Preparation method of sodium aluminum silicate powder and application thereof

Abstract

The application discloses a preparation method of sodium aluminosilicate powder and application thereof, and the method comprises the following steps: preparing a sodium silicate solution by using silicic acid and sodium hydroxide, and controlling temperature and co-precipitating with a soluble sodium metaaluminate aqueous solution; adding dilute acid dropwise to neutralize by-product sodium hydroxide in a synchronous manner during the reaction process, so that the precipitation is positively converted; and obtaining amorphous sodium aluminosilicate powder through acid washing + water washing fractional purification, 100-150 DEG C spray drying and segmented grinding. In the application, the soluble sodium metaaluminate is used to replace the traditional difficult-to-dissolve aluminum source of aluminum hydroxide, the synthesis yield is increased to more than 90%, and the raw material cost is significantly reduced; the in-situ neutralization process is combined with fractional acid washing to remove free alkali impurities, the product Na, Al, loose bulk density, drying loss and ignition loss all meet the European Pharmacopoeia pharmaceutical excipient standard, the amorphous structure of the powder is consistent with that of an imported comparative sample, the powder can be used as a solid preparation filler, a flow aid and an anti-caking stabilizer, and has a wide industrial production prospect.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical excipient synthesis technology, specifically relating to a method for preparing sodium aluminum silicate powder and its application in the field of pharmaceutical excipients. Background Technology

[0002] Sodium aluminum silicate is a white, amorphous, fine powder with excellent adsorption, flowability, and chemical stability. It is a core pharmaceutical excipient for oral solid dosage forms and sustained-release preparations. Its functions include improving the flowability of the powder, preventing the raw materials from absorbing moisture and clumping, and enhancing the stability of tablet forming. The world's mainstream pharmaceutical sodium aluminum silicate excipients are mainly produced by companies such as Tomita Pharmaceutical in Japan.

[0003] The current mainstream preparation process in the industry is described in US Patent US005919427A, which uses sodium silicate, sodium hydroxide, and aluminum hydroxide solids as raw materials for co-precipitation to prepare amorphous sodium aluminum silicate. This process has a fatal industrialization defect: aluminum hydroxide has extremely low solubility in alkaline sodium silicate systems, and most of the aluminum source cannot participate in the precipitation reaction, resulting in a product synthesis yield of less than 60%. If high-purity water-soluble aluminum hydroxide is used to improve the solubility, the raw material procurement cost will increase by more than 40%, significantly raising the final selling price of pharmaceutical excipients.

[0004] Existing industrial-grade sodium aluminum silicate is often prepared by using trivalent aluminum salts such as aluminum sulfate and aluminum chloride as aluminum sources, followed by neutralization and precipitation with sodium silicate. However, the aluminum salt system introduces sulfate, chloride ions, and heavy metal impurities. The content of heavy metals such as lead and arsenic exceeds the limits for pharmaceutical excipients, and cannot meet the purity requirements of the European Pharmacopoeia and the Chinese Pharmacopoeia for pharmaceutical inorganic excipients. Therefore, it can only be used in non-pharmaceutical fields such as coatings, rubber, and detergents.

[0005] Therefore, it is necessary to develop a low-cost, high-conversion-rate synthetic route for pharmaceutical-grade sodium aluminum silicate that directly meets pharmacopoeia standards and its applications. Summary of the Invention

[0006] To address the shortcomings of existing aluminum hydroxide sources, such as low yield, high cost, inability of industrial aluminum salts to be used in pharmaceuticals, and the inhibition of product nucleation by-product alkali by precipitation, this invention provides a novel method for preparing pharmaceutical-grade sodium aluminum silicate by co-precipitation of silicate and sodium aluminate. This method includes a complete set of processes such as in-situ neutralization, graded acid washing, temperature-controlled drying, and grinding. The product meets European Pharmacopoeia standards, with a synthesis yield ≥90%, and significantly reduced industrial production costs.

[0007] The reaction equation for sodium aluminum silicate powder provided by this invention is as follows: (1) Pre-synthesis of sodium silicate from silicic acid and sodium hydroxide: ; (2) Sodium aluminate hydration activation: ; (3) Co-precipitation of sodium silicate and activated sodium aluminate (byproduct NaOH): .

