CN114129521A - Calcium carbonate D3Granule and preparation method thereof - Google Patents
Calcium carbonate D3Granule and preparation method thereof Download PDFInfo
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Abstract
The invention relates to the technical field of medicines, and particularly relates to calcium carbonate D3Granule and its preparation method are provided. The invention dissolves the adhesiveAdding the solution to the surface of the mixed powder in a spray form, and performing fluidized bed granulation to obtain calcium carbonate substrate particles; the mixed powder comprises calcium carbonate, a diluent and a sweetener; adding the main drug solution to the surface of calcium carbonate substrate particles in a fluidized bed granulator in a spraying manner, coating, and then sequentially drying and granulating to obtain calcium carbonate D3Granules; the main drug solution comprises antioxidant and vitamin D3Powder and solvent. The preparation method provided by the invention adds the adhesive solution in a spraying mode in the granulation process on the fluidized bed, so that the qualified rate of the calcium carbonate substrate particles is high; by adding antioxidant and vitamin D3The main medicine solution of the powder is added to the surface of calcium carbonate substrate particles in a spraying mode, the qualification rate of the particles is high, and the vitamin D is3The content uniformity and stability are good.
Description
Technical Field
The invention relates to the technical field of medicines, and particularly relates to calcium carbonate D3Granule and its preparation method are provided.
Background
Calcium is a major element essential to human body and plays an important role in growth and development, health and disease, aging and death of human body. About 99.3% of calcium in human body exists in bones and teeth, and the rest 0.3-0.6% is distributed in soft tissues, extracellular fluid and blood, and plays an important physiological role in human body.
Calcium carbonate is the best calcium supplement raw material widely used, and has the advantages of high calcium content, low cost and good calcium supplement effect, calcium ions released by a human body after oral administration can participate in the formation of bones, the reconstruction of bone tissues after fracture, muscle contraction, nerve transmission, a blood coagulation mechanism, reduction of capillary permeability and the like. Vitamin D3The calcium-enriched health-care product is a fat-soluble vitamin, has the physiological functions of improving the absorption of a human body to calcium and phosphorus, enabling the levels of plasma calcium and plasma phosphorus to reach the saturation degree, promoting growth or skeleton calcification, promoting tooth health and the like, has the effect of promoting calcium absorption when being taken together with a calcium source, can effectively prevent and treat osteoporosis and fracture, and can increase bone density.
CN112220775A discloses a calcium carbonate and vitamin D-containing food3The preparation intermediate granule and the preparation method thereof comprise the following steps: a) adding water into calcium carbonate, adhesive and pharmaceutically acceptable adjuvants orWet granulating with 20-80% ethanol, drying until the water content is 0.5% -3%, and grading with a 30-60 mesh screen; b) screening to obtain the calcium carbonate particles of 40-100 meshes, c) performing fluidized bed bottom spraying/coating by taking the calcium carbonate particles as a substrate, wherein the method comprises the following steps: sequentially carrying out an isolation layer and vitamin D3Applying the medicinal materials to the medicinal layer, antioxidant protective layer and outermost protective layer, and drying to obtain calcium carbonate and vitamin D3The formulation intermediate granule of (1). However, the above preparation method prepares calcium carbonate and vitamin D by multiple bottom spray coating/drug application techniques3The intermediate particles are complex in process, and in the process of preparing the substrate by wet granulation, the calcium carbonate content is high, the material adhesion is poor, the wet granulation difficulty is high, and the particle shape is irregular; after drying, using a 30-60 mesh screen to complete granules, so that the yield of qualified calcium carbonate granules is further reduced; therefore, the calcium carbonate and vitamin D containing prepared by the preparation method3The granule qualification rate of the preparation intermediate granule is low, which is not beneficial to mass production.
