Preparation method of lactose and microcrystalline cellulose blend

Abstract

The invention relates to the technical field of filling agents, and particularly discloses a lactose and microcrystalline cellulose blend preparation method which comprises the following steps: sieving lactose through a 80-mesh sieve, and removing impurities through ultrasonic assistance; the preparation method comprises the following steps: carrying out surface modification on microcrystalline cellulose by using a silane coupling agent, adding 183L of purified water into a mixing tank, stirring, preheating lactose to 50-60 DEG C, adding, dissolving, adding microcrystalline cellulose, and stirring until the microcrystalline cellulose is swelled; lactose is added and stirred to be uniform, and mixed liquid is obtained; high-temperature air inlet is set for the spray dryer for spray drying. And screening and mixing the dried granules, and packaging the granules with PE (polyethylene) bags, wherein each bag is 20Kg. According to the method, the process is simplified, the energy consumption is reduced, the production efficiency and the product quality are improved, the method is suitable for the pharmaceutical preparation industry, the tedious step that process water is firstly heated and then cooled in the traditional process is omitted, the energy consumption is reduced, the production period is effectively shortened, the consumption of water resources is reduced, and the overall production efficiency is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of fillers, and particularly relates to a method for preparing a copolymer of lactose and microcrystalline cellulose. Background Art

[0002] Lactose and microcrystalline cellulose (MCC) are core fillers in the production of tablet drugs, each with unique physical and chemical properties. Lactose, which exists in various forms such as α-lactose monohydrate, anhydrous β-lactose and spray-dried lactose, all exhibit excellent fluidity and moderate compressibility. In contrast, microcrystalline cellulose is slightly inferior to lactose in fluidity due to its large aspect ratio, but its excellent compressibility makes it an important ingredient in pharmaceutical preparations. The premixed excipient formed by combining lactose and MCC through specific technology can give full play to the synergistic advantages of the two and improve the overall performance of pharmaceutical preparations.

[0003] Lactose-microcrystalline cellulose composite excipient, as a co-processed spray-dried compound, is mainly composed of 75% lactose monohydrate and 25% cellulose, and is white or nearly white odorless powder. Its composition ratio (73-77% lactose monohydrate and 23-27% microcrystalline cellulose) has been carefully designed to meet the direct tableting process requirements of pharmaceutical preparations. This composite excipient not only combines the filler and binder properties of lactose and MCC, but also brings significant economic benefits and practical performance.

[0004] However, the existing method for preparing lactose-microcrystalline cellulose co-processed products has many shortcomings:

[0005] The treatment of process water is cumbersome: the traditional process requires that the process water be heated with steam and then cooled to 50°C. This process is not only time-consuming but also energy-intensive, increasing production costs.

[0006] The energy consumption of preparing colloid by emulsifier is high: although the slurry is made into a uniform colloid by emulsifier, the product quality can be ensured, but the power consumption of emulsifier is high and the process is extremely time-consuming, which further increases the energy consumption and production cost.

[0007] High water consumption and evaporation energy consumption: In the traditional process, the ratio of microcrystalline cellulose, lactose and process water is as high as 1:2.73.2:8.59, which not only leads to a large amount of water resource consumption, but also requires a lot of energy in the water evaporation process, reducing production efficiency.

[0008] Low efficiency of spray drying: Since the traditional process uses 100-120℃ for spray drying, this temperature is only slightly higher than the boiling point of water, resulting in a low water evaporation rate and low production efficiency, which cannot meet the high-efficiency requirements of modern drug production. Summary of the invention

[0009] The object of the present invention is to provide a method for preparing a copolymer of lactose and microcrystalline cellulose to solve the problems raised in the above background technology.

[0010] To achieve the above object, the present invention provides the following technical solutions:

[0011] A method for preparing a lactose-microcrystalline cellulose copolymer comprises the following steps:

[0012] Step 1, weighing lactose and microcrystalline cellulose, passing the lactose through an 80-mesh sieve for later use, using an ultrasonic-assisted screening device to ultrasonically vibrate lactose particles to remove fine impurities and promote the dispersion of lactose particles;

[0013] The microcrystalline cellulose was slightly surface modified by using a silane coupling agent to improve its compatibility and dispersibility with lactose;

[0014] Step 2: Add 183L of purified water required by the process into the batching tank, start stirring at 30-50Hz, preheat the lactose in a microwave preheater, set the temperature to 50°C-60°C, preheat for 2-5 minutes, add 31Kg of preheated lactose, stir for 30-60min until the lactose is completely dissolved, then add 50.26Kg of microcrystalline cellulose, and stir for 4h until swelling;

