Conical filtration, washing and drying machine for solvent crystalline active pharmaceutical ingredients

In the production process of solvent-based crystalline active pharmaceutical ingredients, the solid-liquid separation, purification and drying processes can be carried out through centrifugal separation and purification, single-cone or oven drying. Some drugs can also be completed through a single filtration, washing and drying equipment. Traditional filtration, washing and drying equipment can perform multiple functions in the production process through a single device, partially addressing issues such as safety, environmental protection and automation. It has certain advanced performance and is widely applied in the chemical and pharmaceutical industries. However, due to the technical limitations of the equipment, there are risks such as a large amount of material residue, liquid leakage, low drying efficiency and manual intervention in actual production applications. These risks have also troubled many pharmaceutical professionals. Sometimes, based on their actual usage experience, they will add drying equipment after the filtration drying equipment to solve the problem of low drying efficiency. During the discharging process, manual intervention in discharging is adopted to address issues such as residual materials. However, these measures will only increase operating costs and reduce the quality of drug production, treating the symptoms but not the root cause. At the same time, they will also bring unpredictable production risks.

Nowadays, there are various types of multi-functional filtration, washing and drying machines used for the refining and purification of solvent crystalline raw materials in the pharmaceutical industry, but they all have the following defects:

(1) It cannot be stirred quickly and evenly. The typical form of stirring and turning over the material is flat pushing and driving. The contact surface of the material with the jacket is limited, and the bottom filter layer is retained to a certain extent and does not participate in the turning. If the material is slightly sticky, the effect will be greatly reduced.

(2) The washing effect is poor. Conventional stirrers cannot crush and loosen the crystal filter cake, causing it to mix with the cleaning solution in a paste-like or sludge-like state. The crystals are stirred and cleaned through stirring.

(3) The filtration is not thorough, the filter cake material layer is thick, and the filtration area is small. When producing high-demand and high-efficiency products, the filtration needs to be used multiple times, which wastes time and resources.

(4) The drying rate is slow and the heat transfer effect is relatively low.

(5) It is impossible to achieve the closed and automatic turnover of materials.

The main limitations of traditional flat-bottomed filtration equipment such as tank-type three-in-one and vertical dryers are that during the final unloading of materials, the operation is complex and it is difficult to completely discharge the materials. Each unloading process not only takes a long time but also causes a large amount of material residue, affecting the yield and easily leading to the leakage of organic solvents.

Performance characteristics of the conical filtration, washing and drying machine for solvent crystalline raw materials

In order to overcome the problems and deficiencies existing in the production of current equipment for the refinement and purification of active pharmaceutical ingredients, Wuxi Srui has carried out a large amount of design and research and development work, and finally successfully developed a new type of conical filtration, washing and drying machine for solvent crystalline active pharmaceutical ingredients (Patent No. (ZL 202220572661.1) has achieved significant improvements in the technical performance of pharmaceutical equipment. By enhancing the equipment structure and optimizing the process flow, the system processing effect has been improved. It occupies less space, has a lower cost, is convenient for production and processing, reduces labor intensity, and greatly decreases material loss. Moreover, for operations with particularly high sealing requirements such as toxic or flammable and explosive substances, it is especially suitable for operations that have almost no impact on workers' health or the surrounding environment, while enhancing the performance characteristics of the three-in-one filtration, washing and drying

(1) The filtration area has been significantly increased: The conical filtration area is set. For equipment of the same diameter, the conical filtration area is 2 to 2.5 times that of the flat bottom.

(2) Automatic and complete discharge: The discharge port is located at the lowest position of the equipment, automatically and completely discharging. Combined with the forward and reverse rotation of the internal stirring, generally loose materials can be discharged without residue.

(3) Excellent drying effect: The three-in-one dryer is equipped with an internal heating conical spiral stirring. Its multi-deformation design enables materials with different properties to achieve an ideal three-dimensional flipping effect. The jacket heat exchange in the main body of the equipment is fully utilized, and each part of the material is fully heat-exchanged.