Disclosure of Invention
In view of the above, the present invention provides a calcium carbonate D3Granules and preparation method thereof, calcium carbonate D prepared by the preparation method provided by the invention3The granule has high qualification rate, simple and easy operation, good reproducibility, and easy realization of large-scale production.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides calcium carbonate D3The preparation method of the granules comprises the following steps:
adding the adhesive solution to the surface of the mixed powder in a spray form, and performing fluidized bed granulation to obtain calcium carbonate substrate particles; the mixed powder comprises calcium carbonate, a diluent and a sweetener;
adding the main drug solution to the surface of calcium carbonate substrate particles in a fluidized bed granulator in a spraying manner, coating, and then sequentially drying and granulating to obtain calcium carbonate D3Granules; the main drug solution comprises antioxidant and vitamin D3Powder and solvent.
Preferably, the diluent comprises one or more of sorbitol, mannitol, xylitol and pregelatinized starch;
the sweetener comprises one or more of sucrose, glucose, sucralose, acesulfame potassium and steviosin;
the mass ratio of the calcium carbonate to the diluent to the sweetener is 500-1250: 95-145: 80-120 parts.
Preferably, the particle size of the mixed powder is 40-60 meshes.
Preferably, the binder in the binder solution comprises one or more of povidone, starch slurry and hydroxypropyl cellulose;
the concentration of the adhesive solution is 0.5-1.0 wt%;
the mass ratio of the calcium carbonate to the binder in the binder solution is 500-1250: 6 to 10.
Preferably, the operating parameters of the fluid bed granulation include: the frequency of a fan is 18-32 Hz, the air inlet temperature is 85-105 ℃, the temperature of the mixed powder is 55-65 ℃, the spraying rotating speed is 8-16 rpm, and the spraying pressure is 0.1-0.2 MPa.
Preferably, the antioxidant comprises sodium citrate and/or sodium ascorbate;
the calcium carbonate, the antioxidant and the vitamin D3The mass ratio of the powder is 500-1250: 8-12: 0.4 to 2;
the concentration of the antioxidant in the main medicine solution is 8-12 wt%, and the vitamin D3The powder concentration is 0.8-1.2 wt%.
Preferably, the working parameters of the coating include: the frequency of a fan is 16-24 Hz, the air inlet temperature is 80-100 ℃, the temperature of calcium carbonate substrate particles is 40-50 ℃, the spraying speed is 6-10 rpm, and the spraying pressure is 0.05-0.15 MPa.
Preferably, the granulating further comprises adding a flavoring agent to the granules obtained by granulating; the mass ratio of the calcium carbonate to the aromatic is 500-1250: 5 to 15.
The invention provides calcium carbonate D prepared by the preparation method in the technical scheme3Granules, comprising the following components: calcium carbonate and vitamin D3Powder, diluent, binder, sweetener and antioxidant.
Preferably, the composition comprises the following components in parts by mass: 500-1250 parts of calcium carbonate and vitamin D30.4-2 parts of powder, 95-145 parts of diluent, 80-120 parts of sweetener, 6-10 parts of adhesive and 8-12 parts of antioxidant.
The invention provides calcium carbonate D3The preparation method of the granules comprises the following steps: adding the adhesive solution to the surface of the mixed powder in a spray form, and performing fluidized bed granulation to obtain calcium carbonate substrate particles; the mixed powder comprises calcium carbonate, a diluent and a sweetener; adding the main drug solution to the surface of calcium carbonate substrate particles in a fluidized bed granulator in a spraying manner, coating, and then sequentially drying and granulating to obtain calcium carbonate D3Granules; the main drug solution comprises antioxidant and vitamin D3Powder and solvent. The invention carries out the granulation process on the fluidized bed, and the adhesive solution is added in a spraying form, thereby improving the adhesion degree of the mixed powder and having high grain qualification rate of the calcium carbonate substrate grains; in addition, the sweetening agent can also play the role of a binder to improve the adhesion degree of the components, so that the qualified rate of the granules is improved; by adding antioxidant and vitamin D3The main medicine solution of the powder is added to the surface of calcium carbonate substrate particles in a spraying mode, so that the calcium carbonate D is improved3Granule qualification rate of the granule and improved vitamin D3Poor content uniformity, and increased vitamin D content due to the addition of antioxidant3Stability at high temperature (60 ℃), light (5000Lx +/-500 Lx) and high humidity (75% relative humidity), calcium carbonate D3The granules are excellent in stability. In addition, the preparation method only needs one-time coating, has simple process, strong operability, controllable granularity and high production efficiency, improves the conditions that the wet granulation is easy to harden and difficult to granulate and the granularity does not meet the requirement in the traditional process, and is suitable for mass production.
