathways for chemically synthesized drugs suitable for industrial production, and also seriously consider economic factors.
Synthesizing a drug can vary in synthetic pathways, process operations, "three wastes" treatment, and the final product's quality, yield, and cost, sometimes with significant differences. An ideal drug process route should be:
① Chemically simple synthesis, meaning the route from raw materials to the drug should be short;
② Use of fewer and more readily available raw materials with sufficient supply;
③ Intermediate separation should be easy in a relatively pure form, meeting quality standards, preferably through continuous multi-step reactions;
④ Preparation should be possible under easily controllable conditions, such as being safe and non-toxic;
⑤ Equipment requirements should not be stringent;
⑥ Minimal "three wastes" with easy treatment;
⑦ Operations should be simple, with separation and purification easily achieving pharmaceutical standards;
⑧ Highest yield, lowest cost, and best economic efficiency.