Development trend of raw material medicine crystal filtration centrifuge

The development trend of the raw material medicine crystal filtration centrifuge is to realize the liquid-liquid, liquid-solid, liquid-liquid/solid separation equipment in the centrifugal force field. It has a history of more than 100 years, and the nuclear industry development has succeeded in the production of gas-gas. Separated equipment, equipment that uses the centrifugal force field to achieve phase separation of materials has many branches. The solid phase is filtered from the suspension and is a branch of the liquid-solid centrifugal separator. In the 19th century, various crystal filtration centrifuges appeared. According to the size of the separated particles, the centrifuge discharge method can be divided into: (1) filter cake filtration, filter cake into a fixed layer intermittent discharge centrifuge (hereinafter referred to as filter cake filtration fixed layer centrifuge), such as three-legged artificial Unloading, hanging bag unloading centrifuge, scraper unloading centrifuge, turning bag centrifuge, etc.; (2) filter cake filtration, filter cake into moving layer continuous discharge centrifuge, such as horizontal pulsation unloading, screw unloading Material, unloading, vibration discharge, centrifugal force discharge centrifuge, etc. In the pharmaceutical industry crystal (or amorphous solid phase) filtration, filter cake filtration fixed layer centrifuge is widely used. These models have appeared in the general equipment, and can be used in chemical, light industry, food, pharmaceutical and other production. In the 1990s, centrifugal filters were introduced for the production of pharmaceuticals. They were modified on the basis of general-purpose models and were used in GMP for aseptic processing. For example, the HZ-ph series of Krauss Maffei is shown in Figure 1. The HSZ-ph of Ferrum The series, Heinkel's HF series are shown in Figure 2. Okawara's CRF series and Fima; Comi/Condor and other companies produce different types of pharmaceutical centrifugal filters. 1 Theoretical basis of filter cake filtration under pressure state At present, the separation operation of medicinal centrifugal filter introduced by foreign countries and domestic technology introduction or imitation is carried out by filter cake filtration method. Its design is based on the filter theory of pressure state filter cake. Filter cake filtration rate equation under pressure (the liquid phase flow in the filter cake layer is stagnant <1m/s=:...(1) where: V- escapes liquid phase after filtering θ time; A-filtration area; Θ-filtration time; filter cake resistance of Rc-unit filtration area; filter medium resistance of Rm-unit filtration area; p-filtration pressure; μ-liquid phase viscosity; JAStorrow et al. based on basic equations of pressure filtration in the 1950s Establish a centrifuge filter cake filtration rate equation (see Figure 3): (2) where: ρc-liquid phase density; ω-angular velocity; k-filter cake inherent permeability; h-rotor effective length; HP Grace is included The ratio of filter cake specific resistance, void ratio and other factors on the basis of the above gives the rate equation: (3) where: α-filter cake specific resistance; W- filter cake in the total mass of solid particles; W = πhρs (1 ε)(r32-r22); S-solid phase density; ε-void rate formula (2) (3) is still one of the basic equations of filter cake filtration fixed layer centrifuge filtration theory. 3 foreign filter cake filtration fixed layer centrifuge features abroad introduced filter cake filtration The different types of fixed-layer centrifuges are mainly determined by the unloading method: (1) manual unloading, suspension as above, three-legged, etc. These centrifuges have been widely used in pharmaceutical production, with industry. A considerable part of the development is replaced by the automatic unloading machine type; (2) automatic unloading, recommended for the filtration of the drug crystal filter cake fixed layer centrifuge representative machine type horizontal scraper discharge centrifuge, bag centrifuge and centrifugal filter Gas discharge centrifuge integrated with fluidized bed drying, etc. Briefly introduce their characteristics: 3.1 scraper discharge centrifuge scraper discharge centrifuge as shown in Figure 4, using the inner rotor wide scraper to rotate the solid at a certain angle Phase, medicinal scraper centrifuge is fully enclosed structure, with automatic control system, residual filter cake removal device as shown in Figure 5, automatic in-place cleaning and in-situ disinfection device as shown in Figure 6, can be installed through the wall as needed ( The art operation part and the driving part are installed separately to achieve pollution-free and aseptic operation. There are deficiencies: due to the unloading method, the solid phase crystal form is broken during the scraping and unloading, and the fine particle solid phase is knotted in the centrifugal force field. When it is a hard filter cake, it is difficult to discharge more thoroughly, especially the filter cake layer deposited on both ends of the rotor. 2.2 The bag-turning centrifuge is shown in Figure 2, and the working part is made of a perforated rotor and The inner rotor is composed of a reversible filter bag. When the inner rotor is unloaded, the inner rotor pushes out the filter cake and the filter bag is turned over to complete the removal of the filter cake as shown in Fig. 7. Its characteristics: completely unloading, without destroying the solid crystal form, in progress Pressure filtration (≤6ban) can be realized when an airtight device is added between the material pipe and the rotor, and the external thermal cycle system can be used to dry the solid phase in the rotor. However, the filter medium (filter bag) is fatigued due to repeated overturning, affecting Service life and contamination caused by solid phase. In addition, the pushing stroke is twice the effective length of the rotor, the structure is slightly large and the low-speed unloading is used to solve the problem of equipment stability. 