Preparation process of microcrystalline cellulose-colloidal silicon dioxide co-treated substance

Abstract

The invention relates to the technical field of solid preparations, and particularly discloses a preparation process of a microcrystalline cellulose-colloidal silicon dioxide co-treatment substance, which comprises the following steps: mixing chopped wood pulp with hydrochloric acid and purified water, and reacting under ultrasonic and heating conditions to obtain acidic hydrolysis slurry; obtaining a cellulose wet filter cake; a neutral cellulose precipitate is obtained; a surface modification suspension is obtained; primary dry powder is obtained; drying and co-treating to obtain a dried co-treated material; and adding the dried co-treated material, an anti-caking agent and a lubricant into a fluidized bed mixer, and mixing to obtain a final product. The microcrystalline cellulose-colloidal silicon dioxide compound disclosed by the invention adopts a synergistic effect formed by optimizing multiple processes, so that the microcrystalline cellulose-colloidal silicon dioxide compound not only keeps the biocompatibility of cellulose and the characteristics of natural polysaccharide, but also has the thickening, anti-caking and flow improving functions of silicon dioxide. In a plurality of fields such as medicinal tablets, cosmetic suspension and the like, smoother flowability, more stable dispersity and more excellent forming and mechanical properties can be achieved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of solid preparation, and particularly relates to a preparation process of microcrystalline cellulose-colloidal silicon dioxide co-processing product. BACKGROUND

[0002] In many industries such as pharmaceutical, food, and cosmetics, the demand for excipients with good performance is increasing. As a natural polysaccharide excipient, microcrystalline cellulose is widely used in pharmaceutical tabletting and other fields due to its biocompatibility. It can provide certain hardness and formability for the preparation. Colloidal silicon dioxide has the characteristics of thickening, anti-caking, and improving fluidity, and plays an important role in improving the dispersibility and stability of products. Therefore, the preparation of microcrystalline cellulose and colloidal silicon dioxide into a co-processing product is expected to combine the advantages of both and meet the demand for high-performance excipients in many fields.

[0003] However, the existing technology fails to fully exert the synergistic effect between the process steps. The prepared microcrystalline cellulose-colloidal silicon dioxide composite cannot simultaneously well maintain the biocompatibility and natural polysaccharide characteristics of cellulose, and the thickening, anti-caking, and flow improvement functions of silicon dioxide. In practical application fields such as pharmaceutical tabletting, food thickening, and cosmetic suspension, there are problems such as insufficient smoothness of fluidity, unstable dispersibility, and poor formability and mechanical properties, which limit the processability and use effect of the final preparation, and cannot meet the increasing demand for high-performance excipients in the industry. Therefore, it is of great practical significance to develop a new preparation process of microcrystalline cellulose-colloidal silicon dioxide co-processing product.

[0004] To this end, the present application provides a preparation process of microcrystalline cellulose-colloidal silicon dioxide co-processing product to solve the above problems. SUMMARY

[0005] The purpose of the present application is to provide a preparation process of microcrystalline cellulose-colloidal silicon dioxide co-processing product to solve the problems raised in the background.

[0006] To achieve the above-mentioned purpose, the present application provides the following technical scheme:

[0007] A preparation process of microcrystalline cellulose-colloidal silicon dioxide co-processing product, comprising the following steps:

[0008] The chopped wood pulp is mixed with hydrochloric acid and purified water, and reacted under ultrasonic and heating conditions to obtain an acid hydrolysis slurry;

[0009] The acid hydrolysis slurry is separated by vacuum belt filtration to obtain a cellulose wet filter cake;

[0010] washing the cellulose wet cake in a multi-stage washing device with purified water and monitoring pH on-line to neutral, to obtain a neutral cellulose precipitate;

[0011] blending the neutral cellulose precipitate with silane coupling agent modified colloidal silicon dioxide and dispersant, ultrasonic dispersion, to obtain a surface modified suspension;

[0012] atomizing the surface modified suspension through a double-flow nozzle and instantaneously drying in hot air, to obtain a primary dry powder;

[0013] oscillating and sieving the primary dry powder, and vacuum secondary drying and trace anti-caking agent post-processing on qualified powder, to obtain a dry co-processed product;

[0014] adding the dry co-processed product, anti-caking agent and lubricant into a fluidized bed mixer, mixing to obtain a final product.

[0015] Preferably, in step S1, the ultrasonic conditions are 20 kHz, 300 W, the reaction temperature is 80℃, and the reaction time is 2 h.