The conical filtration, washing and drying machine for solvent crystalline active pharmaceutical ingredients integrates solid-liquid separation, washing and filtration, and low-temperature vacuum drying of crystals. It completes the above process operations in a sealed container, effectively preventing human contamination and ensuring the intrinsic quality of the drug. Its process flow is: Raw material medicine crystallization tank crystallization → Three-in-one multi-functional filter (filtration - washing - drying)→ automatic discharge. This new operation features a simple process, sealed operation, convenient material conversion, high production efficiency and good product quality. The entire production process, from the feeding of the crystalline solid-liquid suspension to the automatic discharge of the raw materials after drying, is completed in one container, reducing the total number of raw material drug production equipment. This not only lowers the investment cost but also shrinks the area of the factory building.

Technical improvement of conical filtration, washing and drying machine for solvent crystalline active Pharmaceutical ingredients

(1) Equipment main body

The main body of the equipment consists of an upper cylinder with a head, a lower cone with a bottom plate and a conical filter. The lower cone and the conical filter adopt a split structure. The lower cone is automatically raised and lowered through a lead screw reducer installed on the upper cylinder bracket.

② The lower cone can be raised and lowered, enabling rapid and thorough cleaning, maintenance and replacement of the detachable conical filter.

③ The internal structure of the equipment features smooth transitions without dead corners.

④ The container is equipped with cleaning balls, which can automatically complete the cleaning inside the container.

⑤ The system is equipped with a dust collector that can be heated, insulated, vacuumed and used for reverse blowing.

⑥ The jacket of the tank body is equipped with heating half tubes to ensure heat exchange efficiency.

⑦ The process connection pipes adopt ISO2852 clean quick-opening or flange connection (the clamps are high-pressure clamps; the feed port, blasting vent port, pressure transmitter port, mother liquor outlet, and jacket inlet and outlet are flange connections), meeting the requirements of pressure vessels.

(2) Insulation of the main body of the equipment

The outer surfaces of the upper cylinder with a head and the lower cone with a bottom plate are provided with insulation layers for heat insulation and to reduce heat loss.

② Insulation material: aluminum silicate;

③ The filling thickness of the insulation material should be no less than 50mm(the shell layer should not exceed 40℃).

(3) Detachable conical filter

The filter screen is composed of six layers of metal sintered mesh: one top protective layer, two actual filtration layers, one filtrate distribution layer, and two support and reinforcement layers.

② The conical filter adopts a segmented design, featuring high structural strength and minimal deformation during pressure filtration, thereby enhancing the filtration effect.

③ It can achieve multi-stage independent filtration, segmented reverse blowing and washing, etc. The solid-liquid separation is thorough and there will be no problem of filtration short circuit.

④ The filter screen assembly adopts multiple layers of high-strength sintered filter screens welded and fixed on metal supports, and then is firmly fastened to the container base as a whole. The material contact surface is a smooth top protective layer of 6 layers of metal sintered screens to prevent material residue problems.

⑤ The filtrate collection base is equipped with a balance pipe interface, which is connected to the vacuum port of the dust collector through the balance pipe, effectively preventing damage to the filter screen caused by the vacuum state during the drying process

⑥ The conical filter can be disassembled conveniently. The filter medium and the perforated plate are integrated, and the outside of the perforated plate is the filtrate chamber.

The distance between the filter holes on the four edges of the filter and the inner edge of the cylinder should be as short as possible (preferably ≤5mm) to reduce the filter blind spots

⑧ A special sealing structure is adopted between the conical filter and the inner wall of the lower cone. The upper and lower sealing gaskets of the filter's sintered plate are made of O-shaped ethylene propylene diene monomer (EPDM) coated with FEP. The sealing structure reduces chemical residue, facilitates cleaning, and ensures reliable sealing without any leakage.

(4) Stirring shaft

① The sealing between the stirring shaft and the container adopts a set of sterile dedicated dry double-end face mechanical seals, equipped with wear collection cups to reduce contamination of the materials.

② The stirring paddle is equipped with a variable frequency speed regulation explosion-proof drive variable frequency motor. Explosion-proof grade: ExdIIBT4, protection grade: IP55.

③ The stirring shaft adopts an internal heating helical ribbon structure, with a natural and smooth transition, ensuring the minimum degree of damage to the product's crystal form, while increasing the heating area and enhancing the drying speed.