2.3 Gas discharge centrifugal filter The centrifugal filter and the fluidized bed drying are integrated into a gas discharge centrifugal filter. This type of machine is dried in the machine, which reduces the turnover of the solution, but the suspension to be filtered. The nature requirements have certain limitations. Since today's drying equipment has been greatly developed and improved in terms of cleanliness, high efficiency, energy saving, etc., the economics (including equipment cost and use cost) of using a filter drying machine and selecting a filter and drying split modular device are to be discussed. Another note: it has its superiority under certain conditions. Characteristics and Analysis of 3 Side Filter Centrifugal Filters At the end of the 20th century, China developed a side filter centrifugal filter with theoretical filter-free filtration for the crystallization of raw materials (including amorphous solid phase) (hereinafter referred to as PL centrifuge, such as Figure 8 shows the automatic operation of the three-legged centrifuge, the upper suspension centrifuge, etc., which was widely used in pharmaceuticals at the time. 3.1 The working principle of the side filter centrifugal filter The working principle of the PL centrifuge After the suspension enters the rotor, the solid phase sedimentation is completed simultaneously in the centrifugal force field, and the liquid phase does not pass through the filter cake and directly escapes from the side filter medium to realize liquid/solid separation. The solid phase is pushed in the rotor state after being dried in the rotor. The material device is pushed out as shown in Figure 9. 3.2 Filtration rate of the filter-type centrifugal filter and the analysis of the material adaptability The working principle of the PL centrifuge determines the filtration rate and adaptability of the PL centrifuge. The indicators are better than the filter cake filtration fixed layer centrifuge. The analysis of these two indicators is as follows: 3.2.1 The filtration rate is compared with the filter cake filtration fixed layer centrifuge, and the PL centrifuge is set as a one-time feed. The rate equation for PL centrifuge filtration is given in the pressure field: 4) where: Z-filter medium (r5-r2) h area, the ratio of the two, when η = 1, the two rates are equal, The above formula becomes: 5) When the filter medium is cotton or nylon cloth, Rm=10-9m-1, because the Rm value is small for the simplified comparison, the Rm term is omitted, and the above formula is written as: ...(6) When the actual filter medium area of ​​the PL centrifuge is Z1: Z1=Z, the speed of the PL centrifuge and the filter cake fixed layer centrifuge are equal; Z1>Z, the PL centrifuge rate is greater than the filter cake filtration fixed layer centrifuge speed; Z1 <Z, PL centrifuge rate is less than filter cake filtration fixed layer centrifuge rate. The Z1 value is determined according to factors such as structural tolerance. The Z1 value of the produced PL centrifuge, the calculated Z value and the η value are as shown in Table 1, Z1 which is not designed and designed, and the calculated Z value and η value are shown in Table 2. It can be seen from the η value in the table that under the one-time feeding condition, the rate of the PL centrifuge escaping the liquid phase is more than 120% in the filter cake filtration fixed layer centrifuge rate, and the η value is higher under the continuous feeding condition. Practice has proved that PL650 is as high as 200%. Table 1 Hygienic product PL centrifuge Z1, Z, h value model Z1 Z η PL400 18 14.56 1.23 PL650 24 17.67 1.36 Table 2 Model Z1 Z η P1000 24 19.85 1.20 P1250 28 15.85 1.76 3.2.2 Filter solid particle size Adaptability is determined by the filtration principle and the unloading method. The filter scale of the filter cake is fixed at the production scale. The equivalent diameter of the solid phase particles can be ≥5μm without the filter aid. The reason is the fine particle ratio. The large resistance limits the filtration operation of the thick filter cake and the difficulty of forming a hard filter cake to increase the discharge. For PL centrifuges, it is difficult to discharge unaffected by the particle size (the non-porous surface of the PL centrifuge rotor wall is smooth, and the pressure of the solid phase on the filter medium during the discharge process is negative), as long as it can be filtered. Reach 100% removal. In addition, there is no filter cake filtration in theory, and the rate is not affected by the specific resistance of the filter cake during the filtration process, so that the centrifuge of the fixed layer centrifuge PL has a large adaptability to the solid particle size. The premise of filter-free filtration is to achieve zero leakage theoretically in the filtration process (zero solid phase content in the effluent filtrate). Under zero leakage conditions, can the solid phase particles that can be filtered by the PL centrifuge be smaller than the filter cake? Filtering the particle values ​​defined by the fixed-layer centrifuge and meeting the production scale can be a problem that determines the adaptability of the PL centrifuge. The suspension enters the rotor of the PL centrifuge. The sedimentation force Fc of the particle a in the centrifugal force field is shown in Fig. 10. According to the stokes law: (7) where: ρs-solid phase density; d-particle equivalent diameter; filtrate filtration The driving force of the flow of the filter medium on the side of the plate to the particles Fa:...(8) where: uL-liquid phase flow rate, uL=βpr; β-filter medium characteristic parameter, β=q0/p0 p0-pressure difference between the two sides of the filter medium Q0-the rate at which water passes through the filter medium at p0 differential pressure; pr-the filtration phase pressure at radius r, pr=1/2ρLω2(r2-r02); us-solid phase particle tangential movement speed; solid phase particles In the centrifugal force field, there is only radial velocity, the tangential velocity is zero, and the equation (8) is written as: (8') The critical condition that the particle d does not deposit on the surface of the filter medium in the liquid phase: ...