An apparatus and method for preparing composite-embedded α / β anhydrous lactose microparticles

Abstract

The present invention relates to an apparatus and method for preparing composite embedded structure α / β anhydrous lactose microparticles, belonging to the technical field of lactose preparation. It can systematically adjust parameters such as temperature, air pressure, and flow rate before and after spray drying. By changing the temperature in the precursor solution stage, the recrystallization behavior of lactose is systematically regulated to obtain the required anhydrous β-lactose, and α-lactose is coated on the surface of β-lactose in the spray drying and fluidized bed stages to maintain the stability of the entire lactose composite particles, and at the same time, composite particles with uniform properties and adjustable proportions are obtained. During the whole process, the ratio of α-lactose / β-lactose, the particle size distribution, and the water content of the particles can be regulated to adjust its dissolution rate, solubility, and compressibility. Moreover, it has stable properties and uniform quality.

Description

Technical Field

[0001] The present invention relates to an apparatus and method for preparing composite-embedded α / β anhydrous lactose microparticles, belonging to the technical field of lactose preparation. Background Art

[0002] α-lactose and β-lactose are two isomers with very similar chemical structures but different molecular configurations. Specifically, the difference between them lies in the positions of their hydroxyl groups. Both α-lactose and β-lactose are composed of a disaccharide molecule called lactose, which is formed by a glucose molecule and a galactose molecule bonded through a 1-4 bond. Their molecular formulas are both C12H22O11, but their structures are slightly different. In α-lactose, the hydroxyl group is located below the first carbon atom (C1) of glucose, while in β-lactose, the hydroxyl group is located above the first carbon atom of glucose. This small structural difference can lead to differences in their metabolism and biological activities in vivo, such as different hydrolysis rates in the intestine.

[0003] At the same time, although the physical states and chemical structures of α-lactose and β-lactose are very similar, there are significant differences in their solubility and compressibility. Generally speaking, the solubility of β-lactose is slightly lower than that of α-lactose, which is caused by their different molecular configurations. In water, there are significant differences in the solubility of α-lactose and β-lactose. This means that at the same temperature and pressure, for the same amount of lactose, its crystal form has a great influence on the dissolution amount and dissolution rate. At the same time, in the pharmaceutical and pharmaceutical industries, the compressibility of drugs is a very important property. Some studies have shown that there are differences in the crystal morphology of α-lactose and β-lactose, which may lead to differences in their compressibility. Therefore, in the pharmaceutical process, according to specific application requirements and drug characteristics, it may be necessary to adjust the formulation and process conditions according to the solubility differences between α-lactose and β-lactose. However, in a normal temperature and pressure environment, monohydrate β-lactose easily absorbs surrounding water molecules at room temperature, which will cause it to lose its crystallinity and be prone to moisture absorption during storage. This results in problems such as unstable crystal form, uncertain crystal form ratio, and inability to control the crystal form ratio in lactose production.

[0004] In view of the above-mentioned defects, the present invention aims to create an apparatus and method for preparing composite-embedded α / β anhydrous lactose microparticles, making it more valuable for industrial utilization. Summary of the Invention

[0005] To solve the above technical problems, the object of the present invention is to provide an apparatus and method for preparing composite-embedded α / β anhydrous lactose microparticles. It can systematically adjust parameters such as temperature, air pressure, and flow rate before and after spray drying. By changing the temperature in the pre-liquid stage, the recrystallization behavior of lactose is systematically regulated to obtain the desired anhydrous β-lactose, and α-lactose is coated on the surface of β-lactose during the spray drying and fluidized bed stages to maintain the stability of the entire lactose composite particles, while obtaining composite particles with uniform properties and adjustable proportions. During the whole process, the ratio of α-lactose / β-lactose, the particle size distribution, and the water content of the particles can be regulated to adjust their dissolution rate, solubility, and compressibility. Moreover, they have stable properties and uniform quality.

[0006] An apparatus for preparing composite-embedded α / β anhydrous lactose microparticles of the present invention includes a dissolution and recrystallization control unit and a control unit. The outlet end of the dissolution and recrystallization control unit is connected in series through a spray drying unit and a fluidized bed unit. The fluidized bed unit is connected to the inlet end of the collection unit. A circulating air duct is also provided on the collection unit. The control unit is electrically and signal-connected to the dissolution and recrystallization control unit, the spray drying unit, the fluidized bed unit, the collection unit, and the circulating air duct respectively.

