Summary:
In the production process of solid preparations, one-step granulation and fluidized bed drying equipment are often used equipment. Fluidized bed drying equipment has also evolved from horizontal vibrating fluidized bed dryers to multi-purpose one-step granulators . With the application of emerging technologies such as material processing and intelligent control, fluidized bed drying equipment is also facing new opportunities and challenges in the field of traditional domestic equipment.
As a pharmaceutical enterprise user, when renovating a new project or workshop, the first consideration is to determine the equipment selection and configuration requirements according to the production process and capacity requirements, and to make requirements and explanations on the important components, options, and necessary configurations of the equipment. This is beneficial for users to get a large price-performance equipment with a small investment in Zui. The URS (customer demand) of fluidized bed drying equipment has become the technical document used by the supplier. The equipment supplier needs to meet the configuration information and conditions presented in the document, and the URS also puts forward technical improvement requirements for the equipment manufacturer.
Specific analysis:
At present, domestic GMP has very relaxed DQ requirements for equipment, and equipment requirements are part of DQ. The pre-confirmation we know is only a rough description of equipment selection, material and capacity. There is no detailed configuration requirement for equipment. A major cause of the delay in the manufacture of domestically produced equipment, including fluidized bed drying equipment, control systems, and processing accuracy. As a user of fluidized bed drying equipment, when comparing domestically produced equipment with imported equipment, we are also delighted to find that some domestic equipment manufacturers have begun to try to gradually accept the FDA, EU, and WHO from the detailed equipment customer demand. The required URS mode, tailored equipment according to different products, is also the only way for the development of Chinese pharmaceutical machines.
The wet granulation production process uses a high-speed rotary wet granulator and a fluidized bed drying device to form a granulation linkage line , which has been widely used in many domestic pharmaceutical companies. According to the principle of domestic equipment selection: energy saving and environmental protection . We must put a series of requirements on the equipment when selecting equipment, including technical feasibility discussions with suppliers. Here, we discuss several topics with reference to the UTC terms of the fluidized bed required by the US FDA.
1. Energy saving of fluidized bed drying equipment
The basic principle of fluidized bed drying is to blow the wet particles to a boiling convection state by heated air, and the hot air takes away the evaporated water or the organic solvent to achieve drying of the wet particles, which involves air treatment problems.
At present, many domestic manufacturers have configured the air treatment unit as: primary filter - electric heating (or steam heating) - fan - medium efficiency filter - fluidized bed dryer, it is as simple as this. Obviously, this has a great relationship with the user's needs. The user's request is low, and the manufacturer's configuration is also low. Here we only use the fluidized bed in the GEA granulation linkage line as an example to talk about the configuration and The relationship of energy saving. Air handling unit configuration and parameter requirements:
(1) The inlet air temperature and humidity can be adjusted to the parameter range required by the process, t is 80 ° C, RH is 20%;
(2) The chilled water is cooled and dehumidified, the coil is made of copper tube and aluminum rib type, and the chilled water is chilled water of the process chilled water system, the temperature is 7-12 ° C;
(3) The heat source of the heater is industrial steam, and the requirements for pressure and temperature consumption should be indicated;
(4) The filter adopts (G4+F8+H13) three-stage filtration, and H13 needs to perform PAO leak detection test and verification, indicating the time of detection and replacement;
(5) Box requirements: the inner wall is made of stainless steel in the middle and high efficiency, and the galvanized steel plate is used in the middle and high efficiency. The wall plate has the function of heat preservation and cooling;
(6) The entry and exit of cold water and steam is automatically controlled according to the set temperature and humidity by PLC electric valve or pneumatic valve;
(7) G4, F8, H13 have differential pressure display device, and have differential pressure alarm function in PLC (pressure difference is not displayed on PLC);
(8) The filter is easy to replace and disassemble;
(9) Configure the surface cooler drain trap, the material of the water tray is 304 stainless steel, no water leakage, smooth drainage, no water in the water collecting tray;
(10) The air outlet is equipped with an electric regulating valve, and the opening degree can be controlled by PLC.
This is our requirement for the air handling unit (AHU) configuration.
It is believed that many domestic manufacturers can fully meet these requirements. If domestically produced equipment is manufactured according to this requirement, the quality risk of pharmaceutical production must be reduced, and the detailed verification documents will further improve the technical content of the equipment.
