阅读说明：本技术 一种蔗糖细颗粒及其制备方法、设备与应用 (Sucrose fine particles and preparation method, equipment and application thereof ) 是由 沈惠 母泽波 于 2019-04-04 设计创作，主要内容包括：本发明提供了一种蔗糖细颗粒,该蔗糖颗粒内部具有孔隙,外部近似球形,所述蔗糖细颗粒由纯蔗糖为原料制成,所述蔗糖细颗粒的粒径为20-120目,表观密度为0.4-0.6g/ml,休止角为30～38°。所述蔗糖细颗粒流动性好、溶解性好、可压性好,能够作为药用辅料,用于直接压片；所述制备方法通过控制流化床的体积与物料重量的比例、喷水泵的压力和热风量,能够制备上述可用于直接压片的蔗糖细颗粒。(The invention provides a sucrose fine particle, which is internally provided with pores and externally approximately spherical, wherein the sucrose fine particle is prepared by taking pure sucrose as a raw material, the particle size of the sucrose fine particle is 20-120 meshes, the apparent density is 0.4-0.6g/ml, and the angle of repose is 30-38 degrees. The sucrose fine particles have good fluidity, good solubility and good compressibility, and can be used as a pharmaceutical adjuvant for direct tabletting; the preparation method can prepare the sucrose fine particles for direct tabletting by controlling the ratio of the volume of the fluidized bed to the weight of the material, the pressure of the water spray pump and the hot air quantity.)

1. A sucrose fine particle characterized by: the fine sucrose particles are prepared from pure sucrose serving as a raw material, the particle size of the fine sucrose particles is 20-120 meshes, the apparent density is 0.4-0.6g/ml, and the angle of repose is 30-38 degrees.

2. The sucrose fine particle as set forth in claim 1, wherein: the particle size of the sucrose fine particles is 40-100 meshes, the apparent density is 0.4-0.6g/ml, and the angle of repose is 32-35 degrees.

3. The sucrose fine particle as set forth in claim 1, wherein: the particle size of the sucrose fine particles is 60-80 meshes, the apparent density is 0.43-0.53g/ml, and the angle of repose is 32 degrees.

4. The sucrose fine particle as set forth in claim 1, wherein: the sucrose particles have pores inside and approximately spherical outside.

5. The method for producing sucrose fine particles as described in any one of claims 1 to 4, comprising the steps of: the sugar powder is prepared by crushing sucrose, the obtained sugar powder is blown up by hot air flow in a fluidized bed, and water is sprayed simultaneously, wherein the ratio of the volume of the fluidized bed to the weight of the materials is not less than 10.75L/KG, the pressure of a water spray pump is 3-8 KG, and the hot air amount is 3000-8000 cubic meters/hour.

6. The method for producing sucrose fine particles as set forth in claim 5, characterized in that: the water spraying is carried out by a two-way compressed air spray gun, so that the controllable degree of the particle size of the prepared sucrose fine particles is higher.

7. Use of the sucrose fine particles as described in any one of claims 1 to 4 as a pharmaceutical excipient.

8. The use of claim 8, wherein: the sucrose fine particles serve as solid formulation excipients (fillers) and/or flavoring agents.

9. The boiling granulating dryer for preparing the sucrose fine granules as claimed in any one of claims 1 to 4, comprising an air inlet pipe (1), a fluidized bed (2) and an air outlet pipe (3) which are connected in sequence, wherein an air filter (11), a plate heat exchanger (12), an adjusting air valve (13), a hot air chamber (14) and a screen (15) are arranged in the air inlet pipe (1) in sequence, and a plurality of spray guns (21) are arranged in the fluidized bed (2) from bottom to top, characterized in that: the effective boiling volume of the fluidized bed (2) is 10.75L/KG, and the spray gun (21) is a two-way compressed air spray gun.

Technical Field

The invention belongs to the field of pharmaceutical excipients, and particularly relates to sucrose fine particles, and a preparation method, equipment and application thereof.