[0015] Step 3, continue to add 119 kg of lactose, stir for 10 to 30 minutes until uniform, and obtain a mixed liquid, wherein the ratio of microcrystalline cellulose: lactose: process water is 1:2.7 to 3.2:2.8 to 4;

[0016] Step 4: Set the inlet air temperature of the spray dryer to 175±25°C, turn on the air inlet and heating system, set the blower frequency to 45±5Hz, and the outlet air temperature to 95°C; when the inlet air temperature is heated to the set value, set the feed pump flow rate to 3.0-4.0L / min, adjust the feed system to the automatic gear of the associated feed pump flow rate, and turn on the feed switch to start spray drying production;

[0017] Step 5: Transfer the screened particles in the mobile silo to the double cone mixer at a speed of 15 Hz and mix for 30 minutes.

[0018] Step 6: Collect the materials in PE bags for inner packaging, 20Kg / bag.

[0019] Step seven: affix a label containing the production batch number, production date, and expiration date to each bag of product, and upload all information to the electronic information storage backend.

[0020] Preferably, the models of the ultrasonic assisted screening equipment include but are not limited to USV-20K ultrasonic assisted screening equipment and AS-80 automatic screening machine, and the silane coupling agent includes but is not limited to A-174 and A-171.

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

[0022] The cumbersome steps of heating and then cooling the process water in the traditional process are omitted. Purified water is directly used, and lactose is preheated by microwave, which not only simplifies the operation process and greatly reduces energy consumption, but also effectively shortens the production cycle. At the same time, the process of preparing colloids using an emulsifier is avoided. This not only reduces the power consumption of the equipment, but also greatly shortens the process time and reduces production costs. The ratio of microcrystalline cellulose, lactose and process water is optimized and adjusted to 1:2.73.2:2.84, which significantly reduces the water consumption. The consumption of water resources is reduced, and the energy consumption required for subsequent water evaporation is reduced, thereby improving the overall production efficiency. At the same time, fine impurities in lactose are removed, the dispersibility of lactose particles is improved, and the compatibility of microcrystalline cellulose and lactose is enhanced. These measures jointly improve the product quality and stability of composite excipients and provide better fillers for pharmaceutical preparations. DETAILED DESCRIPTION

[0023] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0024] Embodiment 1:

[0025] A method for preparing a lactose-microcrystalline cellulose copolymer comprises the following steps:

[0026] Step 1: Raw material preparation and pretreatment

[0027] The ultrasonic assisted screening equipment model USV-20K was used, with the vibration frequency set to 28kHz and the amplitude set to 10μm, which effectively removed fine impurities in the lactose and promoted uniform dispersion of particles.

[0028] Microwave preheating: Use MW-100 microwave preheater, place lactose in it, set the temperature to 50°C, and use the rapid heating characteristics of microwaves to evenly preheat the lactose to the required temperature within 3 minutes, reducing the preheating time and avoiding local overheating.

[0029] A-171 silane coupling agent was used to perform surface treatment at 0.5% of the weight of microcrystalline cellulose, and the mixture was mixed at a speed of 1000 rpm for 10 minutes in a high-speed mixer to improve the compatibility and dispersibility of microcrystalline cellulose and lactose.

[0030] Step 2: Dissolution and swelling

[0031] Add 183L of purified water into the batching tank, turn on the agitator, set the frequency to 45Hz, and ensure the uniformity of the water flow.

[0032] Lactose dissolution: Add 31 kg of preheated lactose, use the temperature control system to maintain the temperature at 55°C, and stir for 45 minutes until the lactose is completely dissolved.

[0033] Add in stages: Add microcrystalline cellulose twice, 25.13 kg each time, stirring for 2 hours after each addition, for a total of 4 hours to ensure that the microcrystalline cellulose is fully swollen.

[0034] Step 3: Mixing and homogenization

[0035] Continue to add lactose: After the microcrystalline cellulose is completely swollen, cool to room temperature and add the remaining 119 kg of lactose.

[0036] High-speed shear mixing: Use a HS-2000 high-speed shear mixer, set the speed to 2500 rpm, mix for 15 minutes to ensure that the lactose and microcrystalline cellulose are fully mixed and uniform, and obtain a mixed liquid 1.

[0037] Step 4: Spray Drying

[0038] Spray dryer settings: Set the air inlet temperature to 180°C, allow the fluctuation range to be ±5°C, turn on the air inlet and heating system, and use PID temperature control technology to automatically adjust.

[0039] Air supply parameters: The fan frequency is set to 45Hz, the allowable adjustment range is ±2Hz, and the air outlet temperature is maintained at 95℃.