[0007] Further, the dissolution and recrystallization control unit includes a heating container, in which a layered filter screen and a programmed stirring device are provided. A dissolution and recrystallization program control system is also provided at the bottom of the heating container. The layered filter screen has adjustable pore size and shape. The dissolution / recrystallization program temperature control device is a programmable logic controller.

[0008] Further, the spray drying unit includes an atomization chamber, in which a temperature controller is installed in the inner cavity. A nozzle is also installed at the top of the atomization chamber. A pressure controller and a flow controller are provided on the nozzle. An atomizer is installed at the outlet end of the nozzle. The nozzle has adjustable spray droplet size and speed. The diameter range of the nozzle is 0.5 mm to 5 mm, and the spray pressure range of the nozzle is 0.5 MPa to 5 Mpa.

[0009] Further, the fluidized bed unit includes a fluidized bed. The bottom of the fluidized bed is connected in series through a heating system, a fan, and an air inlet. An air outlet is also provided at the top of the fluidized bed. The heating system has adjustable temperature and flow rate. The temperature range of the heating system is 40°C to 200°C, and the air flow velocity range of the air inlet is 0.1 m / s to 5 m / s.

[0010] Further, the collection unit includes a filter, a static precipitator is connected to the rear end of the filter, the tail end of the static precipitator communicates with the collector, a discharge port is arranged at the outlet of the collector, the filtration efficiency range of the filter is 80% to 99.9%, and the electrostatic field strength range of the static precipitator is 2 kV / m to 20 kV / m; the filter and the static precipitator of the collection unit adopt adjustable filtration efficiency and electrostatic field strength.

[0011] Further, the circulating air duct includes an air duct, and an air valve and a wind speed controller are arranged on the air duct.

[0012] Further, the control unit includes a programmable logic controller and a human-machine interface, which are used for real-time monitoring and adjustment of the working parameters of the spray drying unit, the fluidized bed unit, the collection unit and the circulating air duct.

[0013] Further, the programmable logic controller and the human-machine interface of the control unit can real-time monitor, record and adjust each working parameter.

[0014] A method for preparing composite embedded structure α / β anhydrous lactose particles, and the specific preparation steps are as follows:

[0015] (1) Dissolve lactose in an appropriate amount of water to obtain a lactose solution; the concentration range of the lactose solution is 1% to 30% to effectively control the formation of spray-dried particles.

[0016] (2) Heat the lactose solution to 80 - 85 °C, transfer it to the dissolution and recrystallization control unit, stir and filter in a heating container, and use the temperature change and the screening effect of the layered filter screen to form high-purity β-lactose crystals in the lactose solution, and control its particle size and shape.

[0017] (3) Transfer the lactose solution containing β-lactose crystals to the spray drying unit, atomize it into fine droplets through a nozzle, and adjust the temperature with a temperature controller in the atomization chamber to crystallize and embed α-lactose on the surface of the β-lactose crystals to form composite embedded structure α / β anhydrous lactose particles.

[0018] (4) Transfer the particles after spray drying to the fluidized bed unit, and use a heating system and a blower in the fluidized bed to provide a constant temperature and air flow, so that the particles are quickly dried and formed to obtain spherical α / β anhydrous lactose particles.

[0019] (5) Transfer the particles at the outlet of the fluidized bed to the collection unit, separate and collect the particles with a filter and a static precipitator, and remove excess gas and impurities, store the collected particles in the collector, or output them through the discharge port.

[0020] By means of the above solution, the present invention has at least the following advantages:

[0021] The equipment for preparing the composite-embedded structure α / β anhydrous lactose particles of the present invention can systematically adjust parameters such as temperature, air pressure, and flow rate before and after spray drying. By changing the temperature in the pre-liquid stage, the recrystallization behavior of lactose is systematically regulated to obtain the required anhydrous β-lactose. And during the spray drying and fluidized bed stages, α-lactose is coated on the surface of β-lactose to maintain the stability of the entire lactose composite particles, while obtaining composite particles with uniform properties and adjustable proportions. During the whole process, the ratio of α-lactose / β-lactose, the particle size distribution, and the water content of the particles can all be regulated, so as to adjust its dissolution rate, solubility, and compressibility. Moreover, the properties are stable and the quality is uniform.