Background

Sucrose is an important auxiliary material in pharmaceutical preparations, can be used as a sweetening agent and a filling agent of solid preparation tablets, plays roles of flavoring, shaping and the like, is widely applied to the pharmaceutical preparations, and has the following application forms in China:

1. crystallization of sucrose: i.e., sucrose crystals, as a sweetener, flavoring agent, filler, binder, coating material for sugar-coated tablets in the formulation. The powder is used in tablets, generally can not be directly compressed, but needs to be crushed into powdery sucrose for use;

2. sucrose powder: the sucrose powder collected by USPNF20 is a mixture of sucrose (C12H22O11) and corn starch, and contains not less than 95% of sucrose. In the formulation, sucrose powder may be used when it is desired to rapidly dissolve the sugar therein for flavoring or sweetening. The product can also be used as diluent in solid preparation prescription, and can be used as binder and filler for wet granulation. However, sucrose powder has high viscosity and poor flowability, and cannot be used for direct tabletting of tablets. The particle size range is 14-150 mu m;

3. compressible sucrose: the compressible sucrose carried by USPNF20 contains 95.0% -98% of sucrose (C12H22O11), and also can contain starch, maltodextrin, invert sugar and proper glidant, and can be used for directly tabletting with the particle size range of 75-425 μm;

4. spherical sucrose particles: the sucrose spherical particles carried by USPNF20 have uniform granularity, contain 62.5-91.5% of sucrose and mainly comprise starch as other components; the PhEur-loaded sucrose spherical particles contain no more than 92% of sucrose, and the balance of corn starch, starch hydrolysate and pigment, are used as inert cores in capsules and tablets, particularly multi-particle sustained-release preparations, and are coated with medicaments firstly and then with polymer materials, wherein the particle size of the sucrose spherical particles is 200-2000 mu m. The product label has a nominal particle size range;

on one hand, common sucrose is crystal particles with large granularity, and the sucrose needs to be crushed into sucrose powder for use. The specific usage is as follows: pulverizing sucrose into sugar powder, mixing with other raw materials and adjuvants, making into soft mass, making into wet granule, drying, grading, and tabletting. Common cane sugar and pulverized sugar powder can not be directly tabletted in one step in tablet production, namely all raw and auxiliary materials are uniformly mixed once and then tabletted, and the reason is that: the sucrose has large particles, and although the flowability is good, the original particles exist in the tablet by direct compression, so that the appearance, dissolution, disintegration and other properties of the tablet are influenced; however, after sucrose is pulverized into powdered sugar, although the solubility is improved, the powdered sugar has poor fluidity and poor mixing, and the powdered sugar cannot be discharged smoothly in the production of tablets, so that uniform tablets cannot be pressed.

On the other hand, sucrose products currently available for direct compression, such as compressible sucrose, sucrose spheroids, contain at least 2% or more of non-sucrose components, such as starch, dextrin, etc., and cannot be used in the formulation of effervescent tablets, since these components cannot be dissolved in water, and the quality requirement of effervescent tablet formulations is that they dissolve in water as a clear liquid.

Therefore, the development of the sucrose granules which can be directly used for tabletting has great application prospect.

Disclosure of Invention

In view of the drawbacks of the prior art, it is an object of the present invention to provide a sucrose fine particle which has good flowability, good solubility, and good compressibility, and can be used for direct compression tableting.

It is another object of the present invention to provide a method for preparing sucrose fine particles.

It is a further object of the present invention to provide the use of the sucrose fine particles as a pharmaceutical excipient.

It is still another object of the present invention to provide an apparatus for preparing the above-mentioned fine sucrose particles.

In order to achieve the purpose, the invention provides the following technical scheme:

in a first aspect, the invention provides sucrose fine particles, wherein the sucrose fine particles are prepared from pure sucrose as a raw material, the particle size of the sucrose fine particles is 20-120 meshes, the apparent density is 0.4-0.6g/ml, and the angle of repose is 30-38 degrees.

Preferably, the sucrose fine particles have a particle size of 40 to 100 mesh, an apparent density of 0.4 to 0.6g/ml, and an angle of repose of 32 ° to 35 °.

Preferably, the sucrose fine particles have a particle size of 60 to 80 mesh, an apparent density of 0.43 to 0.53g/ml, and an angle of repose of about 32 °.