[0040] Spray Drying Operation:

[0041] Automatic feeding: After the inlet air temperature reaches the set value, start the feeding pump and set the flow rate to 3.5L / min. The allowable fluctuation range is ±0.2L / min.

[0042] Atomization and drying: Use a pressure nozzle, adjust the atomization pressure to 2.2MPa, start spray drying, continuously monitor the outlet air temperature and material status, and adjust the parameters in time to maintain the best drying effect.

[0043] Step 5: Post-processing and blending

[0044] Screening and mixing: The dried particles are screened through a vibrating screen to remove oversized or undersized particles. The screened particles are transferred to a double cone mixer, set at a speed of 15 Hz, and mixed for 30 minutes to ensure product uniformity.

[0045] Step 6: Packaging and dehumidification

[0046] Automatic packaging: Use AP-20 automatic packaging machine to pack the evenly mixed particles into PE bags, 20kg per bag, and automatically weigh and seal them.

[0047] Dehumidification treatment: Add high-efficiency desiccant packs into the packaging to ensure the stability of the product during long-term storage.

[0048] Step 7: Smart labeling and traceability

[0049] Labeling system: A smart label containing production batch number, production date, expiration date, batch number and other information is affixed to each bag of product.

[0050] Electronic traceability: Upload all information to the electronic traceability system to achieve full traceability of the product, including key links such as raw material source, production process, and quality inspection.

[0051] Implementation 2:

[0052] 150 kg of lactose was weighed and sieved using an automatic sieving machine of model AS-80 with a sieve of 80 mesh. The material on the sieve was used for subsequent dissolution, and the material under the sieve was used as fine powder for later use.

[0053] 50 kg of microcrystalline cellulose was surface-modified using A-174 type silane coupling agent at 0.3% of the weight of the microcrystalline cellulose, and mixed at 800 rpm for 20 minutes using a high-speed mixer to improve its compatibility and dispersibility with lactose.

[0054] Step 2: Dissolution and swelling

[0055] Add 160L of purified water to the batching tank, turn on the agitator and set the frequency to 40Hz.

[0056] Add the sieved lactose (about 120 kg) into the batching tank, maintain constant temperature, and stir for 40 minutes until the lactose is completely dissolved.

[0057] The modified microcrystalline cellulose was added to the lactose solution and the stirring was continued for 3 hours to allow the microcrystalline cellulose to fully swell.

[0058] Step 3: Blending and Adjusting

[0059] The remaining lactose (about 30 kg) and the sieved fine powder lactose were added, and mixed at a speed of 1200 rpm for 20 minutes using a high-efficiency mixer to ensure that all ingredients were evenly mixed to obtain a mixed liquid.

[0060] Step 4: Spray Drying

[0061] Spray Dryer Settings:

[0062] Set the inlet air temperature to 200℃, and the allowable fluctuation range is ±10℃.

[0063] The fan frequency was set to 50 Hz and the air outlet temperature was maintained at 100 °C.

[0064] Spray Drying Operation:

[0065] Turn on the feed pump and set the flow rate to 4.0L / min.

[0066] Use a pressure nozzle, adjust the atomization pressure to 2.5 MPa, and start spray drying.

[0067] During the drying process, the air supply temperature and material flow rate are adjusted in time according to the air outlet temperature and material status to ensure the drying effect.

[0068] Step 5: Post-processing and screening

[0069] The dried particles were sieved through a 40-mesh vibrating screen to remove particles that were too large or too small, and to obtain particles that met the requirements.

[0070] Step 6: Mixing and packaging

[0071] The sieved particles were transferred to a double cone mixer, the speed was set to 20 Hz, and mixed for 40 minutes to ensure product uniformity.

[0072] Use an automatic packaging machine to pack the evenly mixed particles into PE bags, 25 kg per bag, and automatically weigh and seal them.

[0073] Step 7: Quality Inspection and Traceability

[0074] Each batch of products is subjected to quality inspection, including appearance, particle size distribution, moisture content and other indicators.

[0075] Affix a label containing production batch number, production date, expiration date, quality inspection report and other information to each bag of product.

[0076] Upload all product information to the enterprise electronic traceability system to achieve full traceability of the product.

[0077] Implementation three:

[0078] Step 1: Weigh lactose and microcrystalline cellulose, the total amount of lactose is 150kg. First, pass the lactose through an 80-mesh sieve, weigh the material on the sieve and dissolve it in 10L of purified water at 60°C, and weigh the material under the sieve for later use. Slightly modify the surface of microcrystalline cellulose and use an appropriate amount of silane coupling agent for surface treatment to improve its compatibility and dispersibility with lactose. In this example, the total amount of microcrystalline cellulose is 50.26kg.