[0008] The principle of sodium aluminum silicate powder generation in this invention is as follows: sodium silicate is synthesized in advance by silicic acid and sodium hydroxide, sodium aluminate is hydrated and activated in water, sodium silicate and activated sodium aluminate are co-precipitated to generate sodium aluminum silicate and sodium hydroxide is produced as a byproduct; the acid added simultaneously during the co-precipitation process neutralizes the byproduct sodium hydroxide in real time, consumes the free base in the system, and promotes the reaction equilibrium to shift to the right.

[0009] The method for preparing sodium aluminum silicate powder is as follows: using silicic acid, sodium hydroxide, sodium aluminate and water as raw materials, amorphous sodium aluminum silicate powder is prepared by co-precipitation reaction, solid-liquid separation, washing and purification, drying and grinding. The sodium aluminum silicate powder, as determined by XRD diffraction, exhibits an amorphous structure and meets the specifications for use as a pharmaceutical excipient: Na content of 3.7-6.3 wt%, Al content of 2.7-7.9 wt%, bulk density of 0.25-0.30 g / cm³, loss on drying ≤8.0 wt%, loss on ignition 5.0-11.0 wt%; particle size D50=6-10 μm, D90=10-20 μm, thus qualifying it for use as a pharmaceutical excipient.

[0010] A method for preparing sodium aluminum silicate powder: using silicic acid, sodium hydroxide, sodium aluminate and deionized water as raw materials, a sodium aluminum silicate suspension is generated by co-precipitation reaction, and after solid-liquid separation, washing and purification, drying and grinding, amorphous sodium aluminum silicate powder is obtained.

[0011] Its preparation process includes the following steps: S1. Preparation of sodium silicate mother liquor: Dissolve silicic acid and sodium hydroxide in deionized water, stir at room temperature until completely dissolved, to obtain sodium silicate solution A; S2. Preparation of sodium aluminate solution: Dissolve sodium aluminate in deionized water to prepare a clear solution B; S3 temperature-controlled coprecipitation reaction: Add solution A to the batch reactor and heat to 40-70 ℃ and keep it constant; slowly add solution B dropwise with stirring for 0.5-4 h, and simultaneously add dilute acid to neutralize the reaction byproduct sodium hydroxide in real time throughout the process, controlling the pH at the reaction endpoint to 12±0.5; after the addition is completed, keep it at a constant temperature and stir for 0.5-6 h to mature. S4 Solid-liquid separation and fractional washing: The reaction suspension is separated by centrifugation or vacuum filtration to obtain filter cake; first, wash twice with dilute acid to remove free alkali metal impurities, then wash with deionized water 1 to 8 times until the pH of the supernatant is stable at 10±0.5. S5 Drying and Grinding Purification: After washing, the filter cake is dried at 100-150 ℃ to obtain primary powder; it is then ground for 1-6 h to obtain amorphous sodium aluminum silicate powder.

[0012] Furthermore, In step S1, the molar ratio of sodium hydroxide to silicate is 1.5~2.5; in step S1, the mass ratio of water to solute is 4:1, and the solute is silicate and sodium hydroxide; in step S2, the mass ratio of sodium aluminate to water is 1:10; in step S3, the molar ratio of sodium silicate to sodium aluminate is 1.0-3.0.

[0013] Preferably, in step S5, the washed filter cake is spray-dried at 100-150 °C to obtain primary powder; then it is ground using a ball mill or pulverizer for 1-6 h.

[0014] Preferably, the dilute acid used in step S3 is any one of hydrochloric acid, citric acid, sulfuric acid, and nitric acid.

[0015] Preferably, the stirring rate in step S3 is 300~500 r / min, more preferably 400 r / min; the reaction isothermal temperature is preferably 70 ℃, and the maturation time is 1 h.

[0016] Preferably, the concentration of the dilute acid used in step S3 is 3 mol / L; the pH of the dilute acid used for pickling in step S4 is 4 ± 0.5.

[0017] Preferably, the drying temperature in step S5 is 130 ℃, and the grinding time is 4 h.

[0018] The sodium aluminum silicate powder described above or the sodium aluminum silicate powder prepared by the above preparation method is used as a pharmaceutical excipient in the preparation of pharmaceutical formulations. The pharmaceutical excipient is used as a filler, flow aid and / or anti-caking stabilizer in pharmaceutical formulations.

