CN112294766A - Preparation method of medicinal auxiliary material sucrose spherical particles - Google Patents
Preparation method of medicinal auxiliary material sucrose spherical particles Download PDFInfo
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- CN112294766A CN112294766A CN202011209190.XA CN202011209190A CN112294766A CN 112294766 A CN112294766 A CN 112294766A CN 202011209190 A CN202011209190 A CN 202011209190A CN 112294766 A CN112294766 A CN 112294766A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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Abstract
The invention relates to the field of pharmaceutic adjuvants for sustained and controlled release pellet preparations, and particularly discloses a preparation method of pharmaceutic adjuvant sucrose spherical particles, which comprises the following steps: stirring and mixing 65-90% of sucrose and 10-35% of pregelatinized starch uniformly; putting the mixture into a centrifugal granulator, and carrying out operation for 3-5 minutes to complete granulation; putting the obtained particles into a multifunctional fluidized bed machine, and sieving the particles with a sieve of 25-30 meshes to obtain finished sucrose spherical particles; the method overcomes the defects of hardness, surface smoothness and roundness of the domestic medicinal sucrose pill core at present and the defect of large hygroscopicity caused by adopting syrup or sucrose aqueous solution as an adhesive, adopts sucrose and pregelatinized starch as raw materials, has simple preparation process, and can completely meet the requirements of sustained-release preparations and direct powder tabletting technology for the roundness, the surface smoothness and the friability of the pill core.
Description
Technical Field
The invention relates to the field of pharmaceutic adjuvants for sustained and controlled release pellet preparations, in particular to a preparation method of pharmaceutic adjuvant sucrose spherical particles.
Background
Sucrose spherical particles are used as inert cores in capsules and tablets, especially multiparticulate sustained release formulations, by first coating the drug on the core and then coating it with a polymeric material. Alternatively, the drug may be coated onto the core simultaneously with the polymeric matrix material, and the active drug may be released by erosion of the coating layer by diffusion. Different components of the compound preparation can be coated with different drug coatings on different batches of sucrose spherical particles.
The sustained-release sucrose spherical particles are a multi-unit administration dosage form, and are uniformly distributed in the gastrointestinal tract due to small particle size, so that the local irritation can be reduced, the drug release consistency is improved, and the adverse reaction caused by the burst release of the drug is reduced; the dosage form has high processing flexibility and is suitable for subsequent compression into pellet tablets or encapsulation. With the research progress of instruments, equipment, pharmaceutic adjuvants and preparation processes, the sustained-release sucrose spherical particles are greatly developed in preparation and clinical application with unique advantages. The common preparation method of the sustained-release pellet is to take a medicinal blank pellet core as an inner core, prepare the medicament-containing pellet by a powder lamination method or a liquid phase lamination method, and achieve the sustained-release effect after coating. Therefore, the properties of the medicinal blank pellet core such as particle size distribution, roundness, fluidity, friability and the like have important influence on the preparation technology of the sustained and controlled release pellet and the quality of finished products.
At present, syrup or a sucrose aqueous solution is mostly adopted as a bonding agent in domestic pellets, the syrup or the sucrose aqueous solution is relatively troublesome to prepare, the viscosity is difficult to control, the pellets are rich in nutrition and easy to grow bacteria, microorganisms are difficult to control, and the prepared sucrose pellets have large hygroscopicity. And the other method is a preparation method of adding sucrose, starch and dextrin, and the technical process is complicated.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for preparing sucrose spherical particles as a pharmaceutical adjuvant against the defects of the prior art, which overcomes the defects of hardness, surface smoothness and roundness of domestic pharmaceutical sucrose pellet cores at present and the defect of large hygroscopicity of syrup or sucrose aqueous solution as a binder.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of a medicinal adjuvant sucrose spherical particle comprises the following steps:
1) stirring and mixing 65-90% of sucrose and 10-35% of pregelatinized starch uniformly;
2) putting the mixture obtained in the step 1 into a centrifugal granulator, adjusting the air inlet temperature to be 12-16 Hz, adjusting the air inlet temperature to be 55 ℃ and the rotating speed to be 40-45 r/min, starting the centrifugal granulator, adjusting the rotating speed of a liquid spraying peristaltic pump to be 20-30 r/min, spraying aqueous solution under the atomizing pressure of 0.6MPa, stopping liquid spraying after the materials in the centrifugal granulator are fully wetted, adjusting the rotating speed of the centrifugal granulator to be 90-110 r/min, and performing operation for 3-5 minutes to complete granulation;
3) and (3) putting the particles obtained in the step (2) into a multifunctional fluidized bed machine, setting the air inlet temperature to be 50 ℃, adjusting the air inlet temperature to be 65 ℃ when the temperature of the material is increased to 25 ℃, cooling when the temperature of the material reaches 45 ℃, controlling the moisture content of the material to be less than or equal to 2.2%, and sieving with a sieve of 25-30 meshes to obtain the finished product of the spherical sucrose particles.
