Process for the preparation of pharmaceutical aluminium hydroxide

Abstract

The application discloses a preparation method of medicinal aluminum hydroxide. Industrial aluminum hydroxide powder, industrial sulfuric acid and ammonium bicarbonate are used as raw materials to prepare a sulfuric acid solution and an ammonium bicarbonate solution. Industrial aluminum hydroxide dry powder is reacted with the sulfuric acid solution to generate aluminum sulfate, the aluminum sulfate solution is obtained by dilution, the aluminum hydroxide neutralization liquid is obtained by pre-reaction and reaction of the aluminum sulfate solution and the ammonium bicarbonate solution, the aluminum hydroxide wet material is obtained after filtration, pressure filtration and rinsing, the aluminum hydroxide product is obtained after shearing, spray drying and separation of the aluminum hydroxide wet material. The preparation process is simple, the obtained product does not need to be crushed and sieved, and can meet the conventional medicinal requirements. More importantly, the product has high content and acidifying power, and the quality is very stable. The content and acidifying power of the product are still much higher than the pharmacopoeia standard after being placed at 37 DEG C for 6 months.

Description

Technical Field

[0001] This invention belongs to the field of active pharmaceutical ingredients (APIs) technology, and particularly relates to a method for preparing pharmaceutical-grade aluminum hydroxide. Background Technology

[0002] Aluminum hydroxide, as an antacid raw material, can neutralize excess gastric acid without directly affecting gastric acid secretion, exhibiting a slow but long-lasting antacid effect. In addition, aluminum hydroxide also has adsorption, local hemostatic, and ulcer protection properties. Therefore, pharmaceutical-grade aluminum hydroxide can not only be used as a main ingredient in aluminum hydroxide tablets to relieve various discomfort symptoms such as upper abdominal acid reflux, heartburn, and stomach pain caused by chronic gastritis, gastric ulcers, and reflux esophagitis, but also as an excipient in the preparation of other compound drugs.

[0003] Unlike industrial-grade aluminum hydroxide, pharmaceutical-grade aluminum hydroxide specifically refers to aluminum hydroxide dry gel powder. Therefore, in production, it is necessary to avoid both excessive crystallization of aluminum hydroxide and the formation of a coating on the aluminum hydroxide gel. For example, Chinese invention patent application No. 90105317.1, "Carbon Dioxide Method for Producing Aluminum Hydroxide Gel Series Products," uses sodium aluminate solution as raw material. Carbon dioxide is introduced during the gelation process, followed by aging, washing, solid-liquid separation, and drying to obtain a dry gel product. However, the resulting product has a high sodium oxide content, which does not meet pharmaceutical requirements, and the aging process is too long, significantly reducing production efficiency. Another example is Chinese invention patent application No. 201610786422.5, "A Method for Preparing Pharmaceutical-Grade Aluminum Hydroxide," which uses aluminum sulfate solution and sodium carbonate solution as raw materials. After atomization through an atomizing nozzle, the solution undergoes an impinging flow reaction in a liquid-liquid reactor at a reaction temperature of 40–50°C. Furthermore, it employs a two-stage shear emulsification process to obtain a homogeneous emulsion, which is then spray-dried. The process requires spray liquefaction to complete and also needs to undergo two shear emulsification processes. The spray drying time is also very long, making the whole process overly complicated.

[0004] Therefore, there is a need to further develop a method for preparing pharmaceutical-grade aluminum hydroxide that is simple in process and produces high-quality products. Summary of the Invention

[0005] The purpose of this invention is to optimize the process and improve production efficiency. This invention studies the preparation process of pharmaceutical aluminum hydroxide dry gel.