The invention provides calcium carbonate D3Granules comprising calcium carbonate and vitamin D3Powder, diluent, binder, sweetener, antioxidant and solvent. The calcium carbonate D provided by the invention3The granule is prepared from calcium carbonate as main material and vitamin D3The powder is used as a medicine, and the adhesive degree among the components is improved by adding the adhesive, so that the calcium carbonate D is improved3The granule percent of pass of the granules; vitamin D is added by spraying3Powder and antioxidant for improving vitamin D3Content uniformity and improved vitamin D content3Stability at high temperature (60 ℃), light (5000Lx +/-500 Lx) and high humidity (75% relative humidity), calcium carbonate D3The stability of the granules is excellent; improved calcium carbonate D by adding diluent and sweetener3The granule has good taste, and can improve compliance of patients.
Detailed Description
The invention provides calcium carbonate D3The preparation method of the granules comprises the following steps:
adding the adhesive solution to the surface of the mixed powder in a spray form, and performing fluidized bed granulation to obtain calcium carbonate substrate particles; the mixed powder comprises calcium carbonate, a diluent and a sweetener;
adding the main drug solution to the surface of calcium carbonate substrate particles in a fluidized bed granulator in a spraying manner, coating, and then sequentially drying and granulating to obtain calcium carbonate D3Granules; the main drug solution comprises antioxidant and vitamin D3Powder and solvent.
In the present invention, all the raw material components are commercially available products well known to those skilled in the art unless otherwise specified.
The invention adds the adhesive solution to the surface of the mixed powder in a spraying mode, and carries out fluidized bed granulation to obtain the calcium carbonate substrate particles.
In the present invention, the mixed powder includes calcium carbonate, a diluent and a sweetener; the particle size of the mixed powder is preferably 40-60 meshes; the mixed powder is preferably obtained by mixing calcium carbonate, diluent and sweetener in a fluidized bed granulator. In the invention, the calcium carbonate is preferably sieved before use, and the sieving is not particularly limited in the invention, so that the particle size of the calcium carbonate can be 40-60 meshes. In the present invention, the diluent preferably includes one or more of sorbitol, mannitol, xylitol and pregelatinized starch, more preferably includes sorbitol, mannitol, xylitol or pregelatinized starch, and further preferably includes mannitol; the diluent is preferably sieved before use, and the sieving is not particularly limited in the invention, so that the particle size of the diluent can be 40-60 meshes. In the present invention, the sweetener preferably includes one or more of sucrose, glucose, sucralose, acesulfame potassium and steviosin, more preferably includes sucrose, glucose, sucralose, acesulfame potassium or steviosin, and further preferably sucrose; the sweetener is preferably sieved before use, and the sieving is not particularly limited in the invention, so that the particle size of the sweetener can be 40-60 meshes. In the invention, the mass ratio of the calcium carbonate, the diluent and the sweetener is preferably 500-1250: 95-145: 80 to 120, more preferably 700 to 1100: 100-130: 90 to 110, and more preferably 800 to 1000: 110-120: 100 to 110. In the invention, the particle size of the mixed powder is preferably 40-60 meshes; the calcium carbonate, the diluent and the sweetener are preferably sieved before use, and the mixed powder is preferably obtained by sieving after mixing the calcium carbonate, the diluent and the sweetener; the mixing method of the invention is not particularly limited, and the raw materials can be uniformly mixed.
