CN115006363A - A kind of oyster calcium carbonate chewable tablet and preparation method thereof - Google Patents

Abstract

The invention belongs to the field of pharmaceutical preparations, and discloses oyster calcium carbonate chewable tablets and a preparation method thereof. According to the invention, the oyster calcium carbonate is protected by adopting the crosslinked povidone granulation coating to isolate citric acid, so that the reaction of the citric acid with calcium carbonate caused by easy moisture absorption is avoided, and the quality problem of the conventional oyster calcium carbonate chewable tablet caused by moisture absorption is effectively solved.

Description

A kind of oyster calcium carbonate chewable tablet and preparation method thereof

technical field

The invention relates to the field of pharmaceutical preparations, in particular to an oyster calcium carbonate chewable tablet and a preparation method thereof.

Background technique

Oyster calcium carbonate is the shell of marine organism oyster as raw material, which is prepared by high temperature calcination and electrolytic activation. The oyster shell contains more than 90% calcium carbonate, and its appearance is white powder, rich in calcium and manganese and zinc required by the human body. , silicon, phosphorus and other trace elements needed by the human body, oyster calcium carbonate is better than traditional calcium in solubility and absorption. Oyster calcium carbonate, also known as "active calcium", originated in Japan as a calcium supplement and is an excellent natural calcium source with biological activity and chemical activity. Today, oyster calcium carbonate is widely used in Europe and the United States, and has been included in the Chinese, American, British, and Japanese Pharmacopoeia, and is clinically used as a calcium supplement.

Oyster calcium carbonate chewable tablet, its pharmacological effect is that calcium in it participates in the formation of bones and the reconstruction of bone tissue after fracture, maintains nerve transmission and muscle contraction, reduces the permeability of capillaries, maintains its normal osmotic pressure, and also participates in coagulation mechanism, Maintain blood acid-base balance, etc. Indications are calcium supplementation for children, pregnant or lactating women, menopausal women and the elderly. At present, each oyster calcium carbonate chewable tablet contains 50 mg of oyster calcium carbonate in terms of calcium, and the excipients are citric acid, sucrose, starch, protein sugar, magnesium stearate, pigment (tartrazine), and hydroxypropyl cellulose.

But the existing oyster calcium carbonate chewable tablets generally adopt wet granulation, the citric acid in its prescription is easy to absorb moisture and cause a reaction with calcium carbonate, causing quality problems, citric acid is used as a flavoring agent and an acid agent for promoting calcium absorption , has a significant effect on the chewable tablet and cannot be easily replaced. Therefore, it is necessary to improve and innovate the existing production process of oyster calcium carbonate chewable tablets.

SUMMARY OF THE INVENTION

In order to solve the problem that citric acid easily absorbs moisture and causes a reaction with calcium carbonate in the existing oyster calcium carbonate chewing prescription, the invention provides an oyster calcium carbonate chewable tablet and a preparation method thereof.

To achieve the above object, the present invention adopts the following technical solutions:

The first aspect of the present invention is to provide a preparation method of an oyster calcium carbonate chewable tablet. The mixture of ketone and microcrystalline cellulose is granulated and coated, and the coated oyster calcium carbonate granules are mixed with citric acid granules containing citric acid and auxiliary materials, and then compressed into tablets.

Preferably, the preparation of described oyster calcium carbonate particles comprises the steps:

Taking the ethanolic solution of the hypromellose (HPMC) of recipe quantity as binder, the mixture of oyster calcium carbonate, crospovidone and microcrystalline cellulose is top-sprayed and granulated;

Taking the hypromellose (HPMC) of recipe quantity or its ethanol solution with food coloring as coating liquid, the top spray granules are carried out bottom spray coating to obtain oyster calcium carbonate granules.

More preferably, the oyster calcium carbonate is subjected to micronization treatment before granulation and coating, and passed through a 200-mesh sieve; and the coated oyster calcium carbonate particles are passed through a 16-mesh sieve.

Preferably, the concentration of the ethanol solution is 30-70%.

More preferably, the concentration of the ethanol solution is 40-65%.

More preferably, the concentration of the ethanol solution is 55-60%.

Preferably, the preparation of the citric acid granules comprises the following steps:

After mixing the citric acid of the recipe quantity with mannitol and sucrose, then adding the ethanol solution containing the auxiliary agent in the recipe quantity to carry out granulation, after drying, the citric acid granules are obtained;

Wherein, the auxiliary agent is selected from one or a combination of food essence, food coloring and sodium glutamate.

More preferably, the citric acid, mannitol and sucrose are pulverized and passed through an 80-mesh sieve before granulation; and the citric acid particles after granulation are passed through a 16-mesh sieve.