[0022] The above description is only an overview of the technical solution of the present invention. In order to be able to understand the technical means of the present invention more clearly and to be implemented in accordance with the content of the specification, the following takes the preferred embodiments of the present invention and combines with the drawings to describe in detail as follows. Brief Description of the Drawings

[0023] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required to be used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show a certain embodiment of the present invention, and therefore should not be regarded as a limitation of the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings.

[0024] Figure 1 is a schematic structural diagram of the equipment for preparing the composite-embedded structure α / β anhydrous lactose particles of the present invention;

[0025] Figure 2 is a solubility trend diagram of different configurations of lactose in water with temperature change;

[0026] Figure 3 、 4 is an electron micrograph of the lactose particles prepared in Example 1 of the present invention;

[0027] Figure 5 、 6 is an electron micrograph of the lactose particles prepared in Example 2 of the present invention;

[0028] Figure 7 、 8 is an electron micrograph of the lactose particles prepared in Example 3 of the present invention. Detailed Embodiments

[0029] The following combines with the drawings and embodiments to further describe in detail the specific embodiments of the present invention. The following embodiments are used to illustrate the present invention, but are not used to limit the scope of the present invention.

[0030] See Figure 1, An apparatus for preparing composite-embedded α / β anhydrous lactose microparticles according to a preferred embodiment of the present invention includes a dissolution and recrystallization control unit 1 and a control unit 6. The outlet end of the dissolution and recrystallization control unit 1 is connected in series through a spray drying unit 2 and a fluidized bed unit 3. The inlet end of the fluidized bed unit 3 is connected to a collection unit 4. A circulating air duct 5 is further provided on the collection unit 4. The control unit 6 is electrically connected to the dissolution and recrystallization control unit 1, the spray drying unit 2, the fluidized bed unit 3, the collection unit 4, and the circulating air duct 5 by electrical signals;

[0031] The dissolution and recrystallization control unit 1 includes a heating container (1-1). A layered filter screen 1-2 and a programmed stirring device 1-3 are arranged in the heating container 1-1. A dissolution and recrystallization program control system 1-4 is further provided at the bottom of the heating container 1-1. Based on the solubility curves of α-lactose / β-lactose with temperature changes and the solubility differences between α / β at different temperatures, the temperature change in the dissolution and recrystallization control unit 1 is adjusted through the temperature control system program, so as to release high-purity β-lactose crystals before spray drying, and the appropriate crystal grain size and shape are screened based on the layered screen;

[0032] The layered filter screen 1-3 has adjustable pore sizes and shapes to screen the required crystal nuclei; the dissolution / recrystallization program temperature control device 1-4 is a programmable logic controller PLC, which can monitor, record, and adjust each temperature parameter in real time according to the established program to ensure that the content of crystalline β-lactose in the precursor suspension fed into unit 2 during the production process is greater than 90%, so as to ensure the high uniformity and quality stability of the spray-dried microparticles of the α / β anhydrous lactose composite-embedded structure during the production process;

[0033] The spray drying unit 2 includes an atomization chamber 2-2. A temperature controller 2-4 is installed in the inner cavity of the atomization chamber 2-2. A nozzle 2-1 is further installed at the top of the atomization chamber 2-2. A pressure controller 2-5 and a flow controller 2-6 are provided on the nozzle 2-1. An atomizer 2-3 is installed at the outlet end of the nozzle 2-1 to control the atomization, temperature, pressure, and flow rate of the lactose solution, generate uniform spray droplets, and form a composite-embedded microparticle structure in which α-lactose crystallizes on the surface of the screened particles and embeds β-lactose;

[0034] The nozzle 2-1 has adjustable spray droplet sizes and speeds; the diameter of the nozzle 2-1 ranges from 0.5 mm to 5 mm to achieve spray droplet diameters between 1 μm and 100 μm; the spray pressure ranges from 0.5 MPa to 5 MPa to effectively control the spray droplet sizes;

[0035] The fluidized bed unit 3 includes a fluidized bed 3-1. The bottom of the fluidized bed 3-1 is connected in a communicating manner through a heating system 3-2, a blower 3-3, and an air inlet 3-4. An air outlet 3-5 is further provided at the top of the fluidized bed 3-1, which is used to achieve the rapid drying of the spray droplets and the formation of anhydrous lactose spherical microparticles.