[0019] Compared with the prior art, the present invention has the following beneficial effects: (1) In view of the problem that aluminum source is difficult to dissolve and has low conversion rate, the present invention uses sodium aluminate, which is completely water soluble, as aluminum source. Aluminum can fully participate in the precipitation reaction and the synthesis yield can reach more than 90%, while the measured yield of traditional aluminum hydroxide process is only 57.2%. At the same time, using silicic acid instead of industrial high-purity sodium silicate as silicon source is beneficial to reducing raw material cost.

[0020] (2) In view of the problem that the by-product alkali of co-precipitation inhibits the nucleation of the product, the present invention simultaneously adds dilute acid in situ to neutralize the by-product sodium hydroxide during the co-precipitation process, consumes the free alkali in the system in real time, promotes the positive shift of the reaction equilibrium, which is conducive to improving the precipitation conversion rate and making the colloidal particles precipitate uniformly and refine the particle size. The loose bulk density, particle size and other indicators of the obtained powder can be controlled without additional classification process.

[0021] (3) In view of the problem of free alkali and heavy metal impurities, the present invention adopts a graded purification process of washing with dilute acid and water, which can remove free sodium impurities, so that the Na and Al content in the dry powder falls within the range of the European Pharmacopoeia, and the heavy metals and residual anions meet the pharmaceutical limits.

[0022] (4) The present invention controls the moisture and particle size of the powder through drying and grinding processes. The resulting product has an amorphous structure and all indicators meet the standards of the European Pharmacopoeia. The test results are consistent with those of the imported comparative sample. It can be used as a substitute for imported pharmaceutical sodium aluminum silicate excipients for filling, flow aid and anti-caking stabilization of solid dosage forms. Attached Figure Description

[0023] Figure 1 The XRD diffraction patterns of Examples 1-5 and the imported comparison sample are shown (amorphous diffuse peaks). Detailed Implementation

[0024] Example 1. A method for preparing sodium aluminum silicate powder: a. Using silicic acid, sodium hydroxide, sodium aluminate, and deionized water as raw materials. (Molar ratio n) Si :n Na Weigh out silicic acid and sodium hydroxide in a ratio of 1:3. Dissolve the weighed silicic acid and sodium hydroxide in deionized water, maintaining a water-to-solute mass ratio of 4:1. Stir at room temperature until the solid is completely dissolved. The silicic acid reacts under alkaline conditions to form a sodium silicate solution, denoted as A.

[0025] b. Weigh out sodium aluminate and dissolve it in deionized water, controlling the mass ratio of sodium aluminate to water to be 1:10. Stir until completely dissolved to obtain a clear sodium aluminate solution, denoted as solution B.

[0026] c. Using coprecipitation synthesis, add solution A prepared in step a to the reaction vessel, turn on heating and stirring, and after the temperature rises to and stabilizes at 70 ºC, maintain this temperature and continue stirring for 30 min.

[0027] d. Under the conditions of maintaining the reactor temperature at 70 ºC and the stirring rate at 400 r / min, solution B (room temperature) was slowly added to the reactor through a constant pressure dropping funnel. The entire addition reaction process lasted for 3 h. At this time, chemical reaction (3) occurred, generating amorphous sodium aluminosilicate. The overall molar ratio of sodium silicate to sodium aluminate was 1:1, and the pH stabilized at 14±0.5 after the addition was completed.

[0028] e. After the addition is complete, continue stirring at 70 ºC for 1 h to promote the growth of sodium aluminosilicate particles. After the reaction is complete, the resulting suspension is subjected to solid-liquid separation to obtain sodium aluminosilicate filter cake, which is the crude sodium aluminosilicate product. The obtained crude product suspension is washed with deionized water 6-8 times until the pH reading of the supernatant stabilizes at 10±0.5. The washed and separated solid is dried in a forced-air dryer at 75 ℃ for 24 h to obtain sodium aluminosilicate powder.

[0029] Example 2. A method for preparing sodium aluminum silicate powder: a. Using silicic acid, sodium hydroxide, sodium aluminate, and deionized water as raw materials. (Molar ratio n) Si :n Na Weigh silicic acid and sodium hydroxide in a ratio of 1:2. Dissolve the weighed silicic acid and sodium hydroxide in deionized water, controlling the mass ratio of water to solute to be 4:1. Stir at room temperature until the solid is completely dissolved. The silicic acid reacts under alkaline conditions to form a sodium silicate solution, which is denoted as solution A.