[0016] Preferably, in step S3, the on-line monitoring of pH is used to control the pH of the washing liquid to 6.8-7.2.

[0017] Preferably, in step S4, the amount of silane coupling agent is 0.5wt% of the total amount of colloidal silicon dioxide.

[0018] Preferably, in step S5, the double-flow nozzle atomization has an inlet air temperature of 180℃ and an outlet air temperature of 90℃.

[0019] Preferably, in step S6, the oscillating sieving uses a 100-200 mesh sieve, and the vacuum drying conditions are 120℃, a vacuum degree less than 50 Pa, and drying for 2 h.

[0020] Preferably, in step S7, the anti-caking agent is 0.2wt% tricalcium phosphate, the lubricant is 0.1wt% magnesium stearate, and the mixing conditions are: 50℃, 50 rpm mixing for 10 min, to improve flowability and powder dispersibility, to obtain a final product.

[0021] Compared with the prior art, the present application has the following beneficial effects:

[0022] (1) The present application uses ultrasonic-assisted acid hydrolysis, which not only accelerates the dissolution of lignin and impurities such as monosaccharides, but also maximizes the retention of the high crystallinity structure of cellulose under mild conditions. The cavitation and shearing effect of ultrasonic waves can make the acid solution penetrate more uniformly into the cellulose cell wall, improve the impurity removal efficiency, and at the same time reduce the mechanical damage to the cellulose chain segment, which is helpful to obtain a cellulose intermediate with higher purity and complete microstructure.

[0023] (2) The multi-stage washing of online pH monitoring in the application ensures that residual acid is completely removed and the surface charge of cellulose is precisely neutralized, creating an ideal interfacial chemical environment for subsequent surface modification. After introducing the silane coupling agent, chemical cross-linking or electrostatic adsorption occurs between colloidal silicon dioxide and the cellulose surface, forming a stable interfacial layer. This interfacial activation not only improves the dispersibility of silicon dioxide on the substrate, but also enhances the compatibility and bonding strength of the two at the molecular level.

[0024] (3) The synergistic effect of the multiple process optimization used in the application enables the microcrystalline cellulose-colloidal silicon dioxide composite to not only maintain the biocompatibility and natural polysaccharide characteristics of cellulose, but also have the thickening, anti-caking, and flow improvement functions of silicon dioxide. In the fields of pharmaceutical tabletting, food thickening, cosmetic suspending, etc., it can exhibit smoother flowability, more stable dispersibility, and more excellent forming and mechanical properties, thereby improving the processability and use effect of the final preparation. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 A preparation process flowchart of a microcrystalline cellulose-colloidal silicon dioxide co-treatment product of the application. DETAILED DESCRIPTION

[0026] The technical solutions in the embodiments of the application will be described clearly and completely below with reference to the drawings in the embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those of ordinary skill in the art without creative labor fall within the scope of protection of the application.

[0027] Example 1:

[0028] Please refer to Figure 1 Fig. 1, which shows a preparation process of a microcrystalline cellulose-colloidal silicon dioxide co-treatment product, uses small-scale preparation for pharmaceutical fillers;

[0029] Acid hydrolysis:

[0030] Raw materials: 10.0 kg of chopped wood pulp, mixed with 12.0 kg of 37% hydrochloric acid and 50.0 kg of purified water;

[0031] Conditions: 80℃, ultrasonic power 300W, reaction time 2.0h;

[0032] After obtaining the slurry, sample it and use high-performance liquid chromatography (HPLC) to determine the dissolved lignin content, which is 98g / L.

[0033] Belt filtration:

[0034] Pump the slurry into a belt filter with a vacuum degree of -0.08MPa;

[0035] The cellulose wet cake 8.2 kg was recovered, and the recovery rate of hydrochloric acid in the filtrate reached 95%.

[0036] Multi-stage washing:

[0037] The cellulose wet cake was washed with 10 L / kg of purified water in each of the three stages;

[0038] The pH was monitored online until the pH of the effluent was 7.0±0.2;

[0039] The neutral cellulose 8.0 kg was obtained, and the residual acid content was less than 0.05 wt%.

[0040] Surface modification slurry:

[0041] The neutral cellulose was blended with colloidal silicon dioxide 4.0 kg (specific surface area 320 m 2 / g), silane coupling agent 0.02 kg, dispersant 0.012 kg, and purified water 100 kg;

[0042] Shearing at 5000 rpm for 3 min and ultrasonic for 5 min to obtain a modified suspension;

[0043] The particle size distribution of the modified suspension was measured by a laser particle size analyzer, and 99% of the particles in the modified suspension had a particle size less than 5 μm.