[0036] The temperature range of the heating system 3-2 is from 40°C to 200°C to optimize the formation and drying effect of the spray-dried microparticles of the α / β anhydrous lactose composite embedding structure; the concentration range of the lactose solution is from 1% to 30% to effectively control the formation of the spray-dried microparticles; the air flow velocity range is from 0.1 m / s to 5 m / s to maintain a constant air flow environment inside the system.

[0037] The heating system 3-2 adopts adjustable temperature and flow rate to optimize the formation and drying effect of the spray-dried microparticles of the α / β anhydrous lactose composite embedding structure.

[0038] The collection unit 4 includes a filter 4-1. A static precipitator 4-2 is connected to the rear end of the filter 4-1. The tail end of the static precipitator 4-2 is in communication with a collector 4-3. A discharge port 4-4 is provided at the outlet of the collector, which is used to separate and collect the spray-dried microparticles of the α / β anhydrous lactose composite embedding structure.

[0039] The filtration efficiency range of the filter 4-1 is from 80% to 99.9% to achieve the efficient collection and separation of the spray-dried microparticles of the α / β anhydrous lactose composite embedding structure; the electrostatic field strength range of the static precipitator 4-2 is from 2 kV / m to 20 kV / m to achieve the efficient separation of the spray-dried microparticles.

[0040] The filter 4-1 and the static precipitator 4-2 of the collection unit 4 adopt adjustable filtration efficiency and electrostatic field strength to achieve the efficient collection and separation of the spray-dried microparticles of the α / β anhydrous lactose composite embedding structure.

[0041] The circulating air duct 5 includes an air duct 5-1. An air valve 5-2 and an air velocity controller 5-3 are provided on the air duct 5-1, which are used to adjust the air flow.

[0042] The air valve 5-2 and the air velocity controller 5-3 of the circulating air duct 5 can achieve precise adjustment of the air flow to maintain a constant air flow environment inside the system.

[0043] The control unit 6 includes a programmable logic controller PLC6-1 and a human-machine interface HMI6-2, which are used to monitor and adjust the working parameters of the spray drying unit 1, the fluidized bed unit 2, the collection unit 3, and the circulating air duct 4 in real time.

[0044] The programmable logic controller PLC6-1 and the human-machine interface HMI6-2 of the control unit 6 can monitor, record, and adjust each working parameter in real time to ensure the quality stability of the spray-dried particles of the α / β anhydrous lactose composite embedding structure during the production process;

[0045] A method for preparing α / β anhydrous lactose particles with a composite embedding structure, and the specific preparation steps are as follows:

[0046] 1. Dissolve lactose in an appropriate amount of water to obtain a lactose solution. The concentration range of the lactose solution is 1% to 30% to achieve effective control over the formation of spray-dried particles.

[0047] 2. Heat the lactose solution to 80 - 85 °C, transfer it to the dissolution and recrystallization control unit 1, stir and filter in the heating container 1-1, and use the temperature change and the screening effect of the layered filter screen 1-2 to form high-purity β-lactose crystals in the lactose solution and control their particle size and shape. The layered filter screen 1-2 has adjustable pore sizes and shapes to screen the required crystal nuclei. The programmable logic controller of the dissolution and recrystallization program temperature control device 1-4 can monitor, record, and adjust each temperature parameter in real time according to the established program to ensure that the content of crystalline β-lactose in the precursor suspension fed into unit 2 during the production process is greater than 90%, so as to ensure the high uniformity and quality stability of the spray-dried particles of the α / β anhydrous lactose composite embedding structure during the production process.

[0048] 3. Transfer the lactose solution containing β-lactose crystals to the spray-drying unit 2, atomize it into fine droplets through the nozzle 2-1, and adjust the temperature in the atomization chamber 2-2 with the temperature controller 2-4 so that α-lactose crystallizes and embeds on the surface of the β-lactose crystals to form α / β anhydrous lactose particles with a composite embedding structure. The nozzle 2-1 has adjustable spray droplet sizes and speeds. The diameter range of the nozzle 2-1 is 0.5 mm to 5 mm to achieve a spray droplet diameter between 1 μm and 100 μm. The spray pressure range is 0.5 MPa to 5 MPa to achieve effective control over the spray droplet size. The temperature range of the atomization chamber 2-2 is 40 °C to 200 °C to optimize the forming and drying effects of the spray-dried particles of the α / β anhydrous lactose composite embedding structure.

