Analysis On The Process Design Of Benoate Tablet Production Workshop

Benoate, also known as Painolate, Benluolai, and Jierean, its chemical name: 2-acetoxybenzoic acid p-acetylhelylphenyl ester, molecular formula: C17H15NO5, is a good non-steroidal Anti-inflammatory analgesics and cyclooxygenase inhibitors. Benoate tablet is a lipophilic compound synthesized by aspirin and paracetamol, which not only has significant analgesic, anti-inflammatory, and strong antipyretic effects, but also overcomes the disadvantages of aspirin for suddenly lowering blood pressure, and has good lipophilicity. Solubility, gradually dissolves in the blood to become a metabolite completely different from aspirin and paracetamol, so the effect and adaptability are better. Benoate tablet is an esterification product of acetaminophen and aspirin, and its mechanism of action is to produce corresponding effects by inhibiting the synthesis of prostaglandins (PG). Its effects last longer than aspirin or acetaminophen. After oral administration, it can reduce the synthesis of PG by inhibiting central nervous system cyclooxygenase, so as to achieve antipyretic effect; through the inhibition of PG synthase in peripheral tissues, it can produce analgesic effect; in the inflammatory reaction, the synthesis of PG is affected Inhibition can achieve the corresponding effect. Benoate tablets can effectively reduce the pathological hyperactivity state in the temperature center of the human body, thereby lowering the temperature of the human body; make the blood vessels of the skin expand, increase sweating, accelerate heat dissipation, and achieve a good antipyretic effect; it can also inhibit prostaglandins, The production of chemical substances such as histamine, and resist its irritation, stabilize the lysosomal membrane and achieve good anti-inflammatory effect; it can also reduce the permeability of inflammatory tissue, improve microcirculation, and enhance anti-inflammatory effect. Aspirin and paracetamol are chemically prepared, and it is suitable for runny nose, headache, fever and joint pain caused by colds. Because there is no decomposition of the gastrointestinal tract in the body, it can effectively avoid the stimulation of aspirin to the gastrointestinal tract, and at the same time avoid some side effects caused by medication. It is suitable for rheumatism, rheumatoid arthritis, neuralgia, headache, cold and other diseases It has a certain therapeutic effect.

Benoate tablet has the characteristics of quick effect, high dissolution rate, good bioavailability, and low incidence of side effects, and will not be hydrolyzed in the gastrointestinal tract, so it can effectively eliminate the effects of common antipyretic and analgesic effects on the gastrointestinal tract. Stimulating effect, and long-term use without addiction and dependence. It does not affect the central nervous system at normal temperature, and is suitable for the temperature regulation center of the human body and infants who have not yet fully developed, and the effect is more ideal and safer. Benoate tablet has played very good effect in relieving patient’s fever, relieving pain, etc., and has good market and social benefits. Therefore, it is very necessary to study and design a scientific and advanced technological route of beinolate tablets.

Part 1 Production Process Analysis

Benoate was synthesized for the first time in the Netherlands. In 1975, China began to research and develop it, and then promoted it throughout the country. With the advancement of technology, the production technology of Benoate has also been further developed. In the structure of beinolate, there are many ester bonds and amide bonds that can be hydrolyzed, and these two chemical bonds are the key to the synthesis of required drugs. At present, the synthetic route of beinolate is mainly divided into two parts: the first part is to utilize acetylsalicylic acid and thionyl chloride to generate o-acetylsalicyloyl chloride; the second part is to use o-acetylsalicylic acid and N-( 4-hydroxyphenyl)-N-methylacetamide undergoes an esterification reaction to finally generate 4-acetamidophenyl acetoxybenzoate, the main component of beinolate. During the preparation, using DMF and a phase transfer catalyst to replace the traditional pyridine in the first step and acetone in the second step respectively, not only significantly reduces the reaction temperature, but also greatly shortens the reaction time, and the yield of the product is also greatly improved. Improve greatly.