[0044] Spray drying:

[0045] The inlet air temperature was 180°C, the outlet air temperature was 90°C, and the double-flow nozzle aperture was 50 μm;

[0046] The primary dry powder 11.5 kg was obtained, and the moisture content was 4.8 wt% (determined by Karl Fischer method).

[0047] Oscillating screening and post-processing:

[0048] The screening was 100-200 mesh, and the qualified powder 10.9 kg was obtained;

[0049] Vacuum drying at 120°C, 50 Pa, and 2 h to a moisture content of 2.0 wt%;

[0050] Adding tricalcium phosphate 0.022 kg and magnesium stearate 0.011 kg, and mixing in a fluidized bed at 50°C for 10 min;

[0051] The final product 10.8 kg was obtained.

[0052] From the above, using ultrasonic-assisted acid hydrolysis not only accelerates the dissolution of lignin and impurities such as monosaccharides, but also maximizes the retention of the high crystallinity structure of cellulose under mild conditions. The cavitation and shear effect of ultrasonic waves can make the acid solution more uniformly penetrate into the cellulose cell wall, improve the efficiency of impurity removal, and at the same time reduce the mechanical damage to the cellulose chain segment, which is helpful to obtain cellulose intermediates with higher purity and complete microstructure.

[0053] Example Two:

[0054] Medium-scale preparation for food thickening agent:

[0055] Acid hydrolysis:

[0056] Wood pulp 50 kg, 37% hydrochloric acid 60 kg, purified water 240 kg, 80°C, ultrasonic 300 W, 2.0 h;

[0057] HPLC measured lignin dissolution 102 g / L.

[0058] Belt filtration:

[0059] Vacuum -0.08 MPa; recovered wet cake 41.0 kg.

[0060] Multi-stage washing:

[0061] 3-stage water washing, each 15 L / kg; effluent pH 7.1±0.1; obtained neutral cellulose 40.2 kg.

[0062] Surface modification and slurry preparation:

[0063] Neutral cellulose 40.2 kg, colloidal silicon dioxide 20.1 kg, silane coupling agent 0.1005 kg, dispersant 0.0603 kg, water 480 kg;

[0064] 5000 rpm shear x 3 min, ultrasonic x 5 min; particle size 99% <5.5 μm.

[0065] Spray drying:

[0066] Same conditions; obtained primary dry powder 57.2 kg, moisture 5.1 wt%.

[0067] Oscillating screening and post-treatment:

[0068] Vibration screening 100-200 mesh obtained qualified powder 54.1 kg; dried to 2.1 wt%, added anti-caking agent to obtain product 53.7 kg.

[0069] From the above, the online pH monitoring multistage washing ensures the complete removal of residual acid and the precise neutralization of the cellulose surface charge, creating an ideal interfacial chemical environment for subsequent surface modification. After the introduction of silane coupling agents, chemical cross-linking or electrostatic adsorption occurs between colloidal silica and the cellulose surface, forming a stable interfacial layer. This interfacial activation not only improves the dispersibility of silica on the substrate, but also enhances the compatibility and bonding strength of the two at the molecular level.

[0070] Comparative Example:

[0071] Physical mixing, method: commercially available microcrystalline cellulose and colloidal silica were directly mixed in a dry powder at a ratio of 2:1, without surface modification, without screening reflux, without anti-caking agent post-treatment.

[0072] Comprehensive Example 1, Example 2 and Comparative Example, the data comparison is shown in the following Table 1:

[0073] Table 1

[0074]

[0075] Among them, the data calculation method is as follows:

[0076] Moisture: Karl Fischer (moisture tester);

[0077] Particle size: laser particle size analyzer;

[0078] Specific surface area: BET nitrogen adsorption;

[0079] Hygroscopicity: 75% RH constant temperature box comparison;

[0080] Angle: measured by the tray method;

[0081] Folding strength: measured by USP hardness tester;

[0082] Each index in the table is improved by 10-15% compared with the conventional process, fully verifying the comprehensive technical effect of the scheme in terms of flowability, moisture control and mechanical properties.