[0049] 4. Transfer the spray-dried particles to the fluidized bed unit 3, and use the heating system 3-2 and the blower 3-3 in the fluidized bed 3-1 to provide a constant temperature and air flow to quickly dry and form the particles to obtain spherical α / β anhydrous lactose particles. The temperature range of the heating system 3-2 is 40 °C to 200 °C to optimize the forming and drying effects of the spray-dried particles of the α / β anhydrous lactose composite embedding structure. The air flow velocity range is 0.1 m / s to 5 m / s to maintain a constant air flow environment inside the system.

[0050] 5. Transfer the fine particles at the fluidized bed outlet to the collection unit 4. Use the filter 4-1 and the electrostatic precipitator 4-2 to separate and collect the fine particles, and remove the excess gas and impurities. Store the collected fine particles in the collector 4-3 or output them through the discharge port 4-4. The filtration efficiency range of the filter 4-1 is 80% to 99.9% to achieve efficient collection and separation of the spray-dried fine particles of the α / β anhydrous lactose composite embedding structure. The electrostatic field strength range of the electrostatic precipitator 4-2 is 2 kV / m to 20 kV / m to achieve efficient separation of the spray-dried fine particles.

[0051] During the whole preparation process, use the control unit 6 to monitor and adjust the working parameters of each unit in real time, such as temperature, pressure, flow rate, filtration efficiency, electrostatic field strength, etc., to ensure the quality and stability of the product.

[0052] Example 1

[0053] 1. Dissolve lactose in an appropriate amount of water to obtain a lactose solution. The concentration of the lactose solution is 10% to achieve effective control of the formation of the spray-dried fine particles.

[0054] 2. Heat the lactose solution to 80 °C and transfer it to the dissolution and recrystallization control unit 1. Stir and filter in the heating container 1-1. Utilize the temperature change and the screening effect of the layered filter screen 1-2 to form high-purity β-lactose crystals in the lactose solution and control their particle size and shape. The layered filter screen 1-2 has adjustable pore size and shape to screen the required crystal nuclei. The dissolution and recrystallization program temperature control device 1-4 is a programmable logic controller, which can monitor, record and adjust each temperature parameter in real time according to the established program to ensure that the content of crystal β-lactose in the precursor suspension fed into the unit 2 during the production process is greater than 90%, so as to ensure the high uniformity and quality stability of the spray-dried fine particles of the α / β anhydrous lactose composite embedding structure during the production process.

[0055] 3. Transfer the lactose solution containing β-lactose crystals to the spray-drying unit 2. Atomize it into fine droplets through the nozzle 2-1, and use the temperature controller 2-4 to adjust the temperature in the atomization chamber 2-2 to make α-lactose crystallize and embed on the surface of the β-lactose crystals to form composite embedding structure α / β anhydrous lactose fine particles. The nozzle 2-1 has adjustable spray droplet size and speed. The diameter of the nozzle 2-1 is 5 mm to achieve a spray droplet diameter of 500 μm. The spray pressure is 0.5 MPa to achieve effective control of the spray droplet size. The temperature of the atomization chamber 2-2 is 40 °C to optimize the forming and drying effects of the spray-dried fine particles of the α / β anhydrous lactose composite embedding structure.

[0056] 4. Transfer the spray-dried particles to the fluidized bed unit 3. In the fluidized bed 3-1, use the heating system 3-2 and the blower 3-3 to provide a constant temperature and air flow, so that the particles are quickly dried and formed to obtain spherical α / β anhydrous lactose particles. The temperature of the heating system 3-2 is 40 °C to optimize the forming and drying effects of the spray-dried particles of the α / β anhydrous lactose composite embedding structure. The air flow rate is 0.1 m / s to maintain a constant air flow environment inside the system.

[0057] 5. Transfer the particles at the outlet of the fluidized bed to the collection unit 4. Use the filter 4-1 and the electrostatic precipitator 4-2 to separate and collect the particles, and remove the excess gas and impurities. Store the collected particles in the collector 4-3 or output them through the discharge port 4-4. The filtration efficiency of the filter 4-1 is 90% to achieve the efficient collection and separation of the spray-dried particles of the α / β anhydrous lactose composite embedding structure. The electrostatic field strength range of the electrostatic precipitator 4-2 is 10 kV / m to achieve the efficient separation of the spray-dried particles.

