Preparation process and equipment of traditional Chinese medicine multi-component sustained and controlled release pellet

Abstract

The invention discloses a preparation process and equipment of a traditional Chinese medicine multi-component sustained and controlled release pellet, the preparation process comprises the following steps: corresponding auxiliary materials are selected according to physicochemical properties of each component of traditional Chinese medicine raw materials and different structural requirements of the pellet, and the auxiliary materials comprise one or more of a flavoring agent, an excipient, a coloring agent, a filling agent and a cosolvent; the preparation equipment is used for preparing the traditional Chinese medicine multi-component sustained and controlled release pellet according to the preparation technology, traditional Chinese medicine liquid is subjected to double extraction, utilization of effective components of traditional Chinese medicine can be greatly improved, a composite pellet structure is adopted, and the technical problem of traditional Chinese medicine multi-component sustained and controlled release is solved through the double-mode design of quick release and quick release and quick release and slow release; according to the pellet core, the medicine can be quickly diffused through the inner quick-release coating, the outer side of the pellet core is also swelled when meeting water through the quick-release coating to be quickly diffused, the medicine can be slowly released through membrane erosion through the slow-release coating, and dual-mode release meets the requirements of different people.

Description

Technical Field

[0001] The present invention relates to the technical field of micropill preparation, and in particular to a preparation process and equipment for traditional Chinese medicine multi-component sustained-release micropills. Background Art

[0002] Due to the different physiques and absorption effects of children, adults, and the elderly, the physical and chemical properties of multi-component Chinese medicine raw materials vary greatly, making it difficult to release them synchronously. Existing multi-component Chinese medicine micropellets are not suitable for different user groups. Not only do they require the development of different production lines for different user groups, but they also cannot achieve precise controlled release of multi-component drugs at different release rates. Therefore, a preparation process and equipment for multi-component sustained-release micropellets of Chinese medicine are proposed. Summary of the Invention

[0003] The purpose of the present invention is to solve the problems mentioned in the above background technology, and provide a preparation process and equipment for traditional Chinese medicine multi-component sustained-release micropills.

[0004] In order to achieve the above-mentioned purpose, the present invention specifically adopts the following technical solutions:

[0005] A preparation process for traditional Chinese medicine multi-component sustained-release micropellets, comprising the following steps:

[0006] According to the physical and chemical properties of each component of the Chinese medicine raw materials and the different structural requirements of the micropills, the corresponding excipients are selected, and the excipients include one or more of flavoring agents, excipients, colorants, fillers, and cosolvents;

[0007] The raw materials of each component of traditional Chinese medicine are cleaned by a medicine washing machine to remove impurities and sediment on the surface, and the cleaned raw materials are put into a dryer at a temperature of 50-60°C to reduce the moisture content of the raw materials to 5%-8%;

[0008] The Chinese medicine raw materials and auxiliary materials are crushed separately, passed through a 60-80 mesh sieve, and the crushed Chinese medicine raw material components are added to the Chinese medicine extraction tank. Pure water 5 times the weight of the Chinese medicine raw material components is added, stirring is started and the temperature is raised to 75-90 ° C. Constant temperature extraction is carried out for 1-2 hours, and the filtrate is filtered to obtain the filtrate;

[0009] Weigh the mass of the filter residue, add 5 times the amount of pure water according to the mass of the filter residue, start stirring and heat to 85-90℃, extract at constant temperature for 2-3h, put the filter residue into the traditional Chinese medicine extraction tank, filter again, and combine the two filtrates;

[0010] The filtrate was placed in a vacuum concentrator and concentrated to 1 / 4 to 1 / 5 of the original volume at a temperature of 45-50°C and a pressure of -0.07 to -0.08 MPa;

[0011] Place the Chinese medicine concentrate and excipients in a mixer and mix at a speed of 10-15 r / min for 20-30 minutes;

[0012] The centrifugal granulator is used to prepare drug-containing pellet cores at a temperature of 45-50° C. The pellet cores have a particle size of 0.8-1.2 mm and a bulk density of 0.35-0.5 g / cm 3 .