The production process of beinolate tablets is shown in Figure 1. The synthesis part of the raw material (benoate) shows a flow chart with control points, the whole synthesis steps of the raw material can be completed in the same reactor, the first step reaction is opened 201, 202, 203 to combine acetylsalicylic acid with dichloro Sulfoxide and DMF were put into the reactor. After the reaction is over, open 204, 205 and put N-(4-hydroxyphenyl)-N-methylacetamide and other materials into the reactor. After the reaction, the raw material of beinolate is obtained; Powder sieving and milling are a key link in preparation engineering, which can promote drug dissolution, improve drug bioavailability, and improve its fluidity, which is helpful to improve the quality of preparations. During the specific operation, the raw material aspirin and acetaminophen are mixed and pulverized, so that the two can achieve a uniform mixing effect during the pulverization process. After grinding, the mixed materials with various sizes are separated according to different particle sizes by sieving technology. The granules conforming to the standard size are then mixed with binders, starch, dextrin, etc. to produce wet granules. Mixing is to ensure the uniformity and consistency of ingredients, which is helpful for subsequent pharmaceutical production. The wet granules are then dried. The moisture removed during the drying process is mainly water, and air circulation is usually used to take away the water. The wet granules produced during granulation contain moisture or other viscous substances, which will form agglomerates during drying, causing the particle size of the dry powder to be too large, which will affect the fluidity of the powder and further affect the quality. Use a granulator to grind the dry powder into more uniform, flowable granules. In this design, lubricants (sodium carboxymethyl starch and micropowder silica gel) are mixed with the above-mentioned dried medicine granules to make the medicine powder more uniform. After total blending, it is directly compressed using a tablet machine. After coating and packaging, packaging is the last process in the tablet process, which includes inner, middle, outer packaging, instructions, etc. The packaging method used in this design is a single-dose, blister-type, high-quality aluminum foil is used as the substrate, and the name, usage, dosage, etc. of the drug are printed on the back, and the Benolate tablet product is finally obtained.

Part 2 Workshop Layout Analysis

The purpose of workshop layout is to rationally arrange the equipment used in the factory, so as to ensure the future production of the factory, product quality and economic benefits. Special attention should be paid to infrastructure construction, which will directly affect the development of the entire pharmaceutical factory. Article 46 of the Good Manufacturing Practice (New GMP) document states: In order to reduce the risk of contamination and cross-contamination, workshops, production facilities and equipment should be based on the characteristics of the drugs produced, the process flow and the corresponding cleanliness level requirements Reasonable design, layout and use. Reasonable layout will affect the overall management of the preparation of drugs, safety hazards, difficulty of maintenance work, increase the probability of cross-contamination, power consumption and the cost of construction, air conditioning purification and other equipment.

According to the relevant requirements of GMP, the car is divided into various partitions, which are independent of each other, and only doors for people and objects to enter and exit are set. The entrance of the factory building is equipped with men’s and women’s changing areas, sinks, buffer rooms, disinfection systems, etc. All equipment, sanitary ware, and containers entering and leaving the workshop must be disinfected and equipped with sufficient cold and hot water sources. The layout of the whole workshop is relatively reasonable, and it is basically carried out in a rectangular studio surrounded by corridors in the clean area, which can not only facilitate production, but also ensure the hygiene of the workshop. In order to ensure indoor air circulation, the plant is equipped with ventilation facilities and is equipped with sufficient exhaust devices.

The production workshop of this design is a single-story workshop, mainly composed of production area (clean production area and general production area), power area, management area and other departments.

The production area is divided into a clean production area and a general production area. The general production area has hygiene requirements, but no cleanliness requirements; while the clean production area is mainly controlled by particles and microorganisms, and must meet the requirements of a D-level clean area. Standardize the ambient temperature, humidity, pressure difference, illuminance, noise, etc. in the pharmaceutical factory. In addition, air-conditioning purification devices should be installed in the production area to achieve efficient ventilation, and measures such as temperature control, humidity control, air purification, and filtration should be installed to ensure the safety of pharmaceutical production. Secondly, storage areas for raw materials, semi-finished products and finished products that meet the production scale should be equipped, and should be as close as possible to their production areas to reduce cross-contamination during transportation. The pending drug area, the qualified drug area, and the unqualified drug area must all be carried out in the storage area. The weighing and batching area should be adjacent to the original and auxiliary material room, and the indoor air cleanliness should be consistent with the original and auxiliary material room; all areas of the prevention equipment, sanitary ware room, and disinfection room must be cleaned in a dust-free area. Its cleanliness must be consistent with the cleanliness of the ambient air in the area; in order to transfer raw and auxiliary materials, packaging materials and other items, an air door or transfer window (cabinet) must be provided between the cleaning or disinfection room and the clean room. The outlet of the waste generated in production should not share the same air valve or transfer window with the raw material inlet, therefore, special transfer devices are respectively set up. In addition, safety doors should be set up in the clean area so that in the event of an emergency, personnel can be separated to ensure safety.