Preferably, the drying process is as follows: using hot air at 70-75° C., drying for 3-7 hours.

More preferably, the drying process is as follows: using hot air at 72-74° C., drying for 4-6 hours.

Preferably, the tableting process is:

The oyster calcium carbonate granules, citric acid granules and lubricants of the recipe quantity are evenly mixed and then pressed into tablets;

Wherein, the lubricant is selected from one or a combination of talc and magnesium stearate.

More preferably, the preparation method of described oyster calcium carbonate chewable tablet specifically comprises the steps:

(1) Preparation of oyster calcium carbonate particles

a. The oyster calcium carbonate is subjected to micronization treatment and passed through a 200-mesh sieve;

B, hypromellose (HPMC) is dissolved in ethanol solution, sieves 80 meshes, obtains adhesive, standby;

C, hypromellose (HPMC), food coloring are dissolved in ethanol solution, cross 80 mesh sieves, obtain isolation coating liquid, for subsequent use;

D, the oyster calcium carbonate, microcrystalline cellulose, crospovidone of the recipe quantity are mixed and placed in the granulation coating pot, sprayed into the adhesive, and carried out top spray granulation;

e. Pass the material obtained by top spraying through a 20-mesh screen to remove particles larger than 20-mesh;

f. The granules are placed in the granulation coating pot, sprayed into the isolation coating liquid, and the bottom is sprayed for coating;

g, the material after coating is crossed 16 mesh screen, rejects more than 16 mesh granules, obtains granule I;

(2) Preparation of Citric Acid Granules

A, the citric acid, mannitol and sucrose of the recipe quantity are pulverized through 80 mesh sieves;

b. Dissolve the edible essence, food coloring, and sodium glutamate of the prescription in the ethanol solution for subsequent use;

c. Put the treated citric acid, mannitol and sucrose into a high-speed granulator, stir at a slow speed for 1-3 minutes, add an ethanol solution containing an auxiliary agent, and quickly granulate for 2-5 minutes;

d. Spread the wet granules on a plate, send them to the drying room, and dry them with hot air at 70-75°C for 3-7 hours;

e. The material is passed through a 16-mesh screen, and the particles larger than 16-mesh are removed to obtain particle II;

(3) Tablet pressing

The granules I, the granules II, the talc and the magnesium stearate are mixed and pressed into tablets to obtain oyster calcium carbonate chewable tablets.

A second aspect of the present invention is to provide a chewable oyster calcium carbonate chewable tablet suitable for the above-mentioned preparation method, which comprises the following components in a prescription quantity (kg) per 10,000 tablets:

Preferably, the oyster calcium carbonate chewable tablet of the preparation method, in terms of the prescription quantity (kg) per 10,000 tablets, comprises the following components:

Preferably, the oyster calcium carbonate chewable tablet of the preparation method, in terms of the prescription quantity (kg) per 10,000 tablets, comprises the following components:

Preferably, the edible essence adopts one or more of sweet orange oil, lemon oil, and citrus oil; preferably, the edible essence adopts sweet orange oil.

Preferably, the food coloring adopts one or more of carmine, lemon yellow, and bright blue. The food coloring is not necessary for the plan, and the dosage is different according to different pigments. Blue uses 0.1g/10,000 pieces, tartrazine uses 0.7g/10,000 pieces, and then add granules I and granules II according to the material ratio.

The present invention adopts the above-mentioned technical scheme, compared with the prior art, has the following technical effects:

In the present invention, the ethanol solution of hypromellose (HPMC) is used as a binder to granulate the mixture of oyster calcium carbonate, crospovidone and microcrystalline cellulose, and then hypromellose (HPMC) is used for granulation. The ethanol solution of the oyster is used as a coating solution to coat the granules to obtain the oyster calcium carbonate granules; finally, the oyster calcium carbonate granules and the wet granulated citric acid granules are mixed and compressed into tablets. That is, hypromellose (HMPC) granulation coating is used to protect the oyster calcium carbonate, so as to isolate the citric acid and avoid the reaction with the calcium carbonate caused by the easy moisture absorption of the citric acid. Quality problems caused by moisture absorption.

And it is worth noting that the crospovidone (PVPP) in the present invention is used as a disintegrating agent, and the disintegrating agent is used here because the isolation layer coating will affect the dissolution rate, and adding a disintegrating agent can accelerate the main body. The drug is released in the oral cavity, and the adhesive and the barrier layer coating material of the present invention are both hypromellose (HPMC).

Detailed ways

The present invention will be described in detail and concretely below through specific embodiments, so as to make the present invention better understood, but the following embodiments do not limit the scope of the present invention.