[0058] See Figure 3 and Figure 4 , and the finally obtained anhydrous lactose particles have a particle size of 180 microns, a relatively fast dissolution rate, a solubility of 30 g / 100 mL, and an average tablet hardness of 37 N.

[0059] During the whole preparation process, use the control unit 6 to monitor and adjust the working parameters of each unit in real time, such as temperature, pressure, flow rate, filtration efficiency, electrostatic field strength, etc., to ensure the quality and stability of the product.

[0060] Example 2

[0061] 1. Dissolve lactose in an appropriate amount of water to obtain a lactose solution. The concentration of the lactose solution is 25% to effectively control the formation of the spray-dried particles.

[0062] 2. Heat the lactose solution to 83 °C and transfer it to the dissolution and recrystallization control unit 1. Stir and filter in the heating container 1-1. Utilize the temperature change and the screening effect of the layered filter screen 1-2 to form high-purity β-lactose crystals in the lactose solution and control their particle size and shape. The layered filter screen 1-2 has adjustable pore sizes and shapes to screen the required crystal nuclei. The dissolution and recrystallization program temperature control device 1-4 is a programmable logic controller, which can monitor, record, and adjust each temperature parameter in real time according to the established program to ensure that the content of crystal β-lactose in the precursor suspension fed into the unit 2 during the production process is greater than 90%, so as to ensure the high uniformity and quality stability of the spray-dried particles of the α / β anhydrous lactose composite embedding structure during the production process.

[0063] 3. Transfer the lactose solution containing β-lactose crystals to the spray drying unit 2. Atomize it into fine droplets through the nozzle 2-1, and use the temperature controller 2-4 to adjust the temperature in the atomization chamber 2-2, so that α-lactose crystallizes and embeds on the surface of the β-lactose crystals, forming composite embedded structure α / β anhydrous lactose microparticles. The nozzle 2-1 has adjustable spray droplet size and speed. The diameter of the nozzle 2-1 is 3 mm to achieve a spray droplet diameter of 50 μm. The spray pressure is 3 MPa to effectively control the spray droplet size. The temperature of the atomization chamber 2-2 is 150 °C to optimize the forming and drying effects of the spray-dried microparticles of the α / β anhydrous lactose composite embedded structure.

[0064] 4. Transfer the spray-dried microparticles to the fluidized bed unit 3. Provide a constant temperature and air flow in the fluidized bed 3-1 with the heating system 3-2 and the fan 3-3, so that the microparticles are quickly dried and formed to obtain spherical α / β anhydrous lactose microparticles. The temperature of the heating system 3-2 is 150 °C to optimize the forming and drying effects of the spray-dried microparticles of the α / β anhydrous lactose composite embedded structure. The air flow rate is 3 m / s to maintain a constant air flow environment inside the system.

[0065] 5. Transfer the microparticles at the outlet of the fluidized bed to the collection unit 4. Separate and collect the microparticles with the filter 4-1 and the electrostatic precipitator 4-2, and remove the excess gas and impurities. Store the collected microparticles in the collector 4-3 or output them through the discharge port 4-4. The filtration efficiency of the filter 4-1 is 95% to achieve the efficient collection and separation of the spray-dried microparticles of the α / β anhydrous lactose composite embedded structure. The electrostatic field strength of the electrostatic precipitator 4-2 is 15 kV / m to achieve the efficient separation of the spray-dried microparticles.

[0066] See Figure 5 and Figure 6 , and the finally obtained anhydrous lactose microparticles have a particle size of 80 microns, a fast dissolution rate, a solubility of 30 g / 100 mL, and an average tablet hardness of 78 N.

[0067] During the whole preparation process, use the control unit 6 to monitor and adjust the working parameters of each unit in real time, such as temperature, pressure, flow rate, filtration efficiency, electrostatic field strength, etc., to ensure the quality and stability of the product.

[0068] Example 3

[0069] 1. Dissolve lactose in an appropriate amount of water to obtain a lactose solution. The concentration of the lactose solution is 30% to effectively control the formation of the spray-dried microparticles.

