Three-Dimensional Layout And Material Transportation Of Oral Solid Preparation Production Plant

Oral solid preparation production plant layout has two-dimensional layout and three-dimensional layout, and there are various material conveying methods. Through case analysis, the application of gravity flow material conveying and automatic three-dimensional warehouse in three-dimensional plant layout is explained, and the three-dimensional layout and material conveying methods are summarized. Advantage.

Part 1 Overview

Oral solid preparations are common dosage forms of medicines, such as oral granules, tablets, and capsules. The materials of oral solid preparations are usually solid materials, such as starting powder raw materials, semi-finished products such as granulated granules, blended granules, compressed plain tablets, coated tablets, etc. In addition, packaging materials such as bags and aluminum foil are also required during production , plastic sealing film, label, carton, etc. These raw materials, semi-finished products, packaging materials, etc. all need to be transported in the production process, that is, material flow.

Material flow is a very important factor that needs to be considered in the layout design of oral solid preparation plants. Most of the traditional oral solid preparation plants have a flat layout. The production process equipment is concentrated in a large flat layer, and the materials are concentrated on the same level for transfer. Usually, the stainless steel intermediate bulk container IBC (Intermediate Bulk Container) is transferred by manual or hydraulic trolley, or by vacuum feeding or discharging. The lifting and lowering of the material height can be realized by lifting the stainless steel bin with a hoist. The above methods require manpower Or electricity as an energy source requires manual participation. In recent years, with the development and improvement of the pharmaceutical equipment manufacturing industry, the application of three-dimensional layouts in which production processes are distributed on multiple floors has become more and more common. The process of conveying materials by gravity flow has become more and more common. .

Part 2 Case Study

The article takes the construction of a project of a famous German pharmaceutical group in Jiangsu Nantong Economic and Technological Development Zone with an annual output of 2.4 billion oral solid preparations as an example, and discusses the three-dimensional plant layout and the application of gravity flow in oral solid preparation production plant facilities. The technical person in charge of the basic design summed up his experience in the three-dimensional layout design of the factory building.

2.1 Three-Dimensional Layout Of Plant Facilities

The project sets up a separate production building and a separate storage and logistics building, and a corridor is set up between the two buildings to facilitate the transfer of raw materials, finished products, packaging materials and semi-finished products. The production building has a total of four floors. The first floor mainly includes packaging workshops (inner packaging and outer packaging) and other public engineering auxiliary equipment; the second floor mainly includes tablet pressing workshops, coating workshops, fluidized bed unloading-granulation , and the clean changing room in the production building; the third floor mainly includes the fluidized bed granulation workshop, the tablet feeding room, the transfer bin (IBC) cleaning room and the QC quality laboratory; the fourth floor mainly includes the fluidized bed feeding room and other public works auxiliary equipment. In addition, there is a hollow three-dimensional automatic temporary storage area in the middle of the production building, equipped with three-dimensional shelves and conveyor systems, to store and transfer raw materials, finished products, packaging materials, semi-finished products, etc. to and from the floors and warehouses of the production workshop. The three-dimensional layout of the production building is conducive to the materials being sent to the highest floor, which is the fourth floor, through the conveyor system in the automatic temporary storage area. Following the production process, the materials are transported to the lower floor sequentially by using their own gravity as much as possible. Generally, the material is first fed into the wet mixer or fluidized bed granulation equipment on the third floor from the feeding room of the fourth fluidized bed, and then enters the wet mixer or fluidized bed cavity through the pipeline, and then fluidized after the granulation and drying are completed. After the bed is discharged from the lower flap, it is transferred to the lower layer (the second layer) to complete the dry sizing and mixing process. The mixed granular material is transferred back to the fully automatic temporary storage area in the turnover silo, and then passes through the conveyor system again. It is sent to the tablet feeding room on the third layer, and after docking with the unloading station, it is transported by gravity from the unloading pipe to the tablet press machine on the lower (second) floor. After passing the in-production quality inspection (IPC), the semi-finished products return to the fully automatic temporary storage area and are transferred to the feeding hopper of the packaging line on the first floor of the lowest floor for packaging. The warehousing and logistics building has two floors. Except for the hollow shelf area of the warehouse, the first floor mainly includes the weighing and batching workshop, and the second floor mainly includes the weighing and batching unloading room. The materials are sent to the second floor through the warehouse conveyor system. After pretreatment such as crushing and sieving is completed and the ingredients are weighed, the materials are transported to the lower floor in turn by their own gravity and enter the IBC transfer silo, and enter through the corridor between the two buildings. The three-dimensional automatic temporary storage area of the production building, and the corridor is set as a D-level clean-up area of the pharmaceutical plant [1].

2.2 Application Of Gravity Conveying In The Production Process Of This Project

(1) Ingredients weighing process. As shown in Figure 1, the batching and weighing station is set up on the second floor of the warehouse and logistics building. The material pallets in the warehouse can directly reach the weighing and batching area on the second floor through the conveyor system. The measuring hopper relies on gravity, and is put into the stainless steel transfer bin IBC on the first floor below through the feeding pipe. The transfer silo enters the corridor through the elevator and transfers to the intermediate warehouse or the next process equipment (mixing or fluidized bed granulation). There are three oral solid preparations for the project, and each product has a different formulation of process materials. Some raw materials need to be pretreated by crushing and sieving. Therefore, a pulverizer and a sieving machine are installed before feeding, and the materials are taken according to the formula after pretreatment. Weigh and put into the weighing hopper through the pallet elevator. The weighing hopper is equipped with a weighing device to realize automatic weighing. The stainless steel receiving container on the first floor is automatically docked with the elevator and the feeding pipe. After blanking, a floor scale is installed on the first floor to check the weight.