[0006] The present invention provides a method for preparing pharmaceutical-grade aluminum hydroxide, using industrial aluminum hydroxide powder, industrial sulfuric acid, and ammonium bicarbonate as raw materials to prepare sulfuric acid solution and ammonium bicarbonate solution. The key is that: the above-mentioned industrial aluminum hydroxide powder and the above-mentioned sulfuric acid solution react to generate aluminum sulfate, which is then diluted to obtain an aluminum sulfate solution. The above-mentioned aluminum sulfate solution and the above-mentioned ammonium bicarbonate solution undergo pre-reaction and reaction to obtain an aluminum hydroxide neutralized liquid. After filtration, pressure filtration, and rinsing, wet aluminum hydroxide material is obtained. The above-mentioned wet aluminum hydroxide material is sheared, spray dried, and separated to obtain aluminum hydroxide product.

[0007] Specifically, the mass concentration of the aluminum sulfate solution is 25%–30%, and the mass concentration of the ammonium bicarbonate solution is 30%–40%.

[0008] Furthermore, the aforementioned pre-reaction refers to the flow of aluminum sulfate solution and sodium bicarbonate solution into the spiral feed tube at a flow rate of 1:2 to 3, pre-mixing in the spiral feed tube and controlling the pH value of the solution in the spiral feed tube to 7.5 to 8.5, and then adding the reaction solution to the reaction tank through the spiral feed tube.

[0009] Furthermore, the inner diameter of the aforementioned spiral feed pipe is 1 / 5 to 1 / 3 of the inner diameter of the reaction vessel, and the length is 1 / 3 to 1 / 2 of the height of the reaction vessel. The inner wall of the aforementioned spiral feed pipe is provided with baffles arranged spirally along the direction of liquid flow.

[0010] Specifically, the width of the aforementioned threaded baffle is 1 / 2 to 3 / 5 of the inner diameter of the aforementioned spiral feed tube.

[0011] More specifically, the above reaction involves transferring all the pre-reacted liquid to a reaction vessel, controlling the pressure of the reaction vessel at 0.0125 MPa to 0.025 MPa, the stirring speed at 20 rpm to 30 rpm, and the reaction time at 1 h to 2 h.

[0012] More importantly, the specific process of the spray drying described above involves controlling the temperature inside the drying tower at 100℃~130℃ with uniform temperature distribution, using primary compressed air pressure of 0.25Mpa~0.40Mpa, and using primary compressed air flow rate of 0.8m³ / h. 3 / min~1.2m 3 / min, secondary compressed air pressure is 0.15Mpa~0.35Mpa, secondary compressed air flow rate is 0.6m 3 / min~1.0m 3 / min, the feed flow rate is 0.2kg / min~0.4kg / min.

[0013] More importantly, during the spray drying process, compressed air and / or the exhaust gas recovered from the reaction vessel are used to purge the bottom and sidewalls of the drying tower. The pressure of the purging gas is 0.20 MPa to 0.45 MPa, and the flow rate of the purging gas is 1.6 m³ / s. 3 / min~2.4m 3 / min; the purging angle is 110°~145°.

[0014] Specifically, purging can be continuous or intermittent. Continuous purging means that the purging continues throughout the entire drying process without interruption; intermittent purging means that each purging lasts 8 to 15 seconds, with an interval of 2 to 5 seconds between two purgings.

[0015] In addition, if there are specific requirements for the particle size of aluminum hydroxide, or if special products such as micro powder or ultrafine powder need to be produced, the aluminum hydroxide product obtained after separation can be crushed and sieved.

[0016] Compared with the prior art, the present invention has the following advantages:

[0017] This invention uses industrial aluminum hydroxide powder, industrial sulfuric acid, and ammonium bicarbonate as raw materials. First, the industrial aluminum hydroxide powder is reacted with sulfuric acid solution to generate aluminum sulfate. Then, pharmaceutical-grade aluminum hydroxide dry gel is prepared using aluminum sulfate and ammonium bicarbonate. Specifically, aluminum sulfate and ammonium bicarbonate undergo pre-reaction and reaction to obtain a neutralized aluminum hydroxide solution. After filtration, pressure filtration, and rinsing, a wet aluminum hydroxide material is obtained. This wet aluminum hydroxide material is then sheared, spray-dried, and separated to obtain an aluminum hydroxide product with uniform particle size distribution. The preparation process of this invention is simple, and the obtained product does not require pulverization or sieving, thus meeting conventional pharmaceutical requirements.