Preferably, the sucrose particles have pores inside and approximately spherical outside.

The inventor researches and discovers that the particle size, the apparent density and the angle of repose of the sucrose fine particles have great influence on the performance of the sucrose fine particles as the pharmaceutic adjuvant, and when the apparent density is more than 0.6g/ml, the sucrose fine particles are not beneficial to being uniformly mixed with other substances; the sucrose with the repose angle larger than 38 degrees has poor fluidity and poor mixing, and can not be discharged smoothly, while the sucrose fine particles provided by the invention have the apparent density of 0.4-0.6g/ml, the repose angle of 30-38 degrees, good fluidity and good compressibility, and can be used for direct tabletting.

In a second aspect, the present invention provides a method for preparing the above sucrose fine particles, comprising the steps of: the sugar powder is prepared by crushing sucrose, the obtained sugar powder is blown up by hot air flow in a fluidized bed, and water is sprayed simultaneously, wherein the ratio of the volume of the fluidized bed to the weight of the materials is not less than 10.75L/KG, the pressure of a water spray pump is 3-8 KG, and the hot air amount is 3000-8000 cubic meters/hour.

According to the preparation method, the water spraying is performed by a two-way compressed air spraying gun, so that the grain size of the prepared sucrose fine particles can be controlled to a higher degree; preferably, the water spraying is performed by a two-way compressed air spraying gun, and the fog drops sprayed by the two-way compressed air spraying gun are 0.5-20 microns.

The method blows the obtained powdered sugar by hot air flow, sprays water to lead the powdered sugar to be gathered into new particles again, the new particles collide in the hot air flow and are dried, the prepared sucrose fine particles have pores inside, smooth surface and good fluidity, can be used for direct tabletting in the production of tablets, and greatly saves the production cost of the tablets.

In a third aspect, the invention also provides the use of the above fine sucrose particles as a pharmaceutical excipient, in particular as an excipient (filler) and/or a flavoring agent for solid preparations. The sucrose fine particle raw material prepared by the invention is 100% of sucrose, does not contain other reducing sugar components, has good compatibility and use stability with medicines on one hand, and is beneficial to the stability of the prepared medicinal preparation; on the other hand, the tablet prepared by taking the auxiliary material as the auxiliary material can be completely dissolved in water to form a clear solution, and is particularly suitable for effervescent tablets.

According to the application of the invention, the solid preparation comprises but is not limited to tablets, granules, capsules and powder.

For use according to the present invention, the tablets include, but are not limited to, plain tablets, buccal tablets, sublingual tablets, buccal patches, chewable tablets, dispersible tablets, soluble tablets, effervescent tablets, vaginal effervescent tablets, sustained release tablets, controlled release tablets, enteric-coated tablets and orally disintegrating tablets; preferably, the tablets are plain tablets and effervescent tablets.

In a fourth aspect, the invention also provides a boiling granulation dryer for preparing the sucrose fine particles, which comprises an air inlet pipe, a fluidized bed and an air outlet pipe which are sequentially connected, wherein an air filter, a plate heat exchanger, an adjusting air valve, a hot air chamber and a screen separation net are sequentially arranged in the air inlet pipe, a plurality of spray guns are arranged in the fluidized bed from bottom to top, the effective boiling volume of the fluidized bed is not less than 10.75L/KG, and the spray guns are two-way compressed air spray guns.

Furthermore, the number of the spray guns is 5.

The sucrose fine particles provided by the invention have good fluidity, can be used for one-step tabletting in tablet production, and greatly saves the production cost; the sucrose content is extremely high, the effervescent tablet can be completely dissolved in water to form a clear solution after being produced into a tablet product, the effervescent tablet is particularly suitable for producing effervescent tablets, does not contain other reducing sugar components, is more stable in compatibility with medicines, and is more favorable for the medicine stability of the preparation product.