In the present invention, the adhesive solution preferably includes an adhesive and a solvent, the adhesive preferably includes one or more of povidone, starch slurry and hydroxypropyl cellulose, more preferably includes povidone, starch slurry or hydroxypropyl cellulose, and further preferably includes povidone; the solvent preferably comprises one or more of water, ethanol and propylene glycol, more preferably comprises water, ethanol or propylene glycol, and further preferably water; (ii) a The water is preferably purified water; the concentration of the binder solution is preferably 0.5 to 1.0 wt%, more preferably 0.6 to 0.9 wt%, and further preferably 0.8 wt%; the solvent in the binder preferably comprises. In the invention, the mass ratio of the calcium carbonate to the binder in the binder solution is preferably 500-1250: 6-10, more preferably 700-1100: 7-9, and more preferably 800-1000: 8-9.
In the present invention, the operating parameters of the fluid bed granulation preferably include: the frequency of the fan is preferably 18-32 Hz, more preferably 20-30 Hz, and further preferably 25-28 Hz; the air inlet temperature is preferably 85-105 ℃, more preferably 90-100 ℃, and further preferably 95 ℃; the temperature of the mixed powder is preferably 55-65 ℃, more preferably 58-62 ℃, and further preferably 60 ℃; the rotating speed of the spraying is preferably 8-16 rpm, more preferably 10-14 rpm, and further preferably 12 rpm; the spraying pressure is preferably 0.1-0.2 MPa, more preferably 0.12-0.18 MPa, and even more preferably 0.15 MPa; the fluid bed granulation is preferably carried out in a fluid bed granulator, the granulation preferably being carried out under sealed conditions.
After the granulation, the present invention preferably further includes drying, and the present invention is not particularly limited to the drying, and the drying is performed until the moisture content is not more than 2.0%. In the present invention, the content of the calcium carbonate substrate particles having a particle size of 24 to 150 mesh in the calcium carbonate substrate particles is preferably not less than 85 wt%, more preferably 85 to 100 wt%, and further preferably 90 to 95 wt%.
After calcium carbonate substrate particles are obtained, the main drug solution is added to the surface of the calcium carbonate substrate particles in a fluidized bed granulator in a spraying mode for coating, and then the main drug solution is dried and granulated in sequence to obtain calcium carbonate D3And (4) granules.
In the invention, the main medicine solution comprises antioxidant and vitamin D3A powder and a solvent; the concentration of the antioxidant in the main medicine solution is preferably 8-12 wt%, more preferably 10 wt%, and vitamin D3The powder concentration is 0.8 to 1.2 wt%, more preferably 1.0 wt%. In the present invention, the antioxidant preferably comprises sodium citrate and/or sodium ascorbate, more preferably comprises sodium citrate or sodium ascorbate, and further preferably sodium citrate; the solvent preferably comprises one or more of water, ethanol and propylene glycol, more preferably comprises water, ethanol or propylene glycol, and further preferably water; the water is preferablyAnd (5) purifying the water. In the present invention, the main drug solution is preferably prepared by dissolving the antioxidant in the solvent and then adding the vitamin D3Mixing the powders. In the present invention, the calcium carbonate, the antioxidant and the vitamin D3The mass ratio of the powder is preferably 500-1250: 8-12: 0.4 to 2, more preferably 700 to 1100: 9-12: 0.5 to 1.8, preferably 800 to 1000: 10-11: 1 to 1.5.
In the present invention, the working parameters of the coating preferably include: the frequency of the fan is preferably 16-24 Hz, more preferably 18-22 Hz, and further preferably 20 Hz; the air inlet temperature is preferably 80-100 ℃, more preferably 85-95 ℃, and further preferably 90 ℃; the temperature of the calcium carbonate substrate particles is preferably 40-50 ℃, more preferably 42-48 ℃, and further preferably 50 ℃; the rotating speed of the spraying is preferably 6-10 rpm, more preferably 7-9 rpm, and further preferably 8 rpm; the spraying pressure is preferably 0.05-0.15 MPa, more preferably 0.08-0.12 MPa, and even more preferably 0.1 MPa; the coating is preferably carried out in a fluid bed granulator, the coating preferably being carried out under sealed conditions.
In the present invention, the drying conditions are not particularly limited, and the drying may be carried out until the moisture content is not more than 2.0%.