Preferably, in step 1, the weight ratio of the sucrose to the pregelatinized starch is 1: 4.
preferably, in step 2, in order to make the surface smoothness and the roundness of the granules meet the requirements, the centrifuge continues to operate for 5min after the granulation is finished.
The invention has the beneficial effects that:
the invention has simple preparation process, basically natural raw materials, simple physical mixing of the sucrose and the pregelatinized starch, easy quality control, convenient use and no interference of chemical synthetic substances to the medicinal preparation, overcomes the defects of large hygroscopicity caused by adopting syrup or sucrose aqueous solution as a bonding agent in the existing preparation process and the complex process of adding dextrin and starch into the sucrose, and completely meets the requirements of sustained-release preparations and direct powder tabletting technology on pellet core roundness, surface smoothness and friability.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A preparation method of a medicinal adjuvant sucrose spherical particle comprises the following steps:
1) stirring and mixing 65% of sucrose and 35% of pregelatinized starch uniformly; the pregelatinized starch is modified starch, is white or white-like powder with proper thickness, and has no odor and special taste.
2) Putting the mixture obtained in the step 1 into a centrifugal granulator, adjusting the air inlet temperature to be 12-16 Hz, adjusting the air inlet temperature to be 55 ℃ and the rotating speed to be 40-45 r/min, starting the centrifugal granulator, adjusting the rotating speed of a liquid spraying peristaltic pump to be 20-30 r/min, spraying aqueous solution under the atomizing pressure of 0.6MPa, stopping liquid spraying after the materials in the centrifugal granulator are fully wetted, adjusting the rotating speed of the centrifugal granulator to be 90-110 r/min, and performing operation for 3-5 minutes to complete granulation; in order to ensure that the surface smoothness and the roundness of the particles meet the requirements, the centrifuge continues to operate for 5min after the granulation is finished.
3) And (3) putting the particles obtained in the step (2) into a multifunctional fluidized bed machine, setting the air inlet temperature to be 50 ℃, adjusting the air inlet temperature to be 65 ℃ when the temperature of the material is increased to 25 ℃, cooling when the temperature of the material reaches 45 ℃, controlling the moisture content of the material to be less than or equal to 2.2%, and sieving with a sieve of 25-30 meshes to obtain the finished product of the spherical sucrose particles.
The general properties of the sucrose spherical granules obtained by the method are as follows:
specific surface area: 0.1 to 0.2m2Per gram, the particle size is less than 500 mu m; density: 1.50 to 1.57g/m3Fluidity: free flow < 10s, solubility: the solubility in water depends on the ratio of sucrose to pregelatinized starch. The sucrose component is readily soluble in water, while the pregelatinized starch component is insoluble in cold water.
The results of the test according to CP2015 pharmacopoeia are as follows:
| inspection item | Standard of spherical particles of sucrose | Test results |
| Chemical identification | Should be positive or negative | In a positive reaction |
| Heavy metals | ≤5ppm | Compliance with regulations |
| Loss on drying | ≤4.0％ | 2.6％ |
| Limit of microorganism | Should comply with the regulations | Compliance with regulations |
| Organic volatile impurities | Should comply with the regulations | Compliance with regulations |
| Particle size | Should comply with the regulations | Compliance with regulations |
| Residue on ignition | Not more than 0.2% | 0.1％ |
| Specific rotation degree | +41°～+61° | +54° |
| Content (sucrose) | 62.5％～91.5％ | 65％ |
Example 2
A preparation method of a medicinal adjuvant sucrose spherical particle comprises the following steps:
1) stirring and mixing 80% of sucrose and 20% of pregelatinized starch uniformly;
2) putting the mixture obtained in the step 1 into a centrifugal granulator, adjusting the air inlet temperature to be 12-16 Hz, adjusting the air inlet temperature to be 55 ℃ and the rotating speed to be 40-45 r/min, starting the centrifugal granulator, adjusting the rotating speed of a liquid spraying peristaltic pump to be 20-30 r/min, spraying aqueous solution under the atomizing pressure of 0.6MPa, stopping liquid spraying after the materials in the centrifugal granulator are fully wetted, adjusting the rotating speed of the centrifugal granulator to be 90-110 r/min, and performing operation for 3-5 minutes to complete granulation; in order to ensure that the surface smoothness and the roundness of the particles meet the requirements, the centrifuge continues to operate for 5min after the granulation is finished.
