CN110656206B

CN110656206B - Sucrose refining method capable of controlling granularity

Info

Publication number: CN110656206B
Application number: CN201910906021.2A
Authority: CN
Inventors: 唐波; 彭立辉
Original assignee: Hunan Xinlyufang Pharmaceutical Co ltd
Current assignee: Hunan Xinlyufang Pharmaceutical Co ltd
Priority date: 2019-09-24
Filing date: 2019-09-24
Publication date: 2022-11-08
Anticipated expiration: 2039-09-24
Also published as: CN110656206A

Abstract

The invention discloses a novel sucrose refining method capable of controlling granularity, which comprises the steps of dissolving and decoloring edible sucrose to obtain fine filtrate, concentrating and crystallizing the fine filtrate to obtain sucrose crystals, and purifying and drying the sucrose crystals to obtain medicinal sucrose grains. The crystallization method combining seed crystal crystallization and ultrasonic wave stimulation assisted crystallization is creatively adopted, the grain size of the medicinal sucrose crystal is effectively controlled by accurately controlling the parameters of seed crystal adding time, seed crystal adding amount, ultrasonic frequency, ultrasonic wave stimulation crystallization time, stirring speed and the like, the sucrose crystallization yield is improved, and the characteristics of small grain size, good fluidity and good solubility of the medicinal sucrose crystal are realized, so that the performance requirements of a direct-compression solid preparation on the medicinal sucrose auxiliary material are met.

Description

Sucrose refining method capable of controlling granularity

Technical Field

The invention relates to the technical field of sucrose refining, in particular to a novel sucrose refining method capable of controlling particle size.

Background

Sucrose has been used as a pharmaceutic adjuvant at home and abroad for hundreds of years, and has been used as food for a longer time. It can be used as excipient, correctant, coating agent, granulating agent, suspension, sweetener, filler, therapeutic agent, and tackifier. 85% syrup or aromatic syrup is used as correctant for oral liquid preparation, 50% -67% syrup is used as binder for wet granulation, sucrose powder can be used as dry binder, sucrose can be used as binder for dry tabletting, and can be used as filler and sweetener for chewable tablet and lozenge. Therefore, medicinal sucrose is widely used in the production of solid preparations, is used in large amounts as an important filler and taste-modifying agent, and when the tablet formulation contains a large amount of sugar, the hardness of the tablet can be increased but the disintegration degree becomes poor.

Medicinal grade sucrose belongs to adjuvant drugs, and sucrose cannot simultaneously have low bulk density, good fluidity, mixing property and excellent compressibility even being subjected to sufficient pulverization treatment due to its natural crystal structure. On one hand, common sucrose is in a natural crystallization mode, crystal particles are large in particle size, and although the flowability is good, the original particles exist in the tablet by direct tabletting, so that the appearance, dissolution, disintegration and other properties of the tablet are influenced; on the other hand, after sucrose is crushed into powdered sugar, although the solubility is improved, the crystal form of the product is damaged, the powdered sugar is easy to agglomerate, the flowability of the powdered sugar is poor, the uniform mixing is poor, the feeding cannot be smooth in the production of tablets, and the uniform tablets cannot be pressed. Therefore, even if the existing medicinal sucrose is widely applied, the existing medicinal sucrose can only be applied to the conventional non-direct-compression solid preparation production process in a sucrose tablet, cannot be applied to the direct-compression solid preparation process, and cannot ensure that the tablet has good dissolution and disintegration properties. Therefore, there is a need to prepare a pharmaceutical sucrose adjuvant with low bulk density, good flowability, mixing and compression properties.

Disclosure of Invention

The invention aims to solve the technical problems that the crystal form of sucrose powder prepared by the prior art is damaged and easy to agglomerate, the flowability of the powder is poor, and the uniform mixing is poor, and provides a novel sucrose refining method which has mild purification process conditions, is simple and feasible, has lower cost, and is environment-friendly and capable of controlling the granularity.