In the present invention, the size reduction is preferably performed by using a mesh, and the size of the mesh is preferably 24 to 30 mesh.
After the above-mentioned size stabilization, the present invention preferably further comprises adding an aromatic agent to the particles obtained by the above-mentioned size stabilization and mixing them to obtain calcium carbonate D3And (4) granules. In the present invention, the aromatic agent preferably includes one or more of sweet orange powder essence, honey essence, strawberry powder essence and orange essence, more preferably includes sweet orange powder essence, honey essence, strawberry powder essence or orange essence, and further preferably is sweet orange powder essence. In the invention, the mass ratio of the calcium carbonate to the aromatic is preferably 500-1250: 5 to 15, more preferably 700 to 1100: 7-12, and more preferably 800-1050: 10 to 12. In the present invention, the aromatic-adding mixing is preferably performed in a fluid bed granulator.
The invention provides the technical schemeCalcium carbonate D obtained by the preparation method3Granules comprising calcium carbonate and vitamin D3Powder, diluent, binder, sweetener and antioxidant.
The invention comprises the following components in parts by mass: 500-1250 parts of calcium carbonate and vitamin D30.4-2 parts of powder, 95-145 parts of diluent, 80-120 parts of sweetener, 6-10 parts of adhesive and 8-12 parts of antioxidant.
The calcium carbonate D provided by the invention is calculated by mass parts3The components of the granule comprise 500-1250 parts of calcium carbonate, preferably 700-1200 parts, more preferably 800-1100 parts, and further preferably 900-1000 parts.
Based on the mass portion of the calcium carbonate, the calcium carbonate D provided by the invention3The granule comprises vitamin D30.4 to 2 parts of powder, preferably 0.5 to 1.8 parts, more preferably 0.8 to 1.5 parts, and still more preferably 1 to 1.2 parts.
Based on the mass portion of the calcium carbonate, the calcium carbonate D provided by the invention3The granule comprises 95-145 parts of diluent, preferably 100-140 parts, more preferably 110-130 parts, and even more preferably 120-125 parts.
Based on the mass portion of the calcium carbonate, the calcium carbonate D provided by the invention3The granule comprises 80-120 parts of sweetener, preferably 85-115 parts, more preferably 90-110 parts, and further preferably 100-105 parts.
Based on the mass portion of the calcium carbonate, the calcium carbonate D provided by the invention3The granule comprises 6-10 parts of a binder, preferably 6.5-10.5 parts, more preferably 7-10 parts, and even more preferably 8-9 parts.
Based on the mass portion of the calcium carbonate, the calcium carbonate D provided by the invention3The components of the granules comprise 8-12 parts of antioxidant, preferably 8.5-11.5 parts, more preferably 9-11 parts, and further preferably 10-10.5 parts.
Based on the mass portion of the calcium carbonate, the calcium carbonate D provided by the invention3The components of the granules preferably also comprise 5-15 parts of aromatic, preferably 6-14 partsThe amount of the surfactant is preferably 7 to 12 parts, and more preferably 8 to 10 parts.
In the present invention, the types of the calcium carbonate, diluent, binder, sweetener, antioxidant and aromatic are preferably the same as those of the calcium carbonate D3The types of calcium carbonate, diluent, binder, sweetener, antioxidant and aromatic in the technical scheme of the preparation method of the granules are the same, and are not described again.
In the present invention, the calcium carbonate D3The granules preferably comprise the following components in parts by mass: 500-1250 parts of calcium carbonate, 0.4-2 parts of vitamin D3 powder, 95-145 parts of mannitol, 80-120 parts of cane sugar, 6-10 parts of povidone, 8-12 parts of sodium citrate and 5-15 parts of sweet orange powder essence, more preferably 700-1100 parts of calcium carbonate and vitamin D30.5-1.5 parts of powder, 100-130 parts of mannitol, 90-110 parts of cane sugar, 7-9 parts of povidone, 9-12 parts of sodium citrate and 7-12 parts of sweet orange powder essence, and further preferably 800-1000 parts of calcium carbonate and vitamin D31-1.5 parts of powder, 110-120 parts of mannitol, 100-110 parts of cane sugar, 8-9 parts of povidone, 10-11 parts of sodium citrate and 8-10 parts of sweet orange powder essence.