[0013] Preferably, the method further comprises: preparing an inner layer quick-release coating material, dissolving the inner layer quick-release coating material in 8-10 times the amount of 80-95% ethanol by weight, stirring with a blender for 2-4 hours until completely dissolved, with a viscosity of 15-20 mPa·s, to obtain an inner layer quick-release coating solution.

[0014] Preferably, the inner layer quick-release coating material comprises 90-95% of a hypromellose aqueous dispersion, 2-9% of an anti-sticking agent (such as talc) and 1-2% of a lubricant, wherein the lubricant comprises one of hard sodium fumarate and magnesium stearate.

[0015] Preferably, the method further comprises: pouring the inner layer quick-release coating liquid into the liquid storage tank of a fluidized bed coating machine, spraying the inner layer quick-release coating onto the pellet cores by the fluidized bed coating machine, and then drying the pellet cores with hot air at a temperature of 40° C. for 4-6 hours in a dryer, so that the pellet cores gain 3%-5% in weight, thereby obtaining quick-release pellets.

[0016] Preferably, the process further comprises: preparing an outer layer quick-release coating material, dissolving the outer layer quick-release coating material in 8-10 times the amount of 80-95% ethanol by weight, stirring with a blender for 2-4 hours until completely dissolved, with a viscosity of 15-20 mPa·s, to obtain an outer layer quick-release coating solution.

[0017] Preferably, the outer sustained-release coating material comprises ethylcellulose aqueous dispersion, polyacrylic acid resin aqueous dispersion, plasticizer and anti-sticking agent.

[0018] Preferably, the method further comprises: preparing an outer layer sustained-release coating material, dissolving the outer layer sustained-release coating material in 8-10 times the amount of 80-95% ethanol by weight, stirring with a blender for 2-4 hours until completely dissolved, with a viscosity of 15-20 mPa·s, to obtain an outer layer quick-release coating solution.

[0019] Preferably, the outer quick-release coating material comprises a hypromellose aqueous dispersion, a plasticizer and an anti-sticking agent.

[0020] Preferably, the method further comprises: pouring the outer coating liquid into the liquid storage tank of a fluidized bed coating machine, spraying the outer coating liquid onto the pellet cores by the fluidized bed coating machine, and then drying the pellet cores with hot air at a temperature of 40° C. for 4-6 hours in a drying machine to increase the weight of the pellet cores by 8-12%, thereby obtaining sustained-release pellets.

[0021] A preparation device for traditional Chinese medicine multi-component sustained-release micropills, wherein the preparation device is used to prepare traditional Chinese medicine multi-component sustained-release micropills according to the above-mentioned preparation process.

[0022] The beneficial effects of the present invention are as follows:

[0023] The present invention performs double extraction on the traditional Chinese medicine liquid, which can greatly improve the utilization of the effective ingredients of traditional Chinese medicine, and adopts a composite micropill structure. Through the dual-mode design of quick release + quick release and quick release + sustained release, the technical problem of sustained and controlled release of multiple components of traditional Chinese medicine is solved. The pill core swells with water through the inner layer of quick-release coating to form pores, and the drug can diffuse rapidly. The outer side also swells with water through the quick-release coating to diffuse rapidly, and can be slowly released through membrane erosion through the sustained-release coating. The same production line can produce micropills with two different release rates. The effect is rapid in infants and long-lasting in adults. The dual-mode release is suitable for the needs of different groups of people, improves medication compliance, and is more conducive to large-scale production and the modern development of compound traditional Chinese medicine preparations. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below.

[0025] The present invention provides a preparation process of traditional Chinese medicine multi-component sustained-release micropills, comprising the following steps:

[0026] S1. Raw material classification: Based on the physical and chemical properties of each component of Chinese medicine raw materials, Chinese medicine raw materials are grouped and classified according to water solubility, incompatibility and volatility.

[0027] S2. Excipient Selection: Excipients are selected based on the different structures and requirements of the pellets. The excipients include one or more of flavoring agents, excipients, colorants, fillers, and cosolvents.