The purpose of the invention is realized by the following technical scheme:

a novel sucrose refining method with controllable particle size comprises the following steps:

s1, dissolving and decoloring: dissolving edible sucrose in deionized water, adding decolorizing agent, stirring at constant temperature, and filtering to remove solid impurities to obtain fine filtrate.

S2, concentrating and crystallizing: and (3) stirring the fine filtrate obtained in the step (S1), concentrating until the sugar brix is 87 to 92 degrees Bx, adding a certain amount of sucrose seed crystals, stirring and dispersing, and simultaneously starting ultrasonic wave to stimulate and crystallize to obtain a crystalline liquid.

S3, separation and purification: and (3) separating the crystal liquid obtained in the step (S2) into coarse crystal grains and mother liquid, adding purified water into the coarse crystal grains, stirring, and performing centrifugal separation to obtain crystal washing grains and crystal washing liquid.

S4, drying and screening: and (4) drying and screening the crystal washing crystal grains obtained in the step (S3) to obtain medicinal-grade sucrose crystal grains.

Further, the edible sucrose dissolved in the deionized water in the S1 is stirred at a constant temperature of 75-85 ℃, and the mass ratio of the edible sucrose to the deionized water is 2-3: 1.

further, the addition amount of the decoloring agent in S1 is 0.05-0.1% of the quality of edible sucrose, and the decoloring agent adsorbs and removes pigments contained in edible sucrose. Preferably, the decolorizing agent S1 is injection-grade medicinal activated carbon, and can adsorb and remove micro-particle impurities contained in food grade. Further preferably, the particle size of the injection-grade medicinal activated carbon is 200 meshes, the contact area is larger, and the decoloring effect is good.

And further concentrating the fine filter liquid in the S2 under reduced pressure, wherein the concentration temperature is 70 to 80 ℃, and the concentration pressure is-0.09 to-0.07 Mpa.

Solution crystallization is the process of transforming a substance from a liquid state to a crystalline state, which includes two stages, nucleation and crystal growth. The aim of seeking high crystal growth rate in an industrial crystallizer is to improve the production capacity of equipment, but the crystallization is rapid, the crystal nucleus quantity is difficult to control, the crystal nucleus production speed is not matched with the crystal nucleus growth speed, so that the size of the recrystallized crystals cannot be controlled, granular crystals with different sizes are easy to appear in the production process, the yield and the quality of finished products are influenced, and the requirement that sucrose powder is used as a solid preparation cannot be met by adopting a recrystallization mode for providing supersaturation to improve the growth rate of the crystals. Through scientific analysis and a large number of experiments, the method realizes the control of the grain size of the sucrose crystal by adopting ultrasonic waves and the stimulation crystallization added by the seed crystal and controlling the time for adding the seed crystal, the quality of the seed crystal, the frequency of the ultrasonic waves and the time for stimulating the crystallization by the ultrasonic waves.

Furthermore, experiments prove that the method has better crystal growth speed when the sugar brix of the sucrose concentrate is 87 to 92 DEG Bx and is added for the seed crystal at a better time, the prepared crystal grain has no overlarge or undersize grain diameter, the sucrose crystal yield can be improved, and the sucrose crystallization time is shortened. Meanwhile, the addition amount of the sucrose seed crystal in the S2 is 0.1 to 0.3 percent of the quality of edible sucrose, and the quantity of the seed crystal influences the generation of crystal nuclei and the quality and yield of the crystal grains. Preferably, when the brix of the sucrose concentrate is 90 ° Bx, the amount of seed crystal added is 0.2% of the food-grade sucrose mass, which enables the generation and speed of crystal nuclei to be optimized.