In the present invention, the calcium carbonate D3The granule is preferably used as calcium carbonate D for children3And (4) granules.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. 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
Calcium carbonate D for children3Granules (1000 bags) preparation raw materials: 750g of calcium carbonate, 141g of mannitol, 80g of sucrose, 8g of povidone, 10g of sodium citrate and vitamin D31g of powder, 10g of sweet orange powder essence and 992g of purified water.
Dissolving 8g of povidone in 992g of purified water, and stirring until the povidone is dissolved to obtain povidone aqueous solution with the concentration of 0.8 wt%;
sieving 750g of calcium carbonate, 141g of mannitol and 80g of sucrose by a 40-mesh sieve, adding into a fluidized bed granulator, starting sealing, setting the frequency of a fan to be 28Hz, the air inlet temperature to be 95 ℃, starting a spray liquid when the temperature of the materials is controlled to be 60 ℃, spraying povidone aqueous solution for granulation at the spray liquid rotating speed of 12rpm and the spray liquid pressure of 0.15MPa, and obtaining calcium carbonate substrate particles;
dissolving 10g sodium citrate in 90g purified water, stirring to dissolve, adding 1g vitamin D3Stirring and dispersing the powder uniformly to obtain a main drug solution; setting the frequency of a fan to be 20HZ, the air inlet temperature to be 90 ℃, starting a spray liquid when the material temperature is controlled to be 50 ℃, enabling the spray liquid to rotate at the speed of 8rpm and the spray liquid pressure to be 0.1MPa, spraying the main drug solution onto calcium carbonate substrate particles in a fluidized bed granulator, drying, grading by using a 24-30 mesh sieve, adding 10g of sweet orange powder essence, uniformly mixing, and preparing into 1000 bags (1 g per bag) to obtain the calcium carbonate D for the children3And (4) granules.
Examples 2 to 6
Pediatric calcium carbonate D was prepared according to the method of example 13Granules of calcium carbonate D of examples 2 to 63The raw materials for the preparation of granules are shown in table 1.
Comparative example 1
Pediatric calcium carbonate D was prepared according to the method of example 13Granules, calcium carbonate D of comparative example 13The raw materials for the preparation of granules are shown in table 1.
TABLE 1 calcium carbonate D of the children in examples 1 to 6 and comparative example 13Raw materials for preparing granule
Test example 1
Pediatric calcium carbonate D prepared in examples 1-33The results of the granule performance tests are shown in table 2:
TABLE 2 pediatric calcium carbonate D prepared in examples 1-33Results of granule Performance test
The particle size is determined by a particle size and particle size distribution determination method (0982 second method double-screening method) according to the general rules of the four parts of the 2020 edition of Chinese pharmacopoeia, the total mass percentage of particles which can not pass through a second sieve (24 meshes) and can pass through an eighth sieve (150 meshes) is determined, and the particle size is qualified when the particle size is not more than 15%.
As can be seen from Table 2, the medium and small calcium carbonates D prepared in examples 1 to 33The granule has high sucrose dosage, and has a sweet taste when the dosage of 1000 bags exceeds 120 g; when the amount of sucrose is 80g, the taste is slightly sweet, a small amount of powder is already in the granules, the particle size of the granules is about 13%, and the limit of 15% is already approached, which indicates that the amount of sucrose reaches the lower limit.
Test example 2
Pediatric calcium carbonate D prepared in examples 4 to 6 and comparative example 13Standing at 60 deg.C for 10 days, sampling at 0 day, 5 days and 10 days respectively to detect vitamin D3The results are shown in Table 3:
TABLE 3 pediatric calcium carbonate D prepared in examples 4-6 and comparative example 13High temperature of 60 deg.C vitamin D in granule form3Content (wt.)