[0018] During the production process, a pipeline with built-in spiral baffles is used for premixing and pre-reaction, and the pH range of the pre-reaction is manually controlled to make the reaction more complete and avoid the slagging phenomenon that may occur with aluminum hydroxide gel. The spray drying process effectively prevents large droplets formed due to incomplete drying from adhering to the inner wall of the drying tower, so that the gas and material in the drying tower are mixed more fully and evenly, improving the drying efficiency. It can achieve instantaneous drying within a few seconds, thus making the drying process a continuous process, and the product can be obtained by drying and separating at the same time.

[0019] The dry gel particles prepared by this invention are uniformly and compactly distributed, and the particles are regular large spheres. The prepared product not only has a high content of active ingredients and acid-neutralizing power, but also has very stable quality. After being placed at 37°C for 6 months, the content and acid-neutralizing power of the product are still far higher than the pharmacopoeia standard. Attached Figure Description

[0020] Figure 1 This is the infrared absorption spectrum of sample 1 of the present invention;

[0021] Figure 2 This is the thermogravimetric analysis diagram of sample 1 of the present invention;

[0022] Figure 3 This is the powder X-ray diffraction pattern of sample 1 of the present invention;

[0023] Figure 4 This is a scanning electron microscope image of sample 1 of the present invention at 500 nm;

[0024] Figure 5 This is a scanning electron microscope image of sample 1 of the present invention at 200 nm.

[0025] Figure 6 This is an electron microscope scan of sample 1 of the present invention at 5 μm. Figure 1 ;

[0026] Figure 7 This is an electron microscope scan of sample 1 of the present invention at 5 μm. Figure 2 ;

[0027] Figure 8 This is a scanning electron microscope image of sample 1 of the present invention at 1 μm;

[0028] Figure 9 This is a scanning electron microscope image of the reference sample at 500 nm.

[0029] Figure 10 This is a scanning electron microscope image of the reference sample at 200 nm.

[0030] Figure 11 This is a scanning electron microscope image of the reference sample at 5 μm.

[0031] Figure 12 This is a scanning electron microscope image of the reference sample at 1 μm. Detailed Implementation

[0032] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0033] Unless otherwise specified in the examples, the procedures can be followed according to conventional conditions; unless the manufacturers of the reagents or instruments used are specified, they are all conventional products that can be purchased commercially.

[0034] Examples 1 to 5

[0035] The preparation process for each embodiment is as follows, and the specific parameters in the process are shown in Table 1:

[0036] S1. Dissolving: Dissolve and dilute 500 kg of ammonium bicarbonate with purified water to prepare an ammonium bicarbonate solution with a mass concentration of 30% to 40%, for later use.

[0037] S2. Preparation of aluminum sulfate solution:

[0038] S2-1. Weigh 150 kg of industrial aluminum hydroxide powder for later use;

[0039] S2-2. Dilute industrial concentrated sulfuric acid to a mass concentration of 60% ± 5% and set aside.

[0040] S2-3. Add 400L to 450L of diluted sulfuric acid solution to the reaction vessel, and add the weighed industrial aluminum hydroxide powder in batches while stirring. After the addition is complete, continue stirring and react for 0.5h to 1h. After the reaction is complete, transfer the solution to a dissolving tank, add purified water to dilute the solution to a mass concentration of 25% to 30%, and obtain an aluminum sulfate solution for later use.

[0041] S3. Pre-reaction: The prepared aluminum sulfate solution and ammonium bicarbonate solution are fed into the spiral feed tube at a flow rate of 1:2 to 3. The inner wall of the spiral feed tube is equipped with baffles arranged spirally along the flow direction of the liquid. The inner diameter of the spiral feed tube is 1 / 5 to 1 / 3 of the inner diameter of the reaction tank, and the length is 1 / 3 to 1 / 2 of the height of the reaction tank. The spiral baffles can be continuous or discontinuous.