[0030] b. Weigh out sodium aluminate and dissolve it in deionized water, controlling the mass ratio of sodium aluminate to water to be 1:10. Stir until completely dissolved to obtain a clear sodium aluminate solution, denoted as solution B.

[0031] c. Measure 12 M concentrated hydrochloric acid and dilute it with deionized water to a concentration of 3 M, and denote it as solution C.

[0032] d. Synthesize using the coprecipitation method. Add solution A prepared in step a to the reaction vessel, turn on heating and stirring, and after the temperature rises to and stabilizes at 70 ºC, maintain this temperature and continue stirring for 30 min.

[0033] e. Under the condition of maintaining the reactor temperature at 70 ºC and the stirring rate at 400 r / min, solutions B (room temperature) and C (room temperature) were slowly added to the reactor through a constant pressure dropping funnel, respectively, for a total of 3 h. At this time, chemical reaction (3) occurred, generating amorphous sodium aluminosilicate. The overall molar ratio of sodium silicate to sodium aluminate was 1:1, and the amount of hydrochloric acid added was used to consume most of the sodium hydroxide generated. After the addition was completed, the pH stabilized at 12±0.5.

[0034] f. After the addition is complete, continue stirring at 70 ºC for 1 h to promote the growth of sodium aluminosilicate particles. After the reaction is complete, the resulting suspension is subjected to solid-liquid separation to obtain sodium aluminosilicate filter cake, which is the crude sodium aluminosilicate product. The obtained crude product suspension is washed with deionized water 3-5 times until the pH reading of the supernatant stabilizes at 10±0.5. The washed and separated solid is dried in a forced-air dryer at 105 ℃ for 24 h to obtain sodium aluminosilicate powder.

[0035] Example 3. A method for preparing sodium aluminum silicate powder: a. Using silicic acid, sodium hydroxide, sodium aluminate, and deionized water as raw materials. (Molar ratio n) Si :n Na Weigh out silicic acid and sodium hydroxide in a ratio of 1:2. Dissolve the weighed silicic acid and sodium hydroxide in deionized water, maintaining a water-to-solute mass ratio of 4:1. Stir at room temperature until the solid is completely dissolved. The silicic acid reacts under alkaline conditions to form a sodium silicate solution, denoted as solution A.

[0036] b. Weigh out sodium aluminate and dissolve it in deionized water, controlling the mass ratio of sodium aluminate to water to be 1:10. Stir until completely dissolved to obtain a clear sodium aluminate solution, denoted as solution B.

[0037] c. Measure 12 M concentrated hydrochloric acid and dilute it with deionized water to a concentration of 3 M, and record this as solution C.

[0038] d. Synthesize using the coprecipitation method. Add solution A prepared in step a to the reaction vessel, turn on heating and stirring, and after the temperature rises to and stabilizes at 70 ºC, maintain this temperature and continue stirring for 30 min.

[0039] e. Under the condition of maintaining the reactor temperature at 70 ºC and the stirring rate at 400 r / min, solutions B (room temperature) and C (room temperature) were slowly added to the reactor through a constant pressure dropping funnel, respectively, for a total of 3 h. At this time, chemical reaction (3) occurred, generating amorphous sodium aluminosilicate. The overall molar ratio of sodium silicate to sodium aluminate was 3:2. The amount of hydrochloric acid added was used to consume most of the sodium hydroxide generated, and the pH stabilized at 12±0.5 after the addition was completed.

[0040] f. After the addition is complete, continue stirring at 70 ºC for 1 h to promote the growth of sodium aluminosilicate particles. After the reaction is complete, the resulting suspension is subjected to solid-liquid separation to obtain sodium aluminosilicate filter cake, which is the crude sodium aluminosilicate product. The obtained crude product suspension is washed with deionized water 3-5 times until the pH reading of the supernatant stabilizes at 10±0.5. The washed and separated solid is dried in a forced-air dryer at 105 ℃ for 24 h to obtain sodium aluminosilicate powder.

[0041] Example 4. A method for preparing sodium aluminum silicate powder: a. Using silicic acid, sodium hydroxide, sodium aluminate, and deionized water as raw materials. (Molar ratio n) Si :n Na Weigh out silicic acid and sodium hydroxide in a ratio of 1:2. Dissolve the weighed silicic acid and sodium hydroxide in deionized water, maintaining a water-to-solute mass ratio of 4:1. Stir at room temperature until the solid is completely dissolved. The silicic acid reacts under alkaline conditions to form a sodium silicate solution, denoted as solution A.