Furthermore, the frequency of the ultrasonic wave stimulation crystallization in S2 is 1500-1700 Hz, and the time of the ultrasonic wave stimulation crystallization is 10-30min. In the crystal growth process, ultrasonic waves are assisted, and additional sound waves generate cavitation bubbles. The cavitation bubbles expand and grow and collapse quickly, and when the bubbles collapse, a liquid flow moving quickly is generated, and the liquid flow generates great impact force. When the size of the crystal is several times larger than that of the bubble, the liquid flow is jetted to the liquid-solid interface to form concave etching on the surface of the crystal, even the crystal is crushed, the crushed crystal is partially dissolved, and most of the crushed crystal is used as new crystal seeds to grow into the crystal. The invention controls the grain diameter of the crystal by controlling the ultrasonic frequency and time, and simultaneously ensures the integrity of the crystal form of the crystal. Preferably, the frequency of ultrasonic wave-stimulated crystallization in S2 is 1620Hz, the time is 20min, and the ultrasonic wave-stimulated crystallization can shorten the nucleation time of sucrose crystals, effectively shorten the crystallization time, and improve the production efficiency. Meanwhile, the produced sucrose crystals have smaller and more uniform granularity.

Further, the stirring speed of S2 is 22 to 35r/min, and preferably, the stirring speed of S2 is 28r/min.

Further, the highest centrifugal speed is 1000-1200 r/min, concentrated solution on the surface of the crystal is washed, crystal grains are prevented from caking, and better flowability of powdered sugar is guaranteed.

Further, the drying temperature of the crystal grain washing of the S4 is 63 to 67 ℃, and the drying time is 60 to 150min. The grain diameter of the sucrose crystal grain prepared by the method is 20-80 meshes, the purity is 99.9-99.99%, the fluidity is good, the water content is below 1.0%, and the product yield is 60-67%.

Compared with the prior art, the beneficial effects are that:

the invention creatively adopts edible sucrose as a raw material to produce and prepare medicinal refined sucrose, scientifically designs purification steps, adopts dissolution decolorization, decompression concentration, seed crystal crystallization and ultrasonic stimulation crystallization, separates and dries, and can obtain the sucrose auxiliary material which accords with Chinese pharmacopoeia by crystallization at a high speed under the condition of not using other organic solvents.

In the process of refining sucrose, the invention realizes effective control of the particle size of sucrose crystals by accurately controlling the parameters of the seed crystal addition time, the seed crystal addition amount, the ultrasonic frequency, the ultrasonic wave stimulated crystallization time, the stirring speed and the like, and simultaneously improves the sucrose crystallization yield, so that the prepared medicinal sucrose crystals have the characteristics of small particle size, good fluidity and good solubility, thereby meeting the performance requirements of a direct-compression solid preparation on medicinal sucrose auxiliary materials.

The sucrose crystal prepared by the method has the grain size of 20-80 meshes (the optimal grain size range used by a solid preparation), the purity reaches 99 percent, and the yield is not lower than 60 percent by adopting a seed crystal crystallization and ultrasonic stimulation assisted crystallization mode. The invention has mild refining conditions, can greatly improve the production efficiency of products, reduce the production cost, save energy and reduce consumption, improve the particle size and the fluidity of the products and enlarge the application range of the products.

Drawings

FIG. 1 is a flow chart of the present invention;

FIG. 2 is a diagram of a production apparatus for refining sucrose with controllable particle size according to the present invention.

The device comprises a dissolving tank 1, a stirrer 2, a steam jacket 3, a filter screen 4, a titanium rod filter 5, a fine filter liquid tank 6, a concentration tank 7, a purified water inlet 8, a vacuum generator 9, an ultrasonic generator 10, a crystal seed dispenser 11, a centrifuge 12 and a fluidization vibrator 13.

Detailed Description

The following examples are further explained and illustrated, but the present invention is not limited in any way by the specific examples. Unless otherwise indicated, the methods and equipment used in the examples are conventional in the art and all materials used are conventional commercially available materials.

The required production equipment is provided by the following companies:

device name	Model number	Number of	Production plant
				Dissolving tank	5m ³	1	Zibo bin combined chemical and equipment Limited
Titanium rod filter	9 core 30 inches	1	Haining Hengtai filtration plant
				Fine filtering liquid tank	22m ³	1	Ningxiang county culture of industry and trade Limited
Concentrating and crystallizing tank	3m ³	1	ZiBobin combined chemical and equipment Limited
				Clean centrifugal machine	PSB800-100L	1	Zhang Jia City Chengjia machinery Co Ltd
Fluidized vibration bed dryer	ZGL-4.5×0.6	1	Changzhou new industry granulation drying equipment Co
				Vibrating screen	S4910-B	1	Xinxiangdongzi machine manufacturing Co., ltd

Example 1

This embodiment provides a production facility that cane sugar of novel controllable granularity is refined.