[0042] The liquid mixture is mixed and pre-reacted in the spiral feed tube. Under the action of the spiral baffle, the collision frequency and intensity between molecules are increased, the relative movement between molecules is accelerated, sulfate ions are prevented from being wrapped on the surface of the generated aluminum hydroxide, and further crystallization of aluminum hydroxide is avoided.

[0043] During the pre-reaction process, the pH value of the pre-reaction process needs to be monitored in real time by an online pH meter installed in the spiral feed pipe. The pH value of the liquid in the pipe is controlled within the range of 7.5 to 8.5 by adding inorganic acid or inorganic base. Finally, all the spare aluminum sulfate solution and ammonium bicarbonate solution are added to the reaction tank through the spiral feed pipe. If the volume of the reaction tank is limited, the reaction can be carried out in multiple batches.

[0044] S4. Reaction: After all the liquid material is transferred into the reaction tank, the reaction is carried out at a stirring speed of 20 rpm to 30 rpm for 1 to 2 hours to obtain a neutralized aluminum hydroxide solution. During the reaction, tail gas is generated. The pressure of the reaction tank is controlled at 0.0125 MPa to 0.025 MPa. Since the main component of the tail gas is carbon dioxide gas, the tail gas generated during the reaction process can be introduced into the tail gas treatment equipment for collection and drying, and then used in the subsequent production process.

[0045] S5. Preparation and shearing of wet aluminum hydroxide:

[0046] S5-1 Preparation of wet aluminum hydroxide: After filtration and pressure filtration and rinsing, the neutralized aluminum hydroxide solution is used to obtain wet aluminum hydroxide in block form. The filtration method is plate and frame filtration or centrifugal filtration, and the pressure filtration method is rotary drum filtration. During the rotary drum filtration process, purified water is used for the first rinsing and / or the second rinsing. The backflush gas pressure and flow rate are controlled during the pressure filtration process to control the moisture content of the obtained wet aluminum hydroxide in block form to be controlled at 20% to 30%.

[0047] S5-2, Shearing of wet aluminum hydroxide: The wet aluminum hydroxide block after pressure filtration is sheared by a shear pump to obtain a homogeneous aluminum hydroxide liquid, and the liquid is transferred to a storage tank.

[0048] S6. Spray drying:

[0049] S6-1. Preheating: Set the temperature at the bottom of the drying tower to 100℃~130℃. When the temperature difference between the set value at the bottom of the tower and the maximum and minimum bottom temperature values ​​does not exceed 5℃, it indicates that the temperature distribution inside the tower is uniform.

[0050] S6-2, Drying:

[0051] The liquid material in the storage tank is fed into the sprayer via a screw feeder, and sprayed under the action of primary and secondary compressed air. The pressure of the primary and secondary compressed air is controlled at 0.25 MPa to 0.40 MPa, and the flow rate of the primary compressed air is 0.8 m³ / s. 3 / min~1.2m 3 / min, secondary compressed air pressure is 0.15Mpa~0.35Mpa, secondary compressed air flow rate is 0.6m 3 / min~1.0m 3 / min, the feed flow rate is 0.2kg / min~0.4kg / min;

[0052] Simultaneously, compressed air and / or the exhaust gas recovered in step S4 are used to purge the bottom and sidewalls of the drying tower. The pressure of the purging gas is controlled at 0.15 MPa to 0.35 MPa, and the flow rate of the purging gas is 1.6 m³ / min. 3 / min~2.4m 3 / min, the purging angle is 110°~145°, the purging is continuous or intermittent, continuous purging means that the purging continues throughout the entire drying process without interruption, and the purging time and interval of each intermittent purging are shown in Table 1;

[0053] After spray drying, the aluminum hydroxide product with uniform particle size distribution is obtained by separation in the separator of the drying tower. This product is aluminum hydroxide dry gel, denoted as samples 1 to 5. The particle size distribution and quality analysis of samples 1 to 5 are determined.

[0054] If there are specific requirements for the particle size of aluminum hydroxide, or if special products such as micro powder or ultrafine powder need to be produced, it can be further crushed and sieved.