[0042] b. Weigh out sodium aluminate and dissolve it in deionized water. Control the mass ratio of sodium aluminate to water to be 1:10 and stir until completely dissolved to obtain a clear sodium aluminate solution, denoted as solution B.

[0043] c. Measure 12 M concentrated hydrochloric acid and dilute it with deionized water to a concentration of 3 M, and record this as solution C.

[0044] d. Synthesize using the coprecipitation method. Add solution A prepared in step a to the reaction vessel, turn on heating and stirring, and after the temperature rises to and stabilizes at 70 ºC, maintain this temperature and continue stirring for 30 min.

[0045] e. Under the condition of maintaining the reactor temperature at 70 ºC and the stirring rate at 400 r / min, solutions B (room temperature) and C (room temperature) were slowly added to the reactor through a constant pressure dropping funnel, respectively, for a total of 3 h. At this time, chemical reaction (3) occurred, generating amorphous sodium aluminosilicate. The overall molar ratio of sodium silicate to sodium aluminate was 2:1. The amount of hydrochloric acid added was used to consume most of the sodium hydroxide generated, and the pH stabilized at 12±0.5 after the addition was completed.

[0046] f. After the addition is complete, continue stirring at 70 ºC for 1 h to promote the growth of sodium aluminosilicate particles. After the reaction is complete, the resulting suspension is subjected to solid-liquid separation to obtain sodium aluminosilicate filter cake, which is the crude sodium aluminosilicate product. The obtained crude product suspension is washed with deionized water 3-5 times until the pH reading of the supernatant stabilizes at 10±0.5. The washed and separated solid is spray-dried at 105 ºC, and the powder is ground in a mechanical grinder for 2 h to obtain sodium aluminosilicate powder.

[0047] Example 5. A method for preparing sodium aluminum silicate powder: a. Using silicic acid, sodium hydroxide, sodium aluminate, and deionized water as raw materials. (Molar ratio n) Si :n Na Weigh out silicic acid and sodium hydroxide in a ratio of 1:2. Dissolve the weighed silicic acid and sodium hydroxide in deionized water, maintaining a water-to-solute mass ratio of 4:1. Stir at room temperature until the solid is completely dissolved. The silicic acid reacts under alkaline conditions to form a sodium silicate solution, denoted as solution A.

[0048] b. Weigh out sodium aluminate and dissolve it in deionized water. Control the mass ratio of sodium aluminate to water to be 1:10 and stir until completely dissolved to obtain a clear sodium aluminate solution, denoted as solution B.

[0049] c. Measure 12 M concentrated hydrochloric acid and dilute it with deionized water to a concentration of 3 M, and record this as solution C.

[0050] d. Synthesize using the coprecipitation method. Add solution A prepared in step a to the reaction vessel, turn on heating and stirring, and after the temperature rises to and stabilizes at 70 ºC, maintain this temperature and continue stirring for 30 min.

[0051] e. Under the condition of maintaining the reactor temperature at 70 ºC and the stirring rate at 400 r / min, solutions B (room temperature) and C (room temperature) were slowly added to the reactor through a constant pressure dropping funnel, respectively, for a total of 3 h. At this time, chemical reaction (3) occurred, generating amorphous sodium aluminosilicate. The overall molar ratio of sodium silicate to sodium aluminate was 2:1. The amount of hydrochloric acid added was used to consume most of the sodium hydroxide generated, and the pH stabilized at 12±0.5 after the addition was completed.

[0052] f. After the addition is complete, continue stirring at 70 ºC for 1 h to promote the growth of sodium aluminosilicate particles. After the reaction is complete, the resulting suspension is subjected to solid-liquid separation to obtain sodium aluminosilicate filter cake, which is the crude sodium aluminosilicate product. The obtained crude product suspension is first washed twice with dilute acid at pH 4±0.5, and then washed 1-2 times with deionized water until the pH reading of the supernatant stabilizes at 10±0.5. The washed and separated solid is spray-dried at 130 ºC, and the powder is ground in a mechanical grinder for 4 h to obtain sodium aluminosilicate powder.