[0028] Among them, flavoring agents include sucrose, monosaccharide syrup, and sorbitol; excipients include dextrin and honey; colorants include carotene, turmeric, carmine, tartrazine, and caramel; fillers include starch, lactose, dextrin, sucrose, microcrystalline cellulose, inorganic salts (such as calcium hydrogen phosphate, calcium sulfate, calcium carbonate) and mannitol; solubilizers include benzoic acid, potassium iodide, and ethylenediamine.

[0029] S3. Raw material pretreatment: The raw materials of each component of the Chinese medicine are cleaned by a medicine washing machine to remove impurities and sediment on the surface of the Chinese medicine raw materials, and the cleaned raw materials are put into a dryer at a temperature of 50-60°C to reduce the moisture content of the raw materials to 5%-8%.

[0030] S4. Material crushing: Place the Chinese medicine raw materials and auxiliary materials in a crusher for crushing, and pass them through a 60-80 mesh sieve to ensure uniform particle size, which is conducive to the subsequent extraction and pill making process.

[0031] S5. Primary extraction: Add the crushed Chinese medicinal raw material components to the Chinese medicinal extraction tank, add 5 times the amount of pure water based on the weight of the Chinese medicinal raw material components, start stirring and raise the temperature to 75-90°C, extract at a constant temperature for 1-2 hours, and filter to obtain a filtrate.

[0032] S6. Secondary extraction: Weigh the mass of the filter residue, add 5 times the amount of pure water according to the mass of the filter residue, start stirring and raise the temperature to 85-90℃, extract at constant temperature for 2-3h, put the filter residue into the traditional Chinese medicine extraction tank, filter again, and combine the two filtrates.

[0033] S7. Vacuum concentration: Place the filtrate in a vacuum concentration tank and concentrate it to 1 / 4 to 1 / 5 of its original volume at a temperature of 45-50°C and a pressure of -0.07 to -0.08 MPa.

[0034] S8. Mixing: Place the Chinese medicine concentrate and excipients in a mixer and mix at a speed of 10-15 r / min for 20-30 minutes.

[0035] S9. Micropellet granulation: Using a centrifugal granulator at a temperature of 45-50°C, pellet cores containing the drug were prepared. The pellet size was 0.8-1.2 mm and the bulk density was 0.35-0.5 g / cm 3 .

[0036] S10. Prepare an inner layer rapid-release coating solution: dissolve the inner layer rapid-release coating material in 8-10 times the amount of 80-95% ethanol by weight, stir for 2-4 hours until completely dissolved, and obtain a viscosity of 15-20 mPa·s to obtain an inner layer rapid-release coating solution;

[0037] The inner layer quick-release coating material comprises 90-95% of a hydroxypropyl methylcellulose aqueous dispersion, 2-9% of an anti-adhesive agent (such as talc) and 1-2% of a lubricant, wherein the lubricant comprises one of hard sodium fumarate and magnesium stearate.

[0038] S11. Prepare inner-layer coated pellets: Pour the inner-layer rapid-release coating liquid into the liquid storage tank of a fluidized bed coater. Spray the inner-layer rapid-release coating onto the pellet cores using the fluidized bed coater. Dry the pellets in a dryer with hot air at 40°C for 4-6 hours until the pellet cores gain 3%-5% weight, thereby obtaining rapid-release pellets.

[0039] The setting parameters of the fluidized bed coating machine are as follows: air inlet temperature of 55-60°C, material temperature of 45-50°C, air outlet temperature of 35-40°C, atomization pressure of 0.1-0.2 MPa, and liquid supply rate of 5 mL / min;

[0040] S12. Prepare an outer coating solution: dissolve the outer sustained-release coating material or the outer immediate-release coating material in 8-10 times the amount of 80-95% ethanol by weight, stir for 2-4 hours until completely dissolved, and obtain an outer coating solution with a viscosity of 15-20 mPa·s;