(9) where: f- The coefficient of friction between the surface of the filter medium and the solid phase particles; the amount of liquid passing through the filter medium in the range r to r0: (10) where: the total area of ​​the filter medium in the range from A-r to r0, A = (r-r0) h1Z1; h1-width of filter media surface; solid phase volume percentage in Ф-suspension; 7) Relationship between (8) and (9), Equation (10) is written as: (11) Equation (11) is the amount of liquid phase escaped from the filter medium, and the amount of feed is: (12) Formula (12) V0 = f(r) is expressed as Fig. 11: feeding according to the ab line, that is, the feeding amount is decreased from b to a. Under this condition, the solid phase leakage rate is zero, and the average feeding amount reaches the large value of zui is an ideal state. Due to the difficulty in controlling the decreasing feeding mode, it is abandoned in the application. Actually, the de line above the ac line is used, and the V0 value is in a constant state. The ac line feed amount is expressed in formula (11) as r=r2, and the solid phase leakage is always kept at zero. The penicillin potassium salt is filtered on a PL650 centrifuge as an example: the calculated value is <3> to 3500 L/h, and the feed is calculated. The average amount of 3000 L/h did not measure solid phase leakage. The feed according to the de line indicates that r>r2 in the formula (11), and solid phase leakage occurs. According to the position of the de line, depending on the allowable solid phase leakage and the required injection volume, an aqueous suspension of barium sulfate (d≈2μm) precipitated with cesium hydroxide aqueous solution at -20 ° C was filtered on a PL650 centrifuge. For example, according to r=r2, the V0 value is 430L/h. When the actual feed amount is 810L/h, the solid phase leakage rate is 3.08% of the total solid phase. Taking activated carbon filtration in the production of itaconic acid as an example: the calculated value of V0 is 860L/h under the condition of r=r2, the average feed amount is about 1200L/h in production application, and the solid phase leakage rate is the total amount of solid phase. 1.25%. According to the data in production and experiment, (1) the solid phase zero leakage can be realized by feeding under the ac line; (2) The filtration of the solid equivalent diameter of 2~5μm can be extended by increasing the feeding time (reducing the V0 value) The top phase is filled with the rotor (deposited to the position of r2) or the feed amount is increased within the allowable range of solid phase leakage. It shows that the PL series centrifuge can meet the production scale requirement of solid equivalent diameter ≥ 2μm suspension. When the suspension with a solid diameter of ≥5μm is filtered, due to the inertia of the feed (as shown in Figure 12), the solid phase is deposited in an arc-shaped manner on the surface of the filter medium, and the utilization ratio of the filter surface is 50 to 75% of the total area ( The larger the particle, the closer it is to the lower limit), this factor should be taken into consideration when determining the amount of feed. PL centrifuge has better filtration rate and adaptability than filter cake filtration centrifuge, and has the characteristics of complete discharge, no damage to crystal form, good sealing performance, etc. The comparison list of several indicators is shown in Table 3. Table 3 PL centrifuge and filter cake filter fixed layer centrifuge several main indicators comparison table (same specification comparison) Project model scraper discharge bag unloading PL filtration rate 100% 100% >>120% filterable particle diameter ≥5μm ≥5μm ≥2μm The effect of crystal shape damage remains intact. When the solid phase remains after complete discharge, the solid phase remains >10μm~100% unloading~100% unloading~100% unloading filter medium regenerating and melting mainly as the main flushing Filter media life 100% <100% >>300% Equipment floor area 100% >200% <125% * When the material is unloaded, the relative pressure of the filter medium is negative. 4 Conclusion The raw material medicine filter centrifuge is in the international market today. The company has introduced medicinal horizontal scraper discharge centrifuges, bag-turning centrifuges, etc. to meet GMP and FDA-approved models. Due to the continuous development of pharmaceutical, bioengineering, fine chemical and other industries, new models that meet the requirements will be continuously introduced in the field of centrifugal filtration. The centrifugal filtration and drying machine is a new type of machine, and it is subject to certain pharmaceutical production areas. The conditions are also limited to other models that have been modified according to the characteristics, such as three-legged scraper discharge and bag discharge centrifuge. PL centrifuge is a self-innovated model in China. It has developed two small and medium-sized models, PL400 and PL650. Among them, PL650 has passed the ministry identification and small batch production, and it is separated from penicillin potassium salt and itaconic acid decolorization and deodorization. The liquid-solid separation applications of tea saponin extraction have achieved good results. Practice has proved that the side filtration principle is reliable, and the model manufactured according to this principle can completely replace several kinds of filter cake filtration fixed layer centrifuges recommended by foreign countries. PL centrifuges have relatively low cost of use and manufacturing costs based on the unit yield of the drug substance. Source of information: China Industrial Equipment Network

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