A novel sucrose refining production system with controllable granularity comprises a dissolving tank 1, a titanium rod filter 5, a fine filtration liquid tank 6, a concentration tank 7, a centrifuge 12 and a fluidization vibrator 13. The discharge port of the dissolving tank 1 is connected with the feed port of a titanium rod filter 5, the discharge port of the titanium rod filter 5 is connected with the feed port of a fine filtration liquid tank 6, the discharge port of the fine filtration liquid tank 6 is connected with the feed port of a concentration tank 7, the discharge port of the concentration tank 7 is connected with a centrifuge 12, and the centrifuge 12 is connected with the inlet of a fluidized vibration machine 13.

A feed inlet is formed in the upper portion of the dissolving tank 1, a stirrer 2 is arranged in the dissolving tank, and a steam jacket 3 is installed around the dissolving tank 1 and used for heating and dissolving edible sucrose. A layer of filter screen 4 is arranged at the discharge port of the dissolving tank 1 and is used for preliminary filtering of the sucrose dissolving solution.

A stirrer 7 is arranged in the fine filtering liquid tank 6, and a filter screen 4 is arranged at a discharge hole of the fine filtering liquid tank 6. The upper part of the concentration tank 7 is provided with a purified water inlet 8, a seed crystal dispenser 11 and a vacuum generator 9, the inside of the concentration tank is provided with a stirrer 2 and an ultrasonic generator 10, and the periphery of the outside of the concentration tank is provided with a steam jacket 3.

The titanium rod filter 5 is not more than 0.5 micron, the sieve plate of the fluidization vibration machine 13 is in a fish scale hole shape, the hole diameter is 20-80 meshes, and the problem of hole leakage caused by small product fineness is avoided.

Example 2

This example provides a novel sucrose refining method with controllable particle size, which comprises the following steps:

s1, dissolving and decoloring: dissolving 10kg edible sucrose in 4kg deionized water, adding 8g active carbon for decolorizing, stirring at constant temperature of 80 deg.C until sucrose is dissolved, and filtering to obtain sucrose fine filtrate.

S2, concentrating and crystallizing: stirring the fine sucrose filtrate obtained in the step S1 at 28r/min, reducing the pressure to-0.09 to-0.07 Mpa, concentrating at 70 to 80 ℃ until the sugar brix is 90 degrees Bx, adding 20g of seed crystal, simultaneously starting ultrasonic waves, and regulating the frequency to 1620Hz to stimulate crystallization for 25min to obtain a crystalline liquid.

S3, separation and purification: and (3) centrifugally separating the crystal liquid obtained in the step (S2) into coarse crystal grains and mother liquid at 1000-1200 r/min, adding purified water into the coarse crystal grains, stirring, and centrifugally separating to obtain crystal washing grains and crystal washing liquid.

S4, drying and screening: and (4) drying the crystal grain obtained in the step (S3) at 63-67 ℃ to obtain medicinal sucrose crystal grains.

Example 3

s1, dissolving and decoloring: dissolving 10kg of edible sucrose in 5kg of deionized water, adding 10g of activated carbon for decolorization, stirring at a constant temperature of 85 ℃ until the sucrose is dissolved, and filtering to obtain a sucrose fine filtrate.

S2, concentrating and crystallizing: stirring the fine sucrose filter liquid obtained in the step S1 at 35r/min, reducing the pressure to-0.09 to-0.07 Mpa, concentrating at 70 to 80 ℃ until the sugar brix is 87 DEG Bx, adding 30g of seed crystal, simultaneously starting ultrasonic waves, and regulating the frequency to 1700Hz to stimulate crystallization for 20min to obtain a crystalline liquid.