[0053] Test Implementation Example: The present invention conducts performance tests on the sodium aluminum silicate powder prepared in Examples 1-5 and a control sample (Tomita Pharmaceutical Co., Ltd., Japan, 0000066877, hereinafter the same). The test process and results are as follows: 1. XRD diffraction test: XRD diffraction tests were performed on Examples 1-5 and the control sample, and the results are shown in the appendix. Figure 1 As shown, all samples have an amorphous structure.

[0054] The European Pharmacopoeia describes it as a white or off-white, fine, light, amorphous powder.

[0055] The XRD diffraction test results of Examples 1-5 and the control sample all conformed to the requirements of the European Pharmacopoeia.

[0056] 2. Elemental analysis test: Elemental analysis was performed on the sodium aluminum silicate powders prepared in Examples 1-5 and the control samples.

[0057] The European Pharmacopoeia specifies the requirements for Na and Al content in sodium aluminum silicate powder. In its dry powder state, the Na content should be 3.7%–6.3%, and the Al content should be 2.7%–7.9%. The test results are shown in Table 1 below: Table 1. Elemental Analysis Results of Sodium Aluminosilicate The results showed that Examples 3-5 and the control sample all met the requirements of the European Pharmacopoeia.

[0058] 3. Loose bulk density test: The bulk density of the sodium aluminum silicate powders prepared in Examples 1-5 and the control sample was tested, and the results are as follows: The loose bulk density of the control sample was 0.291 g / cm³, while the loose bulk densities of Examples 1-5 were 0.321, 0.259, 0.271, 0.312, and 0.287 g / cm³, respectively. 3 .

[0059] The European Pharmacopoeia specifies a bulk density requirement of 0.25–0.30 g / cm³ for sodium aluminum silicate. 3 .

[0060] The samples prepared in Examples 2, 3, and 5, along with the control samples, all conformed to the requirements of the European Pharmacopoeia.

[0061] 4. Loss on drying and loss on ignition tests: The sodium aluminum silicate powders prepared in Examples 1-5 and the control sample were subjected to drying weight loss and ignition weight loss tests. The results are as follows: The loss on drying and loss on ignition of the control sample were 4.2 wt% and 11.0 wt%, respectively. The loss on drying of Examples 1-5 were 30.97 wt%, 6.0 wt%, 5.8 wt%, 6.7 wt%, and 3.5 wt%, respectively, and the loss on ignition were 35.51 wt%, 15.98 wt%, 16.5 wt%, 16.8 wt%, and 9.6 wt%, respectively.

[0062] The European Pharmacopoeia specifies that for sodium aluminum silicate powder, the loss on drying should not exceed 8.0 wt%, and the loss on ignition should be in the range of 5.0 to 11.0 wt%.

[0063] The samples prepared in Examples 2-5 and the control samples all met the requirements of the European Pharmacopoeia regarding loss on drying; the sample prepared in Example 5 met the requirements of the European Pharmacopoeia regarding loss on ignition.

[0064] 5. BET specific surface area test: The sodium aluminum silicate powders prepared in Examples 1-5 and the control sample were subjected to BET specific surface area tests, and the results are as follows: The specific surface area of ​​the control sample using BET was 37.09 m². 2 / g, the BET specific surface areas of Examples 1-5 were 74.79, 150.44, 96.84, 65.12, and 40.00 m², respectively.2 / g.

[0065] The results showed that the BET specific surface area of ​​Example 5 was very close to that of the control sample.

[0066] 6. Laser particle size analyzer testing: The sodium aluminum silicate powders prepared in Examples 1-5 and the control sample were tested using a laser particle size analyzer. The results are shown in the table below: Table 2. Results of laser particle size analysis of sodium aluminum silicate powder The results showed that the D90, D50, and D10 (µm) results of the sample prepared in Example 5 were basically consistent with those of the control sample.

[0067] To further investigate and verify the optimal process scheme of the present invention, the following comparative experiments were conducted: Comparative Example 1 (i.e., the conventional aluminum hydroxide process described in US005919427A) Raw materials: Modulus 2.0 industrial sodium silicate solution, solid aluminum hydroxide, 30% NaOH; Procedure: Add aluminum hydroxide in batches at 70℃, stir for 2 hours. Only a small amount of solid dissolves. Add NaOH and stir for 4 hours to precipitate. Wash with water 5 times, dry at 105℃ for 24 hours, and grind for 2 hours. Test results: Yield 57.2%; Al content 2.41wt% (below the pharmacopoeia lower limit of 2.7%); loose bulk density 0.335g / cm³ exceeding the standard; D50=52.7μm, indicating coarse particles; Conclusion: Traditional processes result in insufficient aluminum leaching, leading to products that do not meet pharmaceutical standards and low yields.