[0079] Step 2: Dissolution and swelling

[0080] Add the purified water required for the process to the batching tank, a total of 183L, and start stirring at a frequency of 30Hz. Preheat the lactose in a microwave preheater, set the temperature to 50°C, and preheat for 3 minutes. After preheating, add 30kg of lactose to the batching tank at a ratio of 15-25g lactose / 100g purified water, and stir for 30 minutes until the lactose is completely dissolved. Subsequently, add 50.26kg of processed microcrystalline cellulose and continue stirring for 4 hours until the microcrystalline cellulose is fully swollen. Step 3: Mix evenly

[0081] Continue to add the remaining lactose (the total amount is 150 kg minus the amount of dissolved lactose) to the batching tank and stir for 15 minutes until all ingredients are evenly mixed to obtain a mixed liquid. At this time, the ratio of microcrystalline cellulose, lactose and process water is about 1:2.7:2.8.

[0082] Step 4: Spray Drying

[0083] Set the spray dryer inlet temperature to 175°C, turn on the air inlet and heating system, set the blower frequency to 45Hz, and the air outlet temperature to 95°C. After the inlet temperature is heated to the set value, set the feed pump flow rate to 3.5L / min, and adjust the feed system to the automatic gear for the associated feed pump flow rate. Turn on the feed switch to start spray drying production until all the mixed liquid is completely dry.

[0084] Step 5: Sieving and Mixing

[0085] The granules obtained by spray drying were screened by a sieving machine with a mesh size of 40. The screened granules were collected in a mobile silo and transported to a double cone mixer. The speed of the double cone mixer was set to 15 Hz and the mixing time was set to 30 min to ensure the uniformity of the granules.

[0086] Step 6: Packaging and labeling

[0087] The mixed particles are packed in PE bags, each weighing 20kg. Each bag of product is labeled with the production batch number, production date, expiration date and other information, and all the information is uploaded to the electronic information storage backend for easy traceability and management.

[0088] The invention improves product quality, production efficiency and market competitiveness by optimizing various links in the preparation process of lactose and microcrystalline cellulose copolymer, including raw material pretreatment, dissolution and swelling, mixing and adjustment, spray drying, post-treatment and screening, mixing and packaging, quality inspection and traceability.

[0089] It will be appreciated that in the development of any actual implementation, as in any engineering or design project, numerous implementation-specific decisions may be made. Such a development effort may be complex and time-consuming, but will be a routine task of design, fabrication, and production for those of ordinary skill having the benefit of this disclosure without undue experimentation.

[0090] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A method for preparing a copolymer of lactose and microcrystalline cellulose, characterized in that: The following steps are involved: Step 1, weighing lactose and microcrystalline cellulose, passing the lactose through an 80-mesh sieve for later use, using an ultrasonic-assisted screening device to ultrasonically vibrate lactose particles to remove fine impurities and promote the dispersion of lactose particles; The microcrystalline cellulose was slightly surface modified by using a silane coupling agent to improve its compatibility and dispersibility with lactose; Step 2: Add 183L of purified water required by the process into the batching tank, start stirring at 30-50Hz, preheat the lactose in a microwave preheater, set the temperature to 50°C-60°C, preheat for 2-5 minutes, add 31Kg of preheated lactose, stir for 30-60min until the lactose is completely dissolved, then add 50.26Kg of microcrystalline cellulose, and stir for 4h until swelling; Step 3, continue to add 119 kg of lactose, stir for 10 to 30 minutes until uniform, and obtain a mixed liquid, wherein the ratio of microcrystalline cellulose: lactose: process water is 1:2.7 to 3.2:2.8 to 4; Step 4: Set the inlet air temperature of the spray dryer to 175±25°C, turn on the air inlet and heating system, set the blower frequency to 45±5Hz, and the outlet air temperature to 95°C; when the inlet air temperature is heated to the set value, set the feed pump flow rate to 3.0-4.0L / min, adjust the feed system to the automatic gear of the associated feed pump flow rate, and turn on the feed switch to start spray drying production; Step 5: Transfer the screened particles in the mobile silo to the double cone mixer at a speed of 15 Hz and mix for 30 minutes. Step 6: Collect the materials in PE bags for inner packaging, 20Kg / bag. Step seven: affix a label containing the production batch number, production date, and expiration date to each bag of product, and upload all information to the electronic information storage backend.

2. The method for preparing a lactose and microcrystalline cellulose copolymer according to claim 1, characterized in that: The models of the ultrasonic assisted screening equipment include but are not limited to USV-20K ultrasonic assisted screening equipment and AS-80 automatic screening machine, and the silane coupling agent includes but is not limited to A-174 and A-171.