As can be seen from Table 3, the addition of sodium citrate significantly increased vitamin D3The stability of the product is high, and the dosage of the sodium citrate is 12g/kg3Vitamin D in granules3Has no obvious change in stability.
Test example 3
Pediatric calcium carbonate D prepared in example 53Granule and commercial product of infantile calcium carbonate D3Particles (A)
) To carry out vitamin D3The content uniformity and stability were tested and the test results are shown in tables 4-5, wherein vitamin D is shown3Calculating the average value and RSD value of 10 samples according to the content uniformity; the method for testing influence factors comprises standing at high temperature (60 deg.C), illumination (5000Lx + -500 Lx) and humidity (relative humidity 75%) for 10 days, sampling at 0 day, 5 days and 10 days respectively to detect granule properties and vitamin D3And (4) content.
Test on the calcium carbonate D of 38 persons in the market3Particles (A)
) Pediatric calcium carbonate D prepared in examples 1-3 and 53Taste characterization of granules calcium carbonate D in infants3The taste of the granules was measured and the results are shown in Table 6.
Table 4 example 5 and commercial pediatric calcium carbonate D3Particles (A)
) Vitamin D3Content uniformity
Table 5 example 5 and commercial pediatric calcium carbonate D3Particles (A)
) Stability test results
TABLE 6 examples1-3 and example 5 and commercial pediatric calcium carbonate D3Particles (A)
) Taste contrast of
As can be seen from tables 4 to 6, it is combined with a commercially available product of pediatric calcium carbonate D3Particles (A)
) Compared with the prior art, the pediatric calcium carbonate D prepared by the invention3Vitamin D in granule3The content uniformity is better, the stability is better under the conditions of high temperature (60 ℃), illumination and humidity, and the mouthfeel is better.
Example 7
Calcium carbonate D3Granules (1000 bags) preparation raw materials: 750g of calcium carbonate, 123g of mannitol, 100g of sucrose, 6g of povidone, 10g of sodium citrate and vitamin D31g of powder, 10g of sweet orange powder essence and 744g of purified water.
Dissolving 6g of povidone in 744g of purified water, and stirring until the povidone is dissolved to obtain povidone aqueous solution with the concentration of 0.8 wt%;
sieving 750g of calcium carbonate, 123g of mannitol and 100g of cane sugar by a 40-mesh sieve, adding into a fluidized bed granulator, starting sealing, setting the frequency of a fan to be 28HZ, the air inlet temperature to be 95 ℃, starting a liquid spraying when the temperature of the materials is controlled to be 60 ℃, spraying povidone aqueous solution for granulation at the liquid spraying speed of 12rpm and the liquid spraying pressure of 0.15MPa, and obtaining calcium carbonate substrate particles;
dissolving 10g sodium citrate in 90g purified water, stirring to dissolve, adding 1g vitamin D3Stirring and dispersing the powder uniformly to obtain a main drug solution; setting the frequency of a fan to be 18HZ, the air inlet temperature to be 90 ℃, starting a spray liquid when the material temperature is controlled to be 50 ℃, spraying the main drug solution onto calcium carbonate substrate particles in a fluidized bed granulator at the spray liquid rotating speed of 8rpm and the spray liquid pressure of 0.1MPa, drying, grading by using a 24-30-mesh sieve, and adding 10g of sweetOrange powder essence is uniformly mixed in a fluidized bed granulator to prepare 1000 bags (1 g per bag) of the calcium carbonate D for children3And (4) granules.
Examples 8 to 10
Pediatric calcium carbonate D was prepared according to the method of example 73Granules of calcium carbonate D of examples 8 to 103The raw materials for granule preparation are shown in table 7.
Comparative examples 2 to 6
Pediatric calcium carbonate D was prepared according to the method of example 73Granules, calcium carbonate D of comparative examples 2 to 63The raw materials for granule preparation are shown in table 7.
TABLE 7 calcium carbonate D of the small particles in examples 7 to 10 and comparative examples 2 to 63Raw materials for preparing granule
Test example 4
Pediatric calcium carbonate D prepared in examples 7 to 10 and comparative examples 2 to 63The results of the granule test are shown in tables 8 to 9.