④ Double internal heating helical ribbon agitator, during operation, the force is evenly distributed, the deformation caused by the rotation of the main shaft is small, and the heat transfer area is large.

⑤ Variable pitch helical ribbon agitator: It improves the three-directional compound movement of the material in the axial, radial and circumferential directions inside the machine, making the stirring and mixing effect reach the best state.

⑥ An adjustable scraper is set at the lower end of the shaft, closely adhering to the bottom plate of the cone to improve the stirring and mixing effect of the material at the bottom of the cone.

(5) Discharge valve

① The installation structure of the new type of discharge ball valve ensures that the sealing ball closely adheres to the plane of the base plate, achieving discharge without dead corners.

② The valve cover and valve body adopt an easy-to-open structure, which is convenient for opening and cleaning.

③ The valve cover and valve body can be automatically opened and discharged, and the discharge time can be set.

④ The discharge valve can be cleaned online, meeting GMP requirements.

⑤ The flange between the valve head and the tank body adopts a formed O-shaped PTFE ring soft seal, which ensures a reduction in drug residue, facilitates cleaning, and guarantees reliable sealing.

(6) Sampling valve

A set of plunger type sampling valves is installed on the bottom plate of the lower cone for online sampling, which complies with GMP requirements.

② The sealing part at the rear end of the sampling valve body that comes into contact with the material adopts an O-ring coated with FEP silicone rubber.

③ Set up online cleaning;

(7) Dust collector

① It is installed on the head of the filter through a quick-opening connection;

② The design parameters of the dust collector are consistent with those of the filter, washing and drying tank, such as the same pressure and temperature, the same material, and the same surface finish treatment.

③ The filter element is made of five layers of metal sintered mesh.

④ Filter element material: 316L, filtration accuracy: 10 microns;

⑤ The dust collector is equipped with heating, vacuum and high-pressure nitrogen connection pipes, which can integrate functions such as heating, heat preservation, reverse blowing and vacuuming into one.

(8) Cleaning device

Three 360° cleaning spray balls are set on the top of the tank for cleaning inside the tank. They adopt a removable sleeve structure, which meets GMP requirements.

② The top of the head of the filter washing dryer is equipped with a cleaning rod with a casing structure for cleaning the lower part of the mechanical seal and the main shaft.

③ The cleaning balls should be selected from Avala Lafa or an equivalent brand, and 360° cleaning without any blind spots is required.

(9) Safety protection

① Filter screen safety protection: The filtrate collection base is equipped with a balance pipe opening, which is connected to the vacuum port of the dust collector to prevent damage to the filter screen caused by the vacuum state during the drying process.

② Safety protection for opening the maintenance manhole: The stirring blades are not allowed to be started when the maintenance manhole is not closed.

③ Safety protection of the discharge valve: The discharge valve head can self-lock after being tightly closed. When the tank is under pressure, the discharge valve head is not allowed to be opened. When the discharge valve cover is not installed properly, the stirring blades are not allowed to be started.

④ Overload protection for the inverter motor;

⑤ Overvoltage/undervoltage protection of the frequency converter;

⑥ Overcurrent protection of frequency converter;

⑦ Phase loss protection of the frequency converter;

⑧ The vent valve and the vacuum valve are interlocked and cannot be opened simultaneously.

⑨ Interlock the vent valve with the regulating valve and vent slowly.

Under emergency stop safety protection, the operating status and control parameters of the equipment can be displayed.

Wuxi Shuangrui is committed to promoting technological innovation in closed-loop circulation dryers and multi-functional filtration, washing and drying machines, and values the full trust given by customers. Intellectual property rights are the common lifeline of Shuangrui Machinery and its customers. At Wuxi Sunray, we adhere to the foundation of our business as honesty and dedication, and maintain a zero-tolerance policy towards infringement. We resolutely crack down on any criminal acts that infringe upon intellectual property rights. This is the supreme responsibility, obligation and commitment of Wuxi Sunray. We must sincerely repay our customers' trust and completely eliminate any infringement.

Conical filtration, washing and drying machine for active pharmaceutical ingredients (a certain pharmaceutical factory in Xuzhou)