[0083] From the above, the double-flow nozzle atomization combined with two-stage precision filtration can form spherical composite microparticles with narrow particle size distribution in the instantaneous drying process, reducing agglomeration and cavitation. The ultrafine particles and suitable pore structure not only ensure high specific surface area, but also maintain sufficient mechanical strength and flowability, providing a stable solid-liquid interface and excellent mechanical response for application in tabletting, thickening or suspension systems.

[0084] Vacuum secondary drying and trace anti-caking agent treatment realize further control of product moisture and improvement of moisture resistance; at the same time, the nanoscale silicon dioxide layer coated on the surface forms a protective film on the micro level, hindering the penetration of environmental moisture. It can be theoretically expected that the co-treatment product can still maintain good fluidity and powder dispersibility under long-term storage and high humidity conditions, significantly reducing the risk of caking and performance degradation.

[0085] The synergistic effect formed by multiple process optimization makes the microcrystalline cellulose-gelatinous silica composite not only maintain the biocompatibility and natural polysaccharide characteristics of cellulose, but also have the thickening, anti-caking and flow improvement functions of silica. In the fields of pharmaceutical tabletting, food thickening, cosmetic suspension, etc., it can play a more smooth fluidity, more stable dispersibility and more excellent forming and mechanical properties, thereby improving the processability and use effect of the final preparation.

[0086] In the description of the specification, the description of the terms "one embodiment", "some embodiments", "example", "specific example" or "some examples" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. In addition, the person skilled in the art can combine and combine the different embodiments or examples described in the specification and the features of the different embodiments or examples without contradiction.

[0087] In the drawings of the embodiments of the present application, only the structures related to the embodiments of the present disclosure are involved, and other structures can be referred to the general design. In the case of no conflict, the same embodiment and different embodiments of the present application can be combined with each other.

[0088] Although the embodiments of the present application have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A process for preparing a microcrystalline cellulose-colloidal silicon dioxide co-processed product, characterized in that: The following steps are involved: The chopped wood pulp is mixed with hydrochloric acid and purified water, and reacted under ultrasonic and heating conditions to obtain an acidic hydrolysis slurry; The acidic hydrolysis slurry is separated by vacuum belt filtration to obtain a cellulose wet cake; washing the cellulose wet cake with purified water in a multi-stage washing device while online monitoring the pH to neutrality to obtain a neutral cellulose precipitate; The neutral cellulose precipitate is mixed with colloidal silica modified with a silane coupling agent and a dispersant, and ultrasonically dispersed to obtain a surface-modified suspension; atomizing the surface-modified suspension through a double-fluid nozzle and drying it instantaneously in hot air to obtain a primary dry powder; The primary dry powder is vibrated and sieved, and the qualified powder is vacuum-dried for a second time and post-treated with a trace amount of an anti-caking agent to obtain a dry co-processed product; The dried co-processed product, anticaking agent and lubricant are added into a fluidized bed mixer and mixed to obtain the final product.

2. The process for preparing a microcrystalline cellulose-colloidal silicon dioxide co-processed product according to claim 1, characterized in that: In step S1, the ultrasonic conditions are 20 kHz, 300 W, the reaction temperature is 80° C., and the reaction time is 2 h.

3. The process for preparing a microcrystalline cellulose-colloidal silicon dioxide co-processed product according to claim 1, characterized in that: In step S3, the online pH monitoring is used to control the pH of the washing liquid at 6.8-7.

2.

4. The process for preparing a microcrystalline cellulose-colloidal silicon dioxide co-processed product according to claim 1, characterized in that: In step S4, the amount of the silane coupling agent used is 0.5 wt % of the total amount of colloidal silica.

5. The process for preparing a microcrystalline cellulose-colloidal silicon dioxide co-processed product according to claim 1, characterized in that: In step S5, the air inlet temperature of the double-fluid nozzle atomization is 180°C, and the air outlet temperature is 90°C.

6. The process for preparing a microcrystalline cellulose-colloidal silicon dioxide co-processed product according to claim 1, characterized in that: In step S6, the vibration screening uses a 100-200 mesh screen, and the vacuum drying conditions are 120° C., a vacuum degree of less than 50 Pa, and drying for 2 hours.

7. The process for preparing a microcrystalline cellulose-colloidal silicon dioxide co-processed product according to claim 1, characterized in that: In step S7, the anti-caking agent is 0.2 wt% tricalcium phosphate, the lubricant is 0.1 wt% magnesium stearate, and the mixing conditions are: 50° C., 50 rpm, and mixing for 10 min to improve fluidity and powder dispersibility to obtain the final product.

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