S3, separation and purification: and (3) centrifuging the crystal liquid obtained in the step (S2) at 1000-1200 r/min to separate coarse crystal grains and a mother liquid, adding purified water into the coarse crystal grains, stirring, and centrifuging to separate to obtain crystal washing grains and a crystal washing liquid.

S4, drying and screening: and (4) drying the crystal grain obtained in the step S3 at 63-67 ℃ to obtain a medicinal sucrose crystal grain. Example 4

s1, dissolving and decoloring: dissolving 10kg edible sucrose in 3.3kg deionized water, adding 5g active carbon for decolorization, stirring at 75 deg.C until sucrose is dissolved, and filtering to obtain sucrose fine filtrate.

S2, concentrating and crystallizing: stirring the fine sucrose filtrate obtained in the step S1 at 22r/min, reducing the pressure to-0.09 to-0.07 Mpa, concentrating at 70 to 80 ℃ until the sugar brix is 92 degrees Bx, adding 10g of seed crystal, simultaneously starting ultrasonic waves, and regulating the frequency to be 1500Hz to stimulate crystallization for 20min to obtain a crystalline liquid.

S4, drying and screening: and (4) drying the crystal grain obtained in the step S3 at 63-67 ℃ to obtain a medicinal sucrose crystal grain. Example 5

S2, concentrating and crystallizing: stirring the fine sucrose filter liquid obtained in the step S1 at 28r/min, reducing the pressure to-0.09 to-0.07 Mpa, concentrating at 70 to 80 ℃ until the sugar brix is 87 DEG Bx, adding 10g of seed crystal, simultaneously starting ultrasonic waves, regulating the frequency to 1700Hz, and stimulating and crystallizing for 20min to obtain a crystalline liquid.

S4, drying and screening: and (4) drying the crystal grain obtained in the step S3 at 63-67 ℃ to obtain a medicinal sucrose crystal grain.

Example 6

S2, concentrating and crystallizing: stirring the fine sucrose filtrate obtained in the step S1 at 28r/min, reducing the pressure to-0.09 to-0.07 Mpa, concentrating at 70 to 80 ℃ until the sugar brix is 92 degrees Bx, adding 30g of seed crystal, simultaneously starting ultrasonic waves, and regulating the frequency to be 1500Hz to stimulate crystallization for 30min to obtain a crystalline liquid.

Comparative example 1

The method for supersaturation, temperature reduction and recrystallization of the sucrose is adopted in the comparative example, namely, excessive sucrose is dissolved at 90 ℃, activated carbon is added for decolorization, then the mixture is filtered to obtain a sucrose saturated solution, the mixture is stirred at 35r/min and is decompressed to-0.09 to-0.07 Mpa, then the temperature is reduced to the normal temperature at the cooling rate of 10 ℃/h, and the sucrose crystal is obtained after filtration and drying.

Comparative example 2

This comparative example is the same process as example 2 except that it concentrates the sucrose fine filtrate to a brix of 80 Bx.

Comparative example 3

This comparative example is identical to example 2 in process steps, except that it does not employ ultrasonic stimulation for crystallization.

Comparative example 4

This comparative example is identical to example 2 in process step, except that no seeding is added.

Comparative example 5

This example prepared pharmaceutical sucrose according to the method described in patent No. CN201510608123.8, a process for the production of pharmaceutical sucrose.

Examples of the experiments

According to the quality standard of sucrose pharmaceutic adjuvants in the Chinese pharmacopoeia, the particle size distribution, the product yield, the finished product purity and the impurity types of the sucrose prepared in the examples and the comparative examples are detected and compared, the detection method refers to the Chinese pharmacopoeia, and the results are shown in the table 1:

TABLE 1

The performance of the pharmaceutical grade sucrose crystals prepared in example 2 was examined according to the fourth part of the 'chinese pharmacopoeia' 2015 edition, and the results are shown in table 2:

TABLE 2

In order to further verify the feasibility of the production process of the method, a pilot scale experiment is carried out on the novel sucrose refining method with controllable granularity, and the production process is as follows:

s1, dissolving and decoloring: dissolving 500kg edible sucrose in 200kg deionized water, adding 400g active carbon for decolorization, stirring at 80 deg.C until sucrose is dissolved, and filtering to obtain sucrose fine filtrate.