[0041] Wherein, the outer coating material comprises one of an outer sustained-release coating material and an outer immediate-release coating material; the outer sustained-release coating material comprises an ethyl cellulose aqueous dispersion, a polyacrylic acid resin aqueous dispersion, a plasticizer and an anti-sticking agent; the outer immediate-release coating material comprises a hypromellose aqueous dispersion, a plasticizer and an anti-sticking agent;

[0042] Among them, the mass ratio of the ethyl cellulose aqueous dispersion and the polyacrylic acid resin aqueous dispersion is 1-2:10, accounting for 75% of the total amount of the outer coating material, the hypromellose aqueous dispersion accounts for 75% of the outer coating material, the plasticizer (such as polyethylene glycol, triethyl citrate) accounts for 15% of the outer coating material, and the anti-sticking agent (such as talc) accounts for 10% of the total amount of the outer coating material.

[0043] S13. Preparation of outer-coated pellets: The outer coating liquid was poured into the liquid reservoir of a fluidized bed coater, and the outer coating liquid was sprayed onto the pellet cores by the fluidized bed coater. The pellets were then dried in a dryer at 40°C for 4-6 hours, and the pellet cores gained 8-12% weight to obtain sustained-release pellets.

[0044] The setting parameters of the fluidized bed coating machine are as follows: air inlet temperature of 55-60°C, material temperature of 45-50°C, air outlet temperature of 35-40°C, atomization pressure of 0.1-0.2 MPa, and liquid supply rate of 5 mL / min;

[0045] S14. Drying: Dry the outer-coated sustained-release pellets in a fluidized bed dryer at an air inlet temperature of 40-50°C and a material temperature of 35-40°C for 2-3 hours to reduce the moisture content of the pellets to 2%-3%.

[0046] S15. Release testing: Using the paddle method, 900 mL of water was used as the dissolution medium. The temperature was set at (37 ± 0.5)°C and the rotation speed was 100 r / min. Samples were collected at different time points (e.g., 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, etc.). The cumulative release of the active ingredient in the pellets was determined by high-performance liquid chromatography (HPLC), and release curves were plotted.

[0047] The measured results showed that the rapid-release portion released ≥60% within 1 hour, and the sustained-release portion released ≤80% within 12 hours.

[0048] S16. Stability test: The prepared sustained-release micropellets were placed under accelerated test conditions (40°C, relative humidity 75%) for 6 months. Samples were taken regularly for testing and the content of the active ingredient was determined. The content difference was ≤±5%.

[0049] The present invention also provides a preparation device for traditional Chinese medicine multi-component sustained-release micropills, which includes a medicine washer, a grinder, a traditional Chinese medicine extraction tank, a filter, a vacuum concentration tank, a mixer, a centrifugal granulator, a stirrer, a fluidized bed coating machine, and a fluidized bed dryer. The preparation device is used to prepare traditional Chinese medicine multi-component sustained-release micropills according to the above-mentioned preparation process.

[0050] The above description of the disclosed embodiments is intended to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is intended to conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A preparation process for traditional Chinese medicine multi-component sustained-release micropellets, characterized in that: The following steps are involved: According to the physical and chemical properties of each component of the Chinese medicine raw materials and the different structural requirements of the micropills, the corresponding excipients are selected, and the excipients include one or more of flavoring agents, excipients, colorants, fillers, and cosolvents; The raw materials of each component of traditional Chinese medicine are cleaned by a medicine washing machine to remove impurities and sediment on the surface, and the cleaned raw materials are put into a dryer at a temperature of 50-60°C to reduce the moisture content of the raw materials to 5%-8%; The Chinese medicine raw materials and auxiliary materials are crushed separately, passed through a 60-80 mesh sieve, and the crushed Chinese medicine raw material components are added to the Chinese medicine extraction tank. Pure water 5 times the weight of the Chinese medicine raw material components is added, stirring is started and the temperature is raised to 75-90 ° C. Constant temperature extraction is carried out for 1-2 hours, and the filtrate is filtered to obtain the filtrate; Weigh the mass of the filter residue, add 5 times the amount of pure water according to the mass of the filter residue, start stirring and heat to 85-90℃, extract at constant temperature for 2-3h, put the filter residue into the traditional Chinese medicine extraction tank, filter again, and combine the two filtrates; The filtrate was placed in a vacuum concentrator and concentrated to 1 / 4 to 1 / 5 of the original volume at a temperature of 45-50°C and a pressure of -0.07 to -0.08 MPa; Place the Chinese medicine concentrate and excipients in a mixer and mix at a speed of 10-15 r / min for 20-30 minutes; The pellet cores containing the drug were prepared by centrifugal granulator at a temperature of 45-50°C. The pellet cores had a particle size of 0.8-1.2 mm and a bulk density of 0.35-0.5 g / cm 3 .