Embodiment 1 The oyster calcium carbonate chewable tablet, according to the prescription amount (kg) per 10,000 tablets, includes the following components:

The preparation of oyster calcium carbonate chewable tablet includes the following steps:

(1) Preparation of oyster calcium carbonate particles

a. The oyster calcium carbonate is subjected to micronization treatment and passed through a 200-mesh sieve;

B, hypromellose (HPMC) is dissolved in ethanol solution, sieves 80 meshes, obtains adhesive, standby;

C, hypromellose (HPMC), food coloring are dissolved in ethanol solution, cross 80 mesh sieves, obtain isolation coating liquid, for subsequent use;

D, the oyster calcium carbonate, microcrystalline cellulose, crospovidone of the recipe quantity are mixed and placed in the granulation coating pot, sprayed into the adhesive, and carried out top spray granulation;

e. Pass the material obtained by top spraying through a 20-mesh screen to remove particles larger than 20-mesh;

f. The granules are placed in the granulation coating pot, sprayed into the isolation coating liquid, and the bottom is sprayed for coating;

g, the material after coating is crossed 16 mesh screen, rejects more than 16 mesh granules, obtains granule I;

(2) Preparation of Citric Acid Granules

A, the citric acid, mannitol and sucrose of the recipe quantity are pulverized through 80 mesh sieves;

b. Dissolve the edible essence, food coloring, and sodium glutamate of the prescription in the ethanol solution for subsequent use;

c. Put the treated citric acid, mannitol and sucrose into a high-speed granulator, stir at a slow speed for 2 minutes, add an ethanol solution containing an auxiliary agent, and quickly granulate for 3 minutes;

d. Spread the wet granules on a plate, send them to the drying room, and dry them with hot air at 70-75°C for 5 hours;

e. The material is passed through a 16-mesh screen, and the particles larger than 16-mesh are removed to obtain particle II;

(3) Tablet pressing

Mix Granule I, Granule II, talc and magnesium stearate and press into tablets to obtain oyster calcium carbonate chewable tablet 1.

Embodiment 2 Oyster calcium carbonate chewable tablet, by every ten thousand pieces of prescription quantity (kg), comprises the following components:

The preparation process of the oyster calcium carbonate chewable tablet is the same as that of Example 1.

Embodiment 3 Oyster calcium carbonate chewable tablet, by every ten thousand pieces of prescription quantity (kg), comprises the following components:

The preparation process of the oyster calcium carbonate chewable tablet is the same as that of Example 1.

Embodiment 4 The oyster calcium carbonate chewable tablet, according to the prescription quantity (kg) of every 10,000 tablets, comprises the following components:

The preparation process of the oyster calcium carbonate chewable tablet is the same as that of Example 1.

Embodiment 5 The oyster calcium carbonate chewable tablet, according to the prescription quantity (kg) of every 10,000 tablets, includes the following components:

The preparation process of the oyster calcium carbonate chewable tablet is the same as that of Example 1.

Comparative Example 1 Oyster calcium carbonate chewable tablet, calculated by the prescription amount (kg) per 10,000 tablets, includes the following components:

The preparation of oyster calcium carbonate chewable tablet includes the following steps:

(1) Preparation of oyster calcium carbonate particles

a. The oyster calcium carbonate is subjected to micronization treatment and passed through a 200-mesh sieve;

B, hypromellose (HPMC) is dissolved in ethanol solution, sieves 80 meshes, obtains adhesive, standby;

C, hypromellose (HPMC), food coloring are dissolved in ethanol solution, cross 80 mesh sieves, obtain isolation coating liquid, for subsequent use;

d, the oyster calcium carbonate and microcrystalline cellulose of the recipe quantity are mixed and placed in the granulation coating pot, sprayed into the adhesive, and carried out top spray granulation;

e. Pass the material obtained by top spraying through a 20-mesh screen to remove particles larger than 20-mesh;

f. The granules are placed in the granulation coating pot, sprayed into the isolation coating liquid, and the bottom is sprayed for coating;

g, the material after coating is crossed 16 mesh screen, rejects more than 16 mesh granules, obtains granule I;

(2) Preparation of Citric Acid Granules

A, the citric acid, mannitol and sucrose of the recipe quantity are pulverized through 80 mesh sieves;

b. Dissolve the edible essence, food coloring, and sodium glutamate of the prescription in the ethanol solution for subsequent use;

c. Put the treated citric acid, mannitol and sucrose into a high-speed granulator, stir at a slow speed for 2 minutes, add an ethanol solution containing an auxiliary agent, and quickly granulate for 3 minutes;

d. Spread the wet granules on a plate, send them to the drying room, and dry them with hot air at 70-75°C for 5 hours;

e. The material is passed through a 16-mesh screen, and the particles larger than 16-mesh are removed to obtain particle II;

(3) Tablet pressing

Mix Granule I, Granule II, talc and magnesium stearate and press into tablets to obtain oyster calcium carbonate chewable tablet 1.