[0068] Comparative Example 2 (no in-situ neutralizing acid, silicic acid + sodium aluminate raw material system) Using the same raw material ratio as in Example 1, no dilute acid was added during the co-precipitation process, and the final pH was 14.5. Test results: Na content was 10.47 wt% and Al content was 9.83 wt%, exceeding the upper limit; loss on drying was 30.97%, indicating that it is extremely hygroscopic and cannot be used as a pharmaceutical excipient. Conclusion: The lack of an in-situ neutralization step resulted in the alkali byproduct inhibiting precipitation, and the product contained excessive levels of impurities and moisture.

[0069] Comparative Example 3 (aluminum sulfate industrial aluminum source, no acid washing process) Aluminum sulfate was used instead of sodium aluminate, and the rest of the process was the same as in Example 5, except that water washing was used instead of acid washing. Tests revealed: Lead content 28 ppm (pharmaceutical limit ≤10 ppm); Loss on ignition 13.7%, exceeding the upper limit; Anion residue exceeded the limit. Conclusion: Industrial aluminum salts introduce heavy metal impurities and cannot meet the requirements for pharmaceutical use.

[0070] Comparative Example 4 (Spray drying and grinding processes omitted) The raw materials, reaction, and washing process are the same as in Example 5. Drying is carried out at 75°C with forced air, without grinding. Test results: Loss on drying 11.2% > 8%; D90 = 89.4 μm, particle agglomeration; Loose bulk density 0.328 g / cm³ exceeds the standard; Conclusion: Drying and grinding are essential technical features for achieving the required particle size and moisture content in the pharmacopoeia.

[0071] In summary, the sodium aluminum silicate powder prepared in Example 5 meets all the standards of the European Pharmacopoeia and is consistent with the indicators of the comparative sample, and can be used as a pharmaceutical excipient.

[0072] This invention addresses the shortcomings of existing pharmaceutical sodium aluminum silicate processes, which only involve washing and pH adjustment after precipitation, without neutralizing the byproduct sodium hydroxide during co-precipitation. The large amount of free NaOH generated inhibits the nucleation of sodium aluminum silicate colloids, resulting in coarse particles with wide particle size distribution and excessive bulk density, requiring additional complex fractionation processes and increasing energy consumption. The core innovation of this invention lies in the simultaneous addition of dilute acid to neutralize the byproduct NaOH during co-precipitation, consuming free alkali in the system, shifting the reaction equilibrium to the right, improving precipitation conversion rate, and simultaneously controlling the uniform precipitation of colloidal particles, reducing powder particle size. Specifically, the following technical effects are achieved: (1) Innovative raw material route to completely solve the traditional aluminum hydroxide dissolution problem: Sodium aluminate is completely water soluble, and aluminum can participate in precipitation 100%, increasing the yield from the traditional 60% to over 90%; Silicic acid replaces industrial high-purity sodium silicate, significantly reducing raw material costs; (2) In-situ neutralization process greatly improves the physical and chemical properties of the product: the by-product NaOH is consumed in real time, the reaction equilibrium shifts to the right, the particles are small and uniform, and the loose bulk density and particle size index meet the standards, without the need for additional grading; (3) The graded purification process of acid washing and water washing meets the pharmacopoeia requirements: acid washing removes free sodium impurities, the Na and Al content in the dry powder falls precisely within the range of the European Pharmacopoeia, and the heavy metals and residual anions meet the pharmaceutical limits. (4) The whole process is integrated and can be produced continuously on a large scale: the reaction, washing, drying and grinding processes are continuously adapted to the batch reactor, and the equipment modification investment is low; (5) The product has an amorphous structure equivalent to the imported comparison sample: the XRD pattern is completely matched with the Japanese Tomita Pharmaceutical's pharmacopoeia-grade sodium aluminum silicate, and its flowability and anti-caking properties can directly replace the imported excipients.

[0073] Application Examples The sodium aluminum silicate powder prepared in Example 5 of this invention was used as a tablet flow aid: Prescription: 95 parts of ibuprofen raw material, 3 parts of sodium aluminum silicate prepared in Example 5, and 2 parts of microcrystalline cellulose; mix evenly and compress directly into tablets. The tablets have stable hardness and do not clump after 6 months of storage.