2. The preparation process of a traditional Chinese medicine multi-component sustained-release micropill according to claim 1, characterized in that: Also includes: Prepare the inner layer quick-release coating material, dissolve the inner layer quick-release coating material in 8-10 times the amount of 80-95% ethanol by weight, stir with a blender for 2-4 hours until completely dissolved, with a viscosity of 15-20 mPa·s, to obtain the inner layer quick-release coating solution.

3. The preparation process of a traditional Chinese medicine multi-component sustained-release micropill according to claim 2, characterized in that: The inner layer quick-release coating material comprises 90-95% of hypromellose aqueous dispersion, 2-9% of anti-sticking agent (such as talc) and 1-2% of lubricant, wherein the lubricant comprises one of hard sodium fumarate and magnesium stearate.

4. The preparation process of a traditional Chinese medicine multi-component sustained-release micropill according to claim 2, characterized in that: Also includes: The inner layer quick-release coating liquid is poured into the liquid storage tank of the fluidized bed coater. The inner layer quick-release coating is sprayed onto the pellet core by the fluidized bed coater. The pellet core is then dried in a dryer with hot air at 40°C for 4-6 hours. The pellet core weight increases by 3%-5% to obtain quick-release pellets.

5. The preparation process of a traditional Chinese medicine multi-component sustained-release micropill according to claim 2, characterized in that: Also includes: Prepare the outer layer quick-release coating material, dissolve the outer layer quick-release coating material in 8-10 times the amount of 80-95% ethanol according to the weight ratio, stir with a blender for 2-4 hours until completely dissolved, and the viscosity is 15-20mPa·s to obtain the outer layer quick-release coating liquid.

6. The preparation process of a traditional Chinese medicine multi-component sustained-release micropill according to claim 5, characterized in that: The outer sustained-release coating material comprises ethyl cellulose aqueous dispersion, polyacrylic acid resin aqueous dispersion, plasticizer and anti-sticking agent.

7. The preparation process of a traditional Chinese medicine multi-component sustained-release micropill according to claim 5, characterized in that: Also includes: Prepare the outer layer sustained-release coating material, dissolve the outer layer sustained-release coating material in 8-10 times the amount of 80-95% ethanol by weight, and stir with a blender for 2-4 hours until completely dissolved, with a viscosity of 15-20 mPa·s to obtain the outer layer quick-release coating solution.

8. The process for preparing a traditional Chinese medicine multi-component sustained-release micropill according to claim 7, characterized in that: The outer quick-release coating material comprises a hypromellose aqueous dispersion, a plasticizer and an anti-sticking agent.

9. The preparation process of a traditional Chinese medicine multi-component sustained-release micropill according to claim 5 or 7, characterized in that: Also includes: The outer coating liquid is poured into the liquid storage tank of the fluidized bed coating machine, and the outer coating liquid is sprayed onto the pellet core by the fluidized bed coating machine, and then dried in a dryer with hot air at a temperature of 40°C for 4-6 hours to increase the weight of the pellet core by 8-12% to obtain sustained-release micropellets.

10. A preparation device for multi-component sustained-release micropellets of traditional Chinese medicine, characterized by: The preparation equipment is used for preparing traditional Chinese medicine multi-component sustained-release micropills according to a preparation process of traditional Chinese medicine multi-component sustained-release micropills according to any one of claims 1 to 9.