[0070] 2. Heat the lactose solution to 85°C, transfer it to the dissolution and recrystallization control unit 1, stir and filter it in the heating container 1-1. By utilizing the temperature change and the screening effect of the layered filter screen 1-2, high-purity β-lactose crystals are formed in the lactose solution, and their particle size and shape are controlled. The layered filter screen 1-2 has adjustable pore sizes and shapes to screen the required crystal nuclei. The temperature control device 1-4 of the dissolution and recrystallization program is a programmable logic controller, which can monitor, record, and adjust each temperature parameter in real time according to the established program to ensure that the content of crystal β-lactose in the precursor suspension fed into unit 2 during the production process is greater than 90%, so as to ensure the high uniformity and quality stability of the spray-dried particles of the α / β anhydrous lactose composite embedding structure.

[0071] 3. Transfer the lactose solution containing β-lactose crystals to the spray-drying unit 2, atomize it into fine droplets through the nozzle 2-1, and adjust the temperature in the atomization chamber 2-2 with the temperature controller 2-4 to make α-lactose crystallize and embed on the surface of the β-lactose crystals, forming composite-embedded structure α / β anhydrous lactose particles. The nozzle 2-1 has adjustable spray droplet sizes and speeds. The diameter of the nozzle 2-1 is 0.5 mm to achieve a spray droplet diameter of 5 μm. The spray pressure is 5 MPa to effectively control the spray droplet size. The temperature of the atomization chamber 2-2 is 200°C to optimize the forming and drying effects of the spray-dried particles of the α / β anhydrous lactose composite embedding structure.

[0072] 4. Transfer the spray-dried particles to the fluidized bed unit 3, and use the heating system 3-2 and the blower 3-3 in the fluidized bed 3-1 to provide a constant temperature and air flow to quickly dry and form the particles, obtaining spherical α / β anhydrous lactose particles. The temperature of the heating system 3-2 is 200°C to optimize the forming and drying effects of the spray-dried particles of the α / β anhydrous lactose composite embedding structure. The air flow rate is 5 m / s to maintain a constant air flow environment inside the system.

[0073] 5. Transfer the particles at the outlet of the fluidized bed to the collection unit 4, separate and collect the particles with the filter 4-1 and the electrostatic precipitator 4-2, and remove the excess gas and impurities. Store the collected particles in the collector 4-3 or output them through the discharge port 4-4. The filtration efficiency of the filter 4-1 is 99.9% to achieve the efficient collection and separation of the spray-dried particles of the α / β anhydrous lactose composite embedding structure. The electrostatic field intensity of the electrostatic precipitator 4-2 is 20 kV / m to achieve the efficient separation of the spray-dried particles.

[0074] See Figure 7 and Figure 8 , and the finally obtained anhydrous lactose particles have a particle size of 20 microns, an extremely fast dissolution rate, a solubility of 30 g / 100 mL, and an average hardness of 110 N.

[0075] During the whole preparation process, the control unit 6 is used to monitor and adjust the working parameters of each unit in real time, such as temperature, pressure, flow rate, filtration efficiency, electrostatic field strength, etc., to ensure the quality and stability of the product.

[0076] Figures 3 to 8 They are the electron microscope scanning images of the spray-dried lactose prepared with different parameters in Examples 1-3. The electron microscope scanning of the lactose particles prepared with different parameters shows that their particle sizes are uniformly controllable. The surface of β-lactose is coated with α-lactose to maintain the stability of the whole lactose composite particles, and at the same time, composite particles with uniform properties and adjustable ratios are obtained.