Comparative Example 2 Oyster calcium carbonate chewable tablets, calculated by the prescription amount (kg) per 10,000 tablets, include the following components:

The preparation process of the oyster calcium carbonate chewable tablet is the same as that of Comparative Example 1.

Comparative Example 3 Existing oyster calcium carbonate chewable tablets, calculated by the prescription amount (kg) per 10,000 tablets, include the following components:

Prescription (10000 tablets)

According to the above-mentioned prescription, the existing oyster calcium carbonate chewable tablet adopts conventional wet granulation technology to prepare, and it mainly comprises the following steps: (1) mannitol, microcrystalline cellulose, sucrose, oyster calcium carbonate, citric acid The mixture is mixed with citric acid, sodium glutamate and pigment-dissolved water are used as wetting agents (if not enough to add ethanol), the mixture is granulated at a high speed, and magnesium stearate, talc, and essence are mixed externally, and then pressed into tablets.

Stability test:

Take the oyster calcium carbonate chewable tablet prepared from the embodiment 1 to the embodiment 5 of the novel process of the present invention as the experimental group, with the oyster calcium carbonate prepared by comparative example 1, comparative example 2 and comparative example 3 using the existing wet granulation process Chewable tablets were used as the control group, and accelerated stability experiments were carried out respectively. The specific experimental data are shown in Table 1 below.

Table 1 Summary of accelerated stability experimental data

It can be known from the accelerated stability experimental data of above-mentioned table 1 that adopt the oyster calcium carbonate chewable tablet prepared by the novel process of the present invention, after six months of accelerated investigation, the hardness and friability change are significantly improved compared with the original method, which can effectively avoid the Quality problems caused by tide.

The specific embodiments of the present invention have been described above in detail, but they are only used as examples, and the present invention is not limited to the specific embodiments described above. For those skilled in the art, any equivalent modifications and substitutions to the present invention are also within the scope of the present invention. Therefore, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be included within the scope of the present invention.

Claims (10)

1. a preparation method of oyster calcium carbonate chewable tablet, is characterized in that, with the ethanolic solution of hypromellose (HPMC) as adhesive to the mixture of oyster calcium carbonate, crospovidone and microcrystalline cellulose Carry out granulation and coating, and mix the coated oyster calcium carbonate granules with the citric acid granules containing citric acid and auxiliary materials, and then press into tablets. 2. the preparation method of oyster calcium carbonate chewable tablet according to claim 1, is characterized in that, the preparation of described oyster calcium carbonate particle, comprises the steps: Taking the ethanolic solution of the hypromellose (HPMC) of recipe quantity as binder, the mixture of oyster calcium carbonate, crospovidone and microcrystalline cellulose is top-sprayed and granulated; Taking the hypromellose (HPMC) of recipe quantity or its ethanol solution with food coloring as coating liquid, the top spray granules are carried out bottom spray coating to obtain oyster calcium carbonate granules. 3. the preparation method of oyster calcium carbonate chewable tablet according to claim 1 and 2, is characterized in that, described oyster calcium carbonate is processed through micronization before granulation coating, and crosses 200 mesh sieves; and after coating The described oyster calcium carbonate particles pass through a 16-mesh sieve. 4. The preparation method of the oyster calcium carbonate chewable tablet according to claim 1 or 2, wherein the concentration of the ethanol solution is 30-70%. 5. the preparation method of oyster calcium carbonate chewable tablet according to claim 1, is characterized in that, the preparation of described citric acid granule, comprises the steps: After mixing the citric acid of the recipe quantity with mannitol and sucrose, then adding the ethanol solution containing the auxiliary agent in the recipe quantity to carry out granulation, after drying, the citric acid granules are obtained; Wherein, the auxiliary agent is selected from one or a combination of food essence, food coloring and sodium glutamate. 6. the preparation method of oyster calcium carbonate chewable tablet according to claim 5, is characterized in that, described citric acid, mannitol and sucrose are processed through pulverization before granulation, and cross 80 mesh sieves; The citric acid particles were passed through a 16-mesh sieve. 7. The preparation method of oyster calcium carbonate chewable tablet according to claim 5, characterized in that, the drying process is as follows: using hot air at 70-75°C, drying for 3-7h. 8. the preparation method of oyster calcium carbonate chewable tablet according to claim 1, is characterized in that, described tabletting technique is: The oyster calcium carbonate granules, citric acid granules and