3) And (3) putting the particles obtained in the step (2) into a multifunctional fluidized bed machine, setting the air inlet temperature to be 50 ℃, adjusting the air inlet temperature to be 65 ℃ when the temperature of the material is increased to 25 ℃, cooling when the temperature of the material reaches 45 ℃, controlling the moisture content of the material to be less than or equal to 2.2%, and sieving with a sieve of 25-30 meshes to obtain the finished product of the spherical sucrose particles.
The general properties of the sucrose spherical granules obtained by the method are as follows:
specific surface area: 0.2m2(ii)/g, particle size 500 μm; density: 1.55g/m3Fluidity: free flow < 10s, solubility: the solubility in water depends on the ratio of sucrose to pregelatinized starch. The sucrose component is readily soluble in water, while the pregelatinized starch component is insoluble in cold water.
The results of the test according to CP2015 pharmacopoeia are as follows:
| inspection item | Standard of spherical particles of sucrose | Test results |
| Chemical identification | Should be positive or negative | In a positive reaction |
| Heavy metals | ≤5ppm | Compliance with regulations |
| Loss on drying | ≤4.0％ | 2.6％ |
| Limit of microorganism | Should comply with the regulations | Compliance with regulations |
| Organic volatile impurities | Should comply with the regulations | Compliance with regulations |
| Particle size | Should comply with the regulations | Compliance with regulations |
| Residue on ignition | Not more than 0.2% | 0.1％ |
| Specific rotation degree | +41°～+61° | +54° |
| Content (sucrose) | 62.5％～91.5％ | 80％ |
Example 3
A preparation method of a medicinal adjuvant sucrose spherical particle comprises the following steps:
1) stirring and mixing 90% of sucrose and 10% of pregelatinized starch uniformly;
2) putting the mixture obtained in the step 1 into a centrifugal granulator, adjusting the air inlet temperature to be 12-16 Hz, adjusting the air inlet temperature to be 55 ℃ and the rotating speed to be 40-45 r/min, starting the centrifugal granulator, adjusting the rotating speed of a liquid spraying peristaltic pump to be 20-30 r/min, spraying aqueous solution under the atomizing pressure of 0.6MPa, stopping liquid spraying after the materials in the centrifugal granulator are fully wetted, adjusting the rotating speed of the centrifugal granulator to be 90-110 r/min, and performing operation for 3-5 minutes to complete granulation; in order to ensure that the surface smoothness and the roundness of the particles meet the requirements, the centrifuge continues to operate for 5min after the granulation is finished.
3) And (3) putting the particles obtained in the step (2) into a multifunctional fluidized bed machine, setting the air inlet temperature to be 50 ℃, adjusting the air inlet temperature to be 65 ℃ when the temperature of the material is increased to 25 ℃, cooling when the temperature of the material reaches 45 ℃, controlling the moisture content of the material to be less than or equal to 2.2%, and sieving with a sieve of 25-30 meshes to obtain the finished product of the spherical sucrose particles.
The general properties of the sucrose spherical granules obtained by the method are as follows:
specific surface area: greater than 0.2m2(g), particle size greater than 500 μm, density: 1.55-1.58 g/m3Fluidity: free flow < 10s, solubility: the solubility in water depends on the ratio of sucrose to pregelatinized starch. The sucrose component is readily soluble in water, while the pregelatinized starch component is insoluble in cold water.
The results of the test according to CP2015 pharmacopoeia are as follows:
| inspection item | Standard of spherical particles of sucrose | Test results |
| Chemical identification | Should be positive or negative | In a positive reaction |
| Heavy metals | ≤5ppm | Compliance with regulations |
| Loss on drying | ≤4.0％ | 2.6％ |
| Limit of microorganism | Should conform toProvision for | Compliance with regulations |
| Organic volatile impurities | Should comply with the regulations | Compliance with regulations |
| Particle size | Should comply with the regulations | Compliance with regulations |
| Residue on ignition | Not more than 0.2% | 0.1％ |
| Specific rotation degree | +41°～+61° | +54° |
| Content (sucrose) | 62.5％～91.5％ | 90％ |
Finally, the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting, and other modifications or equivalent substitutions made by the technical solutions of the present invention by those of ordinary skill in the art should be covered within the scope of the claims of the present invention as long as they do not depart from the spirit and scope of the technical solutions of the present invention.