While meeting the GMP requirements, we should also fully consider energy conservation. The energy consumption here involves the defrosting preheating function section, cold water dehumidification, heating section, and negative pressure maintenance in the fluidized bed. According to the URS, if the defrosting preheating section is not required, the setting of the functional section can be canceled, otherwise the investment is increased, the air inlet resistance is increased, and the energy consumption is increased. The cold water dehumidification section and the steam heater are automatically controlled by PLC solenoid valve, and the wind temperature and humidity are set. The conventional fluidized bed drying parameter d is 11g/m3, t is 80°C, and the air inlet volume and exhaust air volume of the fluidized bed are The relationship can be set by the PLC to the negative pressure inside the cylinder and automatically adjust the inlet and exhaust valves. According to the requirements of the FDA, the three-stage filter of the air conditioning unit is very important. The main reason for the large risk of the domestic equipment lies in the filter problem. The selection of the filter is very important. The specification and type of the filter must be clearly stated. G4, F8, H13 must comply with international common standards, can not be cheap and casually made of non-woven cotton, otherwise there will be a large quality risk, of course, the standard filter will increase the resistance of air flow, but our premise is the first Meet the quality requirements.
When the fluidized bed is running, the internal particle movement trajectory is also closely related to the air heat exchange. At present, the bottom air is usually blown up to make the particles convective. The time the particles stay in the air is the time when the water in the particles evaporates. GEA's fluidized bed drying equipment uses a fish scale-shaped air outlet to make the particles spiral upward in the cylinder, effectively increasing the length of the streamline and the time of heat exchange with the air, making full use of energy.
2. Development trend of fluidized bed drying equipment
The fluidized bed drying equipment can be divided into a cylinder part, an AHU part, and an electric control part from the specific structural composition. At present, most domestic manufacturers can basically carry out all production assembly, from a technical point of view, it is wide and not refined, stainless steel processing can also be produced, air handling units can also be assembled, and electrical control of two electricians can solve the problem. The work efficiency is high, the assembly speed is fast, the cost is low, and most of them are copied to other people's equipment. The shape is similar to that of God. This is the current situation of many domestic manufacturers, lacking investment in new product research and development.
Many foreign advanced equipment suppliers are worth learning. They divide the equipment into several parts and carry out division of labor. The fluidized bed drying equipment is made of stainless steel and is simply processed and assembled. AHU is supplied by professional air conditioner manufacturers. It is done by professional personnel, and we do technical coordination work with each other to achieve professionalism and precision. The technical grade of equipment will be improved. This requires us to have a good spirit of cooperation and a serious work attitude, while improving product quality. The added value of the device will also be significantly improved.
As a pharmaceutical company user, we will make detailed requirements for each specific component of the fluidized bed according to GMP requirements, to ensure that the product quality risk is reduced to low, and GMP pursues the process repeatability and traceability of the process, which is even more We require that each step of the production equipment adjustment and parameter setting be clarified and clarified, and the manufacturing of each part of the fluidized bed drying equipment should be standardized, and the design plan, DQ and DS should be strictly implemented. It is very important for suppliers to manufacture a set of advanced fluidized bed drying equipment. Long-term technical discussions with customers are very important. The higher the demand from customers, the more advanced the equipment will be produced. At present, many domestic pharmaceutical companies have gradually moved closer to the FDA. When purchasing equipment, equipment suppliers are required to provide a series of documents, which is precisely the weakness of domestic suppliers. Taking fluidized bed drying equipment as an example, it is necessary to provide:
(1) Mechanical design part: process design, installation design, symbol list, composition list, spare parts list.
(2) Electrical design: software, power distribution chart, SDS, function chart, function description, power distribution cabinet list.
(3) Equipment files: operation manual, maintenance and inspection list, inspection record sheet, touch screen operation instructions, customer training.
(4) Technical data files and spare parts information.
(5) Quality control documents: calibration certificate, sample retention, passivation cleaning, welding gas certificate.
(6) Manufacturing: training, guidance and instructions for welders, training for filming and passivation cleaning.
(7) Quality management: welding quality record, sample retention, weld number chart, welding track output, CD disc.
(8) Verification documents: quality and project plan, FAT plan, unit test check, SAT file.
In view of the above software requirements, the understanding of each manufacturer may be inconsistent, but from the user's point of view, the ability to provide these comprehensive information is exactly what our pharmaceutical company GMP needs.