[0055] Table 1: Specific process parameters for each embodiment

[0056]

[0057] Continued from Table 1: Specific process parameters for each embodiment

[0058]

[0059] Continued from Table 1: Specific process parameters for each embodiment

[0060]

[0061] Comparative Example 1

[0062] The implementation method is the same as in Example 1, except that "S3, pre-reaction" is not performed. Instead, the liquid is directly transferred into the reaction tank to react and obtain control sample 1.

[0063] Comparative Example 2

[0064] The implementation method is the same as in Example 1, except that in the "S1, Dissolution" step, ammonium bicarbonate is not used. Instead, 670 kg of sodium carbonate is dissolved in purified water and the sodium carbonate solution is diluted for later use and subsequent preparation to obtain reference product 2.

[0065] Comparative Example 3

[0066] Comparative Example 2 of the implementation method does not use ammonium bicarbonate. Instead, 670 kg of sodium carbonate is dissolved and diluted with purified water to form a sodium carbonate solution for later use. The difference is that "S3, pre-reaction" is not performed. The solution is directly transferred to the reaction tank for reaction to obtain control product 3.

[0067] Comparative Example 4

[0068] The implementation method is the same as in Example 1, except that when performing "S6, spray drying", compressed air and / or the exhaust gas recovered in step S4 are not used to purge the bottom and side walls of the drying tower, thus obtaining control sample 4.

[0069] Analysis and Testing

[0070] I. Structural Confirmation Analysis

[0071] Sample 1 of Example 1 was subjected to infrared spectroscopy, thermogravimetric analysis, powder X-ray diffraction and electron microscopy analysis, and compared with the standard (i.e. reference sample).

[0072] (1) Infrared spectroscopy analysis

[0073] Take an appropriate amount of the test sample and mix it with KBr in a certain proportion, then compress it into tablets using a tablet compressor. Refer to the relevant provisions of General Chapter 0402 of the 2020 edition of the Chinese Pharmacopoeia (Part IV) for parameter settings and infrared spectrum determination. The test results are shown in Table 2 and [Table data missing]. Figure 1 .

[0074] Table 2: Results of Infrared Absorption Spectroscopy Measurement

[0075]

[0076] As can be seen from the results in Table 2, the characteristic absorptions of the functional groups of Sample 1 and the reference sample are consistent.

[0077] (2) Thermogravimetric analysis

[0078] Take an appropriate amount of the test sample, accurately weigh it, place it in an alumina crucible, compact it, and then place it in the furnace. Refer to the relevant provisions of General Chapter 0661 of the 2020 edition of the Chinese Pharmacopoeia (Part IV) to set the parameters, record and compare the TG spectra of aluminum hydroxide and the reference sample. The test results for sample 1 are shown in [reference needed]. Figure 2 .

[0079] Depend on Figure 2 As can be seen, the thermogravimetric analysis (TG) curve of sample 1 shows that it begins to lose weight at room temperature, and the weight loss rate at 800℃ is -37.2700%, which is caused by sample decomposition. The experimental phenomenon is consistent with that of the reference sample.

[0080] (3) Powder X-ray diffraction

[0081] Take an appropriate amount of the test sample on the zero background rack, flatten it with a glass slide, and place it inside the instrument. Refer to the relevant provisions of General Chapter 0451 of the 2020 edition of the Chinese Pharmacopoeia (Part IV) to set the parameters, record and compare the powder X-ray diffraction patterns of aluminum hydroxide and the reference sample. The test results for sample 1 are shown in [reference needed]. Figure 3 .

[0082] Depend on Figure 3 The results show that neither Sample 1 nor the reference sample has a specific powder diffraction pattern, indicating that both samples are amorphous solids. Furthermore, the diffraction peak positions of Sample 1 and the reference sample are basically the same, suggesting that Sample 1 is an aluminum hydroxide dry gel.

[0083] (4) Electron microscopy analysis

[0084] Sample 1 was adhered to the sample stage with conductive adhesive, and the test positions were marked. The sample stage was placed on the sample carrier, a vacuum was drawn, and the electron beam was turned on. Selective microscopic morphology testing was performed. Photos were taken and stored. The test results at different scales are shown in [reference needed]. Figures 4 to 12 .