The traditional fluidized bed usually uses a mobile silo to discharge the material, and then transfers the material to the dry granulator for granulation and then enters the turnover silo through vacuum transmission. In this way, when the mobile silo is removed from the fluidized bed, the fluid The remaining materials at the joint between the cylinder body and the mobile silo will be exposed and produce dust, resulting in material loss. In addition, during the transfer of the mobile silo, material transportation, and granulation operations, the material is exposed, which will increase the risk of pollution and is not conducive to the product. Improved quality, slightly less Good Manufacturing Practice (GMP) compliance. In contrast, the gravity conveying process has the advantages of airtightness, continuity, energy saving, high efficiency, low dust production, and less pollution.

(2) Tablet feeding process. As shown in Figure 3, the IBC silo of the project is transferred to the upper layer (the third layer) of the tablet press. After the IBC silo is connected to the feeding station, the material is directly transported from the upper layer to the lower layer of the tablet press through the pipeline. In the layout of large flat-floor workshops, vacuum conveying can be used to transport materials from the silo to the top of the tablet press, and a hopper elevator can also be used to lift the IBC silo to the top of the tablet press. After the silo is turned over, the other After the discharge port is docked with the feed port of the tablet press, the material is unloaded and produced. Obviously, compared with hopper lifting and flipping feeding or vacuum conveying feeding, the tablet pressing process adopts gravity unloading, which is safe (avoiding the risk of personnel being mechanically injured when the hoist lifts the IBC silo or when it is turned over), airtight and energy-saving , high efficiency, and space saving in the clean room (there is no need to install turnover bins and hoists in the tablet pressing room).

2.3 Fully Automatic Temporary Storage Area And Material Conveying

The production process of oral solid preparations usually requires intermediate process quality control, quality inspection of raw materials and semi-finished products, such as the appearance of semi-finished products, moisture after granulation and drying, tablet weight, tablet thickness, and hardness after tableting and coating , friability, disintegration, etc., can only be released to the next production process after passing the test, which requires a certain temporary storage area in the factory building. At the same time, due to the three-dimensional layout of the project, the production process rooms are distributed on different floors, and the production materials ( Raw materials, intermediates, packaging materials, etc.) and containers (IBC, bags) need to be transported across floors, so a hollow three-dimensional fully automatic temporary storage area is centrally set up in the middle of the production building, and the conveyor system configured in the temporary storage area is located in the middle of the production building , each floor is equipped with a receiving and transferring room docked with the conveyor system. Materials and containers can be transferred between floors and intermediate warehouse shelves by a fully automatic temporary storage area conveyor system. The fully automatic temporary storage area where the high-level shelves and stackers, material pallet automatic transportation equipment, and conveyor system are located is set as a pharmaceutical clean area, which is at the same level as the production process clean area, which avoids the need for materials or hoppers that are usually transported to pass in and out. The risk of cross-contamination in clean and unclean areas. Different from the scattered temporary storage areas usually used in the layout of large flat-floor workshops, the centralized setting of fully automatic temporary storage areas can reduce floor space, make full use of space, reduce manual operations, improve logistics efficiency, and improve the automation level of production management (using computer-controlled Accurate and error-free information management of goods information, automatic identification of goods, reducing possible errors in storing goods, fast and convenient, and improving work efficiency), and also reducing possible injuries to people when handling goods, safety higher.

2.4 Material Transportation And Dust Treatment Of Three-Dimensional Layout Workshop

Material transportation is one of the important links of dust exposure. The current version of GMP has higher requirements for dust treatment. The production process of the project has many dust-producing steps, and the products contain hormones, which are helpful for eliminating cross-contamination, protecting the health of operators, and reducing environmental pollution. There are higher requirements in terms of pollution. The three-dimensional layout adopts gravity flow to convey materials, which has higher airtightness and is more in line with GMP requirements in terms of dust treatment. It reduces labor, improves labor efficiency, and protects the health of employees. The cost of cleaning and sewage treatment takes into account energy saving needs.

2.5 Matters Needing Attention In The Three-Dimensional Layout Plant Gravity Flow Material Transportation

① Three-dimensional workshop layout The production process is distributed on multiple floors, requiring cross-layer operations. For example, the transfer of materials to the lower floor can only be carried out after the turnover bin and the feeding station are successfully connected. The upper and lower floors need to communicate efficiently to avoid operational errors. Speakers, cameras and other equipment are used to ensure the unified operation of the upper and lower layers, and to standardize the SOP procedures for operations. At the same time, RFID (Radio Frequency Identification, radio frequency identification technology) electronic tags are used to identify and track materials to avoid docking errors; ②Gravity flow transfer materials may have poor material flow in the transfer pipeline, the solution can be adopted by inner bags and The double-layer feeding tube composed of outer stainless steel tubes, compressed air is passed between the two tubes to control the expansion of the inner bag, which is equivalent to setting an adjustable damping mechanism to realize slow feeding, thereby improving the situation of poor material flow. The inner bag is a disposable soft bag, which is discarded after use to reduce dust and equipment cleaning; ③The material transportation of the three-dimensional plant layout materials should pay attention to the combination with other transportation methods except gravity flow, through value flow analysis, cost estimation and risk The method of evaluation is to select the most economical and applicable material transportation method in the process operation process.

Part 3 Conclusion

The three-dimensional layout factory building based on gravity flow conveying materials reduces the temporary storage and transfer of materials, shortens the turnover time of materials and containers, improves the efficiency and utilization of equipment, and is more in line with the concept of lean production and automated continuous production. From the perspective of compliance with the Good Manufacturing Practice (GMP), improving product quality assurance, safe production, production cost control, protecting personnel health, saving energy and reducing environmental pollution, making full use of space, and improving the space utilization rate of clean areas, three-dimensional The layout of factory buildings has more advantages and development potential.