The invention provides a specific boiling granulation dryer, on one hand, the effective boiling volume during granulation is ensured by controlling the effective boiling volume of the fluidized bed to be not less than 10.75L/KG; on the other hand, a plurality of spray guns are arranged in the fluidized bed from top to bottom at different heights, and the hollow degree, the particle size, the apparent density and the like of the granulation can be adjusted by selecting the spray guns with different heights; in the third aspect, the spray gun of the dryer adopts two paths of compressed air, the atomization effect of the spray gun is obviously better than that of the spray gun with a single air path in the prior art, more uniform and finer atomized droplets of water can be obtained, the atomized droplets are the aggregation center of granulation, and pores are formed in the granules after the granulation and the drying are carried out, so that the water is evaporated. Therefore, the more uniform the atomization, the greater the range in which the particle size of the atomized droplets can be adjusted, and the greater the degree of control over the granulation of the product. The spray gun can spray 0.5-20 micron uniform fog drops by adjusting the pressure of compressed air. The boiling granulation dryer can produce sucrose fine particles with good fluidity, good solubility and good compressibility.

In particular, the present invention has the following outstanding advantages over the prior art:

(1) the sucrose content in the sucrose particles is up to 100%: the sugar fine particles are composed of 100% sucrose (C)₁₂H₂₂O₁₁) Forming;

currently, sucrose products that can be used for direct compression, such as compressible sucrose, sucrose spherical granules, all contain at least more than 2% of non-sucrose components; on one hand, the above sucrose product for direct compression cannot be used in the prescription of effervescent tablets, since these components cannot be dissolved in water, and the quality requirement of effervescent tablet formulation is that it is dissolved in water as a clear liquid; on the other hand, it is difficult to use as an oxidative pharmaceutical adjuvant due to the presence of higher levels of non-sucrose components, especially reducing sugars.

The sucrose particles of the invention can be completely dissolved in water to form clear solution after being produced into tablet products due to extremely high sucrose content, and are particularly suitable for producing effervescent tablets; meanwhile, the content of the sucrose component is extremely high, and the content of other components is extremely low, so that the compatibility of the sucrose particles and the medicament is more stable, and the stability of the medicament of a preparation product is more favorable.

(2) The sucrose particles have a particle size of 20-120 meshes, an apparent density of 0.4-0.6g/ml, and an angle of repose of below 38 deg.

The inventor finds that the particle size, apparent density and angle of repose of the sucrose fine particles have great influence on the performance of the sucrose fine particles as a pharmaceutic adjuvant; when the apparent density is more than 0.6g/ml, the mixture is not beneficial to being mixed with other substances; sucrose with an angle of repose greater than 38 degrees has poor fluidity and poor mixing, and cannot be discharged smoothly.

The sucrose particles have the particle size of 20-120 meshes, particularly the particle size of 60-80 meshes, the apparent density of 0.4-0.6g/ml, the angle of repose of 30-38 degrees, good fluidity, good disintegration and good compressibility, and can be used for direct tabletting.

The mesh number of the sucrose can be adjusted, so that the mesh number of the sucrose is relatively consistent with that of other materials in the preparation formula; the sucrose granules have pores inside, so that the sucrose granules have compressibility and become straight-pressing sucrose (direct-pressing sucrose); the sucrose particles are internally provided with pores, so that the apparent density of the sucrose particles is reduced, and the sucrose particles can be better mixed with other materials.

(3) The preparation process of the sucrose comprises the following steps: pulverizing commercially available sucrose to obtain sugar powder; blowing the obtained powdered sugar with hot air flow in fluidized bed, spraying water, and granulating in hot air flow to obtain white or quasi-white granules; the water spraying is carried out by a two-way compressed air spray gun, so that the controllable degree of the particle size of the prepared sucrose fine particles is higher.

The method blows the obtained powdered sugar by hot air flow, sprays water to lead the powdered sugar to be gathered into new particles again, the new particles collide in the hot air flow with the ratio of the fluidized bed volume to the material weight not less than 10.75L/KG, and the prepared sucrose fine particles have pores inside, smooth surfaces and good fluidity, can be used for direct tabletting in the production of tablets, and greatly saves the production cost of the tablets.

Drawings

Fig. 1 is a schematic structural diagram of a boiling granulation dryer.

Detailed Description

The sucrose fine particles of the present invention are further explained below.