TABLE 8 pediatric calcium carbonate D prepared in examples 7-8 and comparative examples 2-43Results of granule Performance test
TABLE 9 pediatric calcium carbonate D prepared in examples 9-10 and comparative examples 5-63Results of granule Performance test
From tables 8-9, 1000 bags of pediatric calcium carbonate D3In the granule, calcium carbonate D for children is added when the consumption of polyvidone exceeds 10g3The granules of the granules become fluffy, and the granularity does not change obviously with the increase of the dosage of the povidone, which indicates that the povidone reaches the upper limit of the dosage; when the using amount of the sweet orange powder essence is less than 5g, the sweet orange powder essence is free of fragrance and does not play a role of an aromatic, but when the using amount exceeds 15g, the fragrance is too heavy, and the using amount is too large, so that the using amount of the sweet orange powder essence is moderate between 5 and 15 g.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. Calcium carbonate D3The preparation method of the granules is characterized by comprising the following steps:
adding the adhesive solution to the surface of the mixed powder in a spray form, and performing fluidized bed granulation to obtain calcium carbonate substrate particles; the mixed powder comprises calcium carbonate, a diluent and a sweetener;
adding the main drug solution to the surface of calcium carbonate substrate particles in a fluidized bed granulator in a spraying manner, coating, and then sequentially drying and granulating to obtain calcium carbonate D3Granules; the main drug solution comprises antioxidant and vitamin D3Powder and solvent.
2. The method of claim 1, wherein the diluent comprises one or more of sorbitol, mannitol, xylitol, and pregelatinized starch;
the sweetener comprises one or more of sucrose, glucose, sucralose, acesulfame potassium and steviosin;
the mass ratio of the calcium carbonate to the diluent to the sweetener is 500-1250: 95-145: 80-120 parts.
3. The method according to claim 1 or 2, wherein the mixed powder has a particle size of 40 to 60 mesh.
4. The method of claim 1, wherein the binder in the binder solution comprises one or more of povidone, starch slurry, and hydroxypropylcellulose;
the concentration of the adhesive solution is 0.5-1.0 wt%;
the mass ratio of the calcium carbonate to the binder in the binder solution is 500-1250: 6 to 10.
5. The process according to claim 1 or 4, characterized in that the operating parameters of the fluid bed granulation comprise: the frequency of a fan is 18-32 Hz, the air inlet temperature is 85-105 ℃, the temperature of the mixed powder is 55-65 ℃, the spraying rotating speed is 8-16 rpm, and the spraying pressure is 0.1-0.2 MPa.
6. The method of claim 1, wherein the antioxidant comprises sodium citrate and/or sodium ascorbate;
the calcium carbonate, the antioxidant and the vitamin D3The mass ratio of the powder is 500-1250: 8-12: 0.4 to 2;
the concentration of the antioxidant in the main medicine solution is 8-12 wt%, and the vitamin D3The powder concentration is 0.8-1.2 wt%.
7. The method of claim 1, wherein the coating operating parameters include: the frequency of a fan is 16-24 Hz, the air inlet temperature is 80-100 ℃, the temperature of calcium carbonate substrate particles is 40-50 ℃, the spraying speed is 6-10 rpm, and the spraying pressure is 0.05-0.15 MPa.
8. The production method according to claim 1, 2, 4, 6 or 7, characterized by further comprising adding a flavoring agent to the granulated particles after the granulation; the mass ratio of the calcium carbonate to the aromatic is 500-1250: 5 to 15.
9. Calcium carbonate D obtained by the production method according to any one of claims 1 to 83Granules, comprising the following components: calcium carbonate and vitamin D3Powder, diluent, binder, sweetener and antioxidant.
10. Calcium carbonate D according to claim 93The granule is characterized by comprising the following components in parts by mass: 500-1250 parts of calcium carbonate and vitamin D30.4-2 parts of powder, 95-145 parts of diluent, 80-120 parts of sweetener, 6-10 parts of adhesive and 8-12 parts of antioxidant.
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