The power zone is mainly to provide the required electric energy, heat energy and water energy for the factory. In this case, the power area mainly includes two parts: purified water preparation room, power distribution and air conditioning room.

The management area in the pharmaceutical workshop is also essential. In this case, the management area is mainly divided into office area and duty room. The setting of the management area is to establish a set of management system in line with this production workshop to ensure the quality of products and the health of employees, and manage the arrangement of raw materials, auxiliary materials, packaging materials and finished products, cleaning of the workshop and the safety of personnel, etc. .

In addition, in order to prevent cross-contamination between people and logistics, the workshop has set up special routes for people and logistics. The staff has set up a special cleaning room, toilet, lounge and office area, etc., which are composed of a rain gear storage room, a changing room, a laundry room, a washing room for storing coats, and a shoe changing room.

Part 3 Plant Layout

This paper designs a single-story factory building. The factory building structure is a reinforced concrete structure. Although its mass and volume are large, it has the advantages of high strength, good seismic performance, high rigidity, and good fire resistance. It can replace steel structures in many occasions. Thereby saving steel. In-situ pouring is adopted, and the concrete grade is C15. The magnitude of the earthquake at each site of the plant is basically 8. The outdoor lightning protection grounding of buildings shall be carried out in accordance with relevant regulations. In the overall layout of the factory building, a certain distance should be maintained between buildings to form a circular passage to meet the needs of fire prevention, transportation and other operations. The process equipment in the production workshop has set up safe passages in accordance with the requirements of the technical specifications, and reserved a certain interval of work. The design conforms to the national industry hygiene standards and related technical regulations, and takes corresponding measures to ensure the safety, hygiene and health of workers and create a civilized production environment for unsafe factors that endanger production and production and dangerous factors that endanger workers’ health.

There are five doors in the factory building, of which there is a door in the east for employees to go in and out; there are two doors in the west, one for the exit of finished products and the other for the entrance of packaging materials; It is used for the import and export of raw and auxiliary materials; there is a safety door on the buffer road to facilitate emergency evacuation. The windows of the factory building must not only meet the requirements of lighting and ventilation, but also meet some other special requirements. For example, the transfer window can be used to transfer goods, which can effectively prevent drug pollution.

Part 4 “Three Wastes” Treatment

Benoate tablets will produce some environmentally harmful by-products during production. Therefore, they must be treated before they can be discharged. The by-products mainly include waste water, waste residue and exhaust gas.

4.1 Waste Water And Treatment Measures

The main sources of wastewater in this workshop are process wastewater and personnel cleaning wastewater. The solution adopted is to centrally discharge the sewage into the sewage treatment plant and be treated by professionals.

4.2 Waste Residue And Treatment Measures

The waste residue in this workshop mainly comes from workshop waste residue, coal cinder from boiler room, waste from production process, household garbage, etc. Transport the waste residue to the waste storage place designated by the county in time, where the coal residue can be directly buried in the ground, or burned as fuel for crops; the rest of the waste should be disposed of according to the designated waste classification method.

4.3 Exhaust Gas And Treatment Measures

The waste gas in this workshop mainly comes from the waste gas produced by the coating liquid during coating in the workshop. In order to protect the atmospheric environment, the waste gas produced in the workshop can only be discharged into the atmosphere after specific treatment and meets the specified requirements.

Part 5 Summary

The main purpose of this design is to design a reasonable workshop process for the production of Benoate Tablets. In terms of the layout of the production workshop, the design principle is to be as simple, convenient and rational as possible on the basis of meeting the requirements of GMP, so as to provide a good environment for improving production efficiency. In terms of people and logistics direction setting, people and things have their own entrances and exits, which can avoid cross contamination and meet the requirements of GMP standards. At the same time, in terms of storage of raw materials and finished products, the production workshop is directly connected to the warehouse during design, which is very Greatly facilitates transportation. In a word, this article provides a reasonable and efficient plan for the production of beinolate tablets, which complies with the requirements of GMP.