[0074] This invention demonstrates that the powder prepared by this invention can completely replace imported pharmaceutical-grade sodium aluminum silicate as a drug filler and anti-caking agent.

Claims

1. A sodium aluminum silicate powder, characterized in that: The reaction equation for the preparation of the sodium aluminum silicate powder is as follows: The method for preparing sodium aluminum silicate powder is as follows: using silicic acid, sodium hydroxide, sodium aluminate and water as raw materials, amorphous sodium aluminum silicate powder is prepared by co-precipitation reaction, solid-liquid separation, washing and purification, drying and grinding. The sodium aluminum silicate powder has an amorphous structure and meets the indicators for use as a pharmaceutical excipient: Na content of 3.7-6.3 wt%, Al content of 2.7-7.9 wt%, bulk density of 0.25-0.30 g / cm³, loss on drying ≤8.0 wt%, loss on ignition 5.0-11.0 wt%; particle size D50=6-10 μm, D90=10-20 μm.

2. A method for preparing the sodium aluminum silicate powder according to claim 1, characterized in that: Using silicic acid, sodium hydroxide, sodium aluminate, and deionized water as raw materials, a sodium aluminum silicate suspension is generated by co-precipitation reaction. After solid-liquid separation, washing and purification, drying, and grinding, amorphous sodium aluminum silicate powder is obtained.

3. The preparation method according to claim 2, characterized in that: The preparation process includes the following steps: S1. Preparation of sodium silicate mother liquor: Dissolve silicic acid and sodium hydroxide in deionized water, stir at room temperature until completely dissolved, to obtain sodium silicate solution A; S2. Preparation of sodium aluminate solution: Dissolve sodium aluminate in deionized water to prepare a clear solution B; S3 temperature-controlled coprecipitation reaction: Add solution A to the batch reactor and heat to 40-70 ℃ and keep it constant; slowly add solution B dropwise with stirring for 0.5-4 h, and simultaneously add dilute acid to neutralize the reaction byproduct sodium hydroxide in real time throughout the process, controlling the pH at the reaction endpoint to 12±0.5; after the addition is completed, keep it at a constant temperature and stir for 0.5-6 h to mature. S4 Solid-liquid separation and fractional washing: The reaction suspension is separated by centrifugation or vacuum filtration to obtain filter cake; first, wash twice with dilute acid to remove free alkali metal impurities, then wash with deionized water 1 to 8 times until the pH of the supernatant is stable at 10±0.

5. S5 Drying and Grinding Purification: After washing, the filter cake is dried at 100-150 ℃ to obtain primary powder; it is then ground for 1-6 h to obtain amorphous sodium aluminum silicate powder.

4. The preparation method according to claim 3, characterized in that: In step S1, the molar ratio of sodium hydroxide to silicate is 1.5~2.5; in step S1, the mass ratio of water to solute is 4:1, and the solute is silicate and sodium hydroxide; in step S2, the mass ratio of sodium aluminate to water is 1:10; in step S3, the molar ratio of sodium silicate to sodium aluminate is 1.0-3.

0.

5. The preparation method according to claim 3, characterized in that: After washing in step S5, the filter cake is spray-dried at 100-150 ℃ to obtain primary powder; then it is ground in a ball mill or pulverizer for 1-6 h.

6. The preparation method according to claim 3, characterized in that: The dilute acid used in step S3 can be any one of hydrochloric acid, citric acid, sulfuric acid, or nitric acid.

7. The preparation method according to claim 3, characterized in that: In step S3, the stirring rate is 300-500 r / min, preferably 400 r / min; the reaction isothermal temperature is preferably 70 ℃, and the maturation time is 1 h.

8. The preparation method according to claim 3, characterized in that: The concentration of the dilute acid used in step S3 is 3 mol / L; the pH of the dilute acid used for pickling in step S4 is 4±0.

5.

9. The preparation method according to claim 3, characterized in that: Step S5: Drying temperature 130 ℃, grinding time 4 h.

10. The application of the sodium aluminum silicate powder according to claim 1 or the sodium aluminum silicate powder prepared by any one of claims 2-9 as a pharmaceutical excipient in the preparation of pharmaceutical formulations, wherein the pharmaceutical excipient is used as a filler, flow aid and / or anti-caking stabilizer in the pharmaceutical formulation.

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