[0085] Depend on Figures 4 to 12The results show that the dry powder colloid of the present invention exhibits a uniform and dense particle arrangement under a 500nm or 200nm scale; under a 5μm scale, it can be clearly seen that the colloid particles of the present invention are very regular spherical and the particles are larger than those of the reference sample.

[0086] II. Particle Size Distribution Test

[0087] Weigh 100g of the sample to be tested and sieve it using pharmacopoeia sieves of 80 mesh, 60 mesh, 40 mesh, and 20 mesh. The sample mass between 40 mesh and 60 mesh should exceed 60% of the total sample mass, and the sample mass below 80 mesh should be less than 10% of the total sample mass. No particles larger than 20 mesh should be present. The test results are shown in Table 3.

[0088] Table 3: Particle size distribution of the samples to be tested

[0089] Sample to be tested Below 80 mesh 80 mesh-60 mesh 60 mesh-40 mesh 40 mesh-20 mesh More than 20 mesh Sample 1 9.0％ 12.3％ 68.0％ 10.7％ 0.0％ Sample 2 8.2％ 11.5％ 67.5％ 12.8％ 0.0％ Sample 3 8.8％ 9.6％ 66.1％ 15.5％ 0.0％ Sample 4 7.1％ 10.3％ 69.8％ 12.8％ 0.0％ Sample 5 7.9％ 9.8％ 65.3％ 17.0％ 0.0％ Reference Standard 1 11.8％ 5.5％ 61.2％ 21.5％ 0.0％ Reference Standard 2 7.6％ 9.5％ 57.3％ 25.6％ 0.0％ Reference Standard 3 8.6％ 6.3％ 53.3％ 30.3％ 1.5％ Reference Standard 4 5.4％ 7.6％ 52.9％ 32.6％ 1.5％

[0090] As shown in Table 3, the particle size distribution of the samples prepared by this invention is mostly concentrated in the range of 40-60 mesh, reaching over 65%, with no large particles larger than 20 mesh, and the content of fine powder below 80 mesh is less than 9%. This indicates that the aluminum hydroxide dry gel particles prepared by this invention are uniform and have good applicability. In particular, the samples to be tested in this invention are directly tested from the spray-dried samples without further crushing and sieving. This shows that this method can simplify the conventional production process. If there are no special requirements for the particle size of the product, a uniformly distributed dry gel product can be obtained without crushing and sieving.

[0091] A small number of large particles larger than 20 mesh were detected in reference standards 3 and 4, indicating that the selection of suitable raw materials, pre-reaction processes, and purging during the reaction process collectively affect the particle size distribution of the product. Specifically, the purging process can form an air wall on the inner wall of the drying tower, preventing larger droplets from incomplete spray drying from adhering to the inner wall. It can also change the airflow direction within the drying tower, resulting in more thorough and uniform mixing of gas and material, improving drying efficiency. Furthermore, the multi-angle airflow impact helps form more uniform particles.

[0092] II. Quality Analysis

[0093] According to the analytical method for aluminum hydroxide described on page 935 of the 2020 edition (Part II) of the Chinese Pharmacopoeia, the content, acid-neutralizing power, alkali metal carbonates, sulfates and heavy metals of the sample were determined, and the results are shown in Table 4.

[0094] Table 4: Summary Table of Quality Analysis Data of Samples to be Tested

[0095]

[0096] As shown in Table 4, the content and acid-neutralizing power of the samples prepared by this invention are much higher than those of the reference standard and also much higher than the pharmacopoeia standard.

[0097] III. Stability Assessment

[0098] The samples were placed at 37℃ for 1 month, 3 months, and 6 months, and the content and acid-neutralizing capacity were determined. The results were compared and analyzed with the data from the initial stage of the study in Table 3. The results are shown in Tables 5 and 6.