Claims (3)
1. A preparation method of a medicinal adjuvant sucrose spherical particle is characterized by comprising the following steps:
1) stirring and mixing 65-90% of sucrose and 10-35% of pregelatinized starch uniformly;
2) putting the mixture obtained in the step 1 into a centrifugal granulator, adjusting the air inlet temperature to be 12-16 Hz, adjusting the air inlet temperature to be 55 ℃ and the rotating speed to be 40-45 r/min, starting the centrifugal granulator, adjusting the rotating speed of a liquid spraying peristaltic pump to be 20-30 r/min, spraying aqueous solution under the atomizing pressure of 0.6MPa, stopping liquid spraying after the materials in the centrifugal granulator are fully wetted, adjusting the rotating speed of the centrifugal granulator to be 90-110 r/min, and performing operation for 3-5 minutes to complete granulation;
3) and (3) putting the particles obtained in the step (2) into a multifunctional fluidized bed machine, setting the air inlet temperature to be 50 ℃, adjusting the air inlet temperature to be 65 ℃ when the temperature of the material is increased to 25 ℃, cooling when the temperature of the material reaches 45 ℃, controlling the moisture content of the material to be less than or equal to 2.2%, and sieving with a sieve of 25-30 meshes to obtain the finished product of the spherical sucrose particles.
2. The method for preparing the sucrose spherical particles as the pharmaceutical adjuvant according to claim 1, is characterized in that: in step 2, in order to ensure that the surface smoothness and the roundness of the particles meet the requirements, the centrifuge continues to operate for 5min after the granulation is finished.
3. The method for preparing the sucrose spherical particles as the pharmaceutical adjuvant according to claim 1, is characterized in that: in step 1, the weight ratio of the sucrose to the pregelatinized starch is 1: 4.
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| CN202011209190.XA CN112294766A (en) | 2020-11-03 | 2020-11-03 | Preparation method of medicinal auxiliary material sucrose spherical particles |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113133973A (en) * | 2021-03-24 | 2021-07-20 | 江苏中邦制药有限公司 | Medicinal sucrose pill core and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6692768B1 (en) * | 1998-10-26 | 2004-02-17 | Tanabe Seiyaku Co., Ltd. | Preparation method of drug-containing spherical fine particles |
| JP2004359569A (en) * | 2003-06-03 | 2004-12-24 | Ogawa & Co Ltd | Sucrose fatty acid ester-containing granulated powder and method of preparing the powder |
| CN103920157A (en) * | 2014-04-23 | 2014-07-16 | 湖南尔康制药股份有限公司 | Medicinal modified starch type blank pellet |
| CN105148283A (en) * | 2015-09-28 | 2015-12-16 | 广东国源国药制药有限公司 | Innovative pharmaceutic adjuvant sucrose pill core and preparation method thereof |
-
2020
- 2020-11-03 CN CN202011209190.XA patent/CN112294766A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6692768B1 (en) * | 1998-10-26 | 2004-02-17 | Tanabe Seiyaku Co., Ltd. | Preparation method of drug-containing spherical fine particles |
| JP2004359569A (en) * | 2003-06-03 | 2004-12-24 | Ogawa & Co Ltd | Sucrose fatty acid ester-containing granulated powder and method of preparing the powder |
| CN103920157A (en) * | 2014-04-23 | 2014-07-16 | 湖南尔康制药股份有限公司 | Medicinal modified starch type blank pellet |
| CN105148283A (en) * | 2015-09-28 | 2015-12-16 | 广东国源国药制药有限公司 | Innovative pharmaceutic adjuvant sucrose pill core and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 门乐等: "4种辅料空白丸芯制备工艺的优选及差异性分析", 中国实验方剂学杂志, vol. 19, no. 10, pages 1 - 6 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113133973A (en) * | 2021-03-24 | 2021-07-20 | 江苏中邦制药有限公司 | Medicinal sucrose pill core and preparation method thereof |
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