3. Process repeatability and traceability of fluidized bed drying equipment
In actual production, the operator has to re-set and modify the process parameters of each production equipment. It is not guaranteed that the same product will be produced using the same equipment process parameters, which is not traceable. According to GMP requirements, equipment requirements can store a certain amount of production process parameters to ensure repeatability and traceability. Each user is set according to the number of varieties. Fluidized bed drying equipment generally requires 50 kinds of production processes to be stored, and most domestically produced equipment cannot do this. For a simple example, the spray system is replaced with a nozzle of the same specification. Under the same pressure, the same adhesive is used to spray the same effect. The granulation time and drying time should be reset. This is because when the nozzle is finished, different people and the nozzle produced by the machine tool are different, which requires us to strictly implement the quality standards (including precision) of the nozzle, as one of the necessary conditions to ensure process reproducibility. The processing accuracy should be controlled within a range of a few microns. This requires us to have the rigor and rigor of equipment manufacturing, strict parts inspection and acceptance according to the processing drawings, and sufficient data and documentation support.
The repeatability and traceability of the fluidized bed drying equipment have certain requirements for PLC control systems and mechanical actuators. Examples are as follows:
(1) Designed to be installed inside a locked stainless steel box.
(2) Control the granulation and drying process with Siemens brand PLC (S7-300).
(3) It has the functions of automatic and manual granulation, drying and discharging.
(4) Ability to control and operate the following:
- Intake air, exhaust air volume, control the pressure inside the cylinder;
- Control the inlet air temperature and humidity;
- Control the inlet and steam valves;
- Control discharge
- Control the operation of the peristaltic pump during granulation;
- Control the amount of feed;
- Control online cleaning.
(5) Configure the temperature probe in the inlet air, fluidization chamber, and exhaust air, and display it in the PLC.
(6) Has enough memory to store 50 production processes.
(7) Provide an alarm system.
(8) has the following linkage controls:
- Filter bag breakage stop linkage;
- Granulating slurry low temperature peristaltic pump stop linkage;
- The feed valve is linked with the fan during drying;
- The quick closing valve is linked with the fan;
- Compressed air low pressure alarm linkage;
- Low water pressure alarm linkage during online cleaning;
- AHU cooler, heater outlet temperature, humidity alarm.
(9) PLC can be updated continuously.
(10) PLC has on-site printing parameters, data storage, data access, and data PC connection.
(11) PLC reserves 20% of memory, which is convenient for program upgrade.
This is only part of the enumeration requirements. Different users have different configuration requirements, but to achieve repeatability of process parameters, the basic requirements for PLC are consistent.
4. Online cleaning (WIP) of fluidized bed drying equipment
In the actual use of fluidized bed drying equipment, many people will confuse the concept of CIP with WIP in fluidized bed drying equipment. WIP is the automatic cleaning of the non-removable part after the detachable part of the fluidized bed drying equipment is disassembled, and the CIP is all parts without disassembly, and the fully automatic in-situ cleaning in the full sense, both of which need to be cleaned and verified. Below we analyze the configuration of CIP and WIP.
The CIP of the fluidized bed drying equipment needs to be separately equipped with a set of process hot water system, which is specially used for high-speed rotary wet granulator and fluidized bed drying equipment. The control of hot water system is incorporated into the fluidized bed PLC system, all parameters, The equipment is required to be controlled by the PLC. The parameters or actions of the control include water inlet solenoid valve, liquid level control, steam inlet solenoid valve, heating temperature, circulation pump, water pressure and other items. The process parameters are stored during cleaning verification. It can be reused directly in actual production. In the fluidized bed drying equipment, CIP can be equipped with a rotary sprinkler at the inlet of the air inlet, in the middle of the cylinder, in the upper part of the filter, and at the outlet of the exhaust pipe according to actual needs, and there is initial wash water on the fluidized bed take-up panel. There are several interfaces for hot water and purified water, which can be cleaned online according to the set program, and has the function of insufficient water pressure alarm. In actual use, fluidized bed drying equipment can not achieve CIP in the full sense, because CIP has certain risks, such as the filter bag can not be effectively cleaned, the filter bag is dry, the air inlet screen is not easy to clean, etc. Conduct a rigorous and comprehensive cleaning verification.
In fact, many users use WIP cleaning. Usually used as an oral solid preparation workshop, a coating machine , a granulation line, a washing station, etc., which share a set of process hot water system, which is an independent water circulation system, which connects hot water to the panel and through the fluidized bed drying equipment. The PLC controls the hot water solenoid valve or pneumatic valve to set the cleaning time. The premise of WIP is to remove the filter bag and other detachable parts, and use the initial wash water, purified water, detergent, etc. as needed.
             
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