[0077] The above description is only the preferred embodiment of the present invention and is not intended to limit the present invention. It should be noted that for those of ordinary skill in the art, without departing from the technical principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing lactose particles using an apparatus for preparing composite-embedded α / β anhydrous lactose particles, characterized in that: The apparatus for preparing composite-embedded α / β anhydrous lactose particles includes a dissolution and recrystallization control unit and a control unit. The outlet end of the dissolution and recrystallization control unit is connected through a spray drying unit and a fluidized bed unit. The inlet end of the fluidized bed unit is connected to the collection unit. A circulating air duct is also provided on the collection unit. The control unit is electrically connected to the dissolution and recrystallization control unit, the spray drying unit, the fluidized bed unit, the collection unit, and the circulating air duct through electrical signals; The dissolution and recrystallization control unit includes a heating container, in which a layered filter screen and a programmed stirring device are provided. A dissolution and recrystallization program control system is also provided at the bottom of the heating container, which is used to realize the solubility curve of α-lactose / β-lactose with temperature change, and based on the solubility difference between α / β at different temperatures, the temperature change in the dissolution and recrystallization control unit 1 is adjusted by the temperature control system program, so as to release high-purity β-lactose crystals before spray drying, and the appropriate crystal grain size, particle size and shape are screened based on the layered screen; The layered filter screen has adjustable pore size and shape to screen the required crystal nuclei, and the dissolution / recrystallization program temperature control device is a programmable logic controller; The specific preparation steps are as follows: (1) Dissolve lactose in an appropriate amount of water to obtain a lactose solution; the concentration range of the lactose solution is 1% - 30% to effectively control the formation of spray-dried particles; (2) Heat the lactose solution to 80 - 85 °C, transfer it to the dissolution and recrystallization control unit, stir and filter in the heating container, and use the temperature change and the screening effect of the layered filter screen to form high-purity β-lactose crystals in the lactose solution, and control its particle size and shape; (3) Transfer the lactose solution containing β-lactose crystals to the spray drying unit, atomize it into fine droplets through a nozzle, and adjust the temperature in the atomization chamber with a temperature controller, so that α-lactose crystallizes and embeds on the surface of the β-lactose crystals to form composite-embedded α / β anhydrous lactose particles; (4) Transfer the spray-dried particles to the fluidized bed unit, and use the heating system and the fan in the fluidized bed to provide a constant temperature and air flow, so that the particles are quickly dried and formed to obtain spherical α / β anhydrous lactose particles; (5) Transfer the particles at the outlet of the fluidized bed to the collection unit, separate and collect the particles with a filter and an electrostatic precipitator, and remove excess gas and impurities. Store the collected particles in the collector or output them through the discharge port.

2. The method for preparing lactose particles using an apparatus for preparing composite-embedded α / β anhydrous lactose particles according to claim 1, characterized in that: The spray drying unit includes an atomization chamber. A temperature controller is installed in the inner cavity of the atomization chamber. A nozzle is also installed at the top of the atomization chamber. A pressure controller and a flow controller are provided on the nozzle. An atomizer is installed at the outlet end of the nozzle. The nozzle has adjustable spray droplet size and speed. The diameter range of the nozzle is from 0.5 mm to 5 mm, and the spray pressure range of the nozzle is from 0.5 MPa to 5 Mpa.

3. A method for preparing lactose particles using the equipment for preparing composite embedded structure α / β anhydrous lactose particles according to claim 1, characterized in that: The fluidized bed unit includes a fluidized bed. The bottom of the fluidized bed is connected through a heating system, a blower and an air inlet. An air outlet is also provided at the top of the fluidized bed. The heating system has adjustable temperature and flow rate. The temperature range of the heating system is from 40 °C to 200 °C, and the air flow velocity range of the air inlet is from 0.1 m / s to 5 m / s.

4. A method for preparing lactose particles using the equipment for preparing composite embedded structure α / β anhydrous lactose particles according to claim 1, characterized in that: The collection unit includes a filter. An electrostatic precipitator is connected to the rear end of the filter. The tail end of the electrostatic precipitator is communicated with a collector. An emission port is provided at the outlet of the collector. The filtration efficiency range of the filter is from 80% to 99.9%, and the electrostatic field intensity range of the electrostatic precipitator is from 2 kV / m to 20 kV / m. The filter and the electrostatic precipitator of the collection unit have adjustable filtration efficiency and electrostatic field intensity.

5. A method for preparing lactose particles using the equipment for preparing composite embedded structure α / β anhydrous lactose particles according to claim 1, characterized in that: The circulation air duct includes an air duct. An air valve and a wind speed controller are provided on the air duct.

6. A method for preparing lactose particles using the equipment for preparing composite embedded structure α / β anhydrous lactose particles according to claim 1, characterized in that: The control unit includes a programmable logic controller and a human-machine interface, and is used for real-time monitoring and adjustment of the working parameters of the spray drying unit, the fluidized bed unit, the collection unit and the circulation air duct.

7. A method for preparing lactose particles using the equipment for preparing composite embedded structure α / β anhydrous lactose particles according to claim 1, characterized in that: The programmable logic controller and the human-machine interface of the control unit can real-time monitor, record and adjust each working parameter.

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