[0099] Table 5: Summary of Content Data for Stability Study of Samples to be Tested

[0100]

[0101] Table 6: Summary of acid-generating power data for stability studies of the samples to be tested

[0102]

[0103] As can be seen from Tables 5 and 6, after six months of accelerated stability testing, the content and acid-neutralizing power of the samples prepared by this invention still meet the pharmacopoeia standards, and the decrease is not significant. This indicates that the samples prepared by this invention not only have high initial content and acid-neutralizing power, but also have more stable product quality.

Claims

1. A method for preparing pharmaceutical-grade aluminum hydroxide, comprising using industrial aluminum hydroxide powder, industrial sulfuric acid, and ammonium bicarbonate as raw materials to prepare sulfuric acid solution and ammonium bicarbonate solution, characterized in that: The industrial aluminum hydroxide powder reacts with the sulfuric acid solution to produce aluminum sulfate, which is then diluted to obtain an aluminum sulfate solution. The aluminum sulfate solution and the ammonium bicarbonate solution undergo a pre-reaction and reaction to obtain an aluminum hydroxide neutralized liquid. After filtration, pressure filtration and rinsing, wet aluminum hydroxide material is obtained. The wet aluminum hydroxide material is then sheared, spray-dried, and separated to obtain the aluminum hydroxide product. The pre-reaction refers to the flow of aluminum sulfate solution and ammonium bicarbonate solution into the spiral feed tube at a flow rate of 1:2 to 3, pre-mixing in the spiral feed tube and controlling the pH value of the solution in the spiral feed tube to 7.5 to 8.5, and then adding the reaction solution to the reaction tank through the spiral feed tube; The reaction involves transferring all the pre-reacted liquid to a reaction tank, controlling the pressure of the reaction tank at 0.0125 MPa to 0.025 MPa, the stirring speed at 20 rpm to 30 rpm, and the reaction time at 1 h to 2 h. During the spray drying process, compressed air and / or the exhaust gas recovered from the reaction vessel are used to purge the bottom and sidewalls of the drying tower. The pressure of the purging gas is 0.20 MPa to 0.45 MPa, and the flow rate of the purging gas is 1.6 m³ / s. 3 / min~2.4 m 3 / min; the purging angle is 110°~145°; The inner diameter of the spiral feed pipe is 1 / 5 to 1 / 3 of the inner diameter of the reaction tank, and the length is 1 / 3 to 1 / 2 of the height of the reaction tank. The inner wall of the spiral feed pipe is provided with baffles arranged spirally along the direction of liquid flow.

2. The method for preparing pharmaceutical-grade aluminum hydroxide according to claim 1, characterized in that: The aluminum sulfate solution has a mass concentration of 25%–30%, and the ammonium bicarbonate solution has a mass concentration of 30%–40%.

3. The method for preparing pharmaceutical-grade aluminum hydroxide according to claim 1, characterized in that: The width of the spiral baffle is 1 / 2 to 3 / 5 of the inner diameter of the spiral feed tube.

4. The method for preparing pharmaceutical-grade aluminum hydroxide according to claim 1, characterized in that: The specific process of spray drying is as follows: the temperature inside the drying tower is controlled at 100℃~130℃ with uniform temperature distribution; the primary compressed air pressure is 0.25 MPa~0.40 MPa; and the primary compressed air flow rate is 0.8 m³ / s. 3 / min~1.2 m 3 / min, secondary compressed air pressure is 0.15 MPa to 0.35 MPa, and secondary compressed air flow rate is 0.6 m³ / min. 3 / min~1.0 m 3 The feed flow rate is 0.2 kg / min to 0.4 kg / min.

5. The method for preparing pharmaceutical-grade aluminum hydroxide according to claim 1, characterized in that: The purging can be continuous or intermittent. Continuous purging means that the purging continues throughout the entire drying process without interruption. Intermittent purging means that each purging lasts for 8 to 15 seconds, with an interval of 2 to 5 seconds between two purgings.

6. The method for preparing pharmaceutical-grade aluminum hydroxide according to claim 1, characterized in that: The aluminum hydroxide product obtained after separation is crushed and sieved.

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