S2, concentrating and crystallizing: stirring the refined sucrose solution obtained in the step S1 at 28r/min, reducing the pressure to-0.09 to-0.07 Mpa, concentrating at 70 to 80 ℃ until the sugar brix is 90 degrees Bx, adding 1kg of seed crystal, simultaneously starting ultrasonic waves, and regulating the frequency to 1620Hz to stimulate crystallization for 25min to obtain a crystalline liquid.

S3, separation and purification: centrifugally separating the crystal liquid obtained in the step S2 into coarse crystal grains and mother liquid, adding purified water into the coarse crystal grains, stirring, and centrifugally separating to obtain crystal washing grains and crystal washing liquid;

3 pilot experiments are carried out according to the method, the medicinal sucrose crystals obtained from the pilot experiments are detected according to Chinese pharmacopoeia for particle size distribution, product yield, finished product purity and impurity types, and the results are shown in Table 3:

the results show that the crystal grain size is effectively controlled by combining the crystal seed crystallization and the ultrasonic wave stimulated crystallization, the sucrose crystallization yield is improved, and the characteristics of small sucrose crystal grain size, good fluidity and good solubility are realized. The grain size of the sucrose crystal prepared by the method is 20 to 80 meshes (the optimal grain size range used by solid preparations), the purity reaches 99 percent, the yield is not lower than 60 percent, the fluidity is good, the sucrose crystal conforms to the standard of sucrose auxiliary materials in Chinese pharmacopoeia, and the sucrose crystal is an ideal auxiliary material for a direct-compression solid preparation production method.

It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A method for refining sucrose with controlled particle size, comprising the steps of:

s1, dissolving and decoloring: dissolving edible sucrose in deionized water, adding decolorizing agent, stirring at constant temperature, and filtering to obtain fine filtrate;

s2, concentrating and crystallizing: stirring the fine filtrate obtained in the step S1, concentrating the fine filtrate to form sucrose viscous liquid with the sugar hammer degree of 87-92 degrees Bx, adding a certain amount of sucrose crystal seeds, stirring and dispersing, and simultaneously opening ultrasonic waves to stimulate the sucrose viscous liquid to crystallize to obtain a crystallization liquid;

the addition amount of the sucrose seed crystal is 0.1-0.3% of the mass of edible sucrose;

the frequency of the ultrasonic wave stimulation crystallization is 1500-1700 Hz, and the time of the ultrasonic wave stimulation crystallization is 20-30 min;

s3, separation and purification: separating the crystal liquid obtained in the step S2 to obtain coarse crystal grains, adding the coarse crystal grains into purified water, washing and stirring, and performing centrifugal separation to obtain crystal washing grains;

s4, drying and screening: and (4) drying and screening the crystal washing crystal grains obtained in the step (S3) to obtain medicinal sucrose crystal grains.

2. The method for refining sucrose with controllable particle size according to claim 1, wherein the temperature of dissolving food-grade sucrose in deionized water at constant temperature is 75-85 ℃, and the mass ratio of food-grade sucrose to deionized water is 2-3: 1.

3. the method for refining sucrose with controllable granularity according to claim 1, wherein the addition amount of the decoloring agent S1 is 0.05-0.1% of the quality of edible sucrose.

4. The method of claim 1, wherein the decolorizing agent of S1 is injection grade pharmaceutical grade activated carbon.

5. The method as claimed in claim 1, wherein the concentration of the fine filtration liquid in S2 is performed under reduced pressure at 70-80 deg.C under-0.09 MPa to-0.07 MPa.

6. The method of claim 1, wherein the stirring speed of S2 is 22 to 35r/min.

7. The method of claim 1, wherein the centrifugation top speed of S3 is 1000 to 1200r/min.

8. The method of claim 1, wherein the temperature at which the washed crystal grains of S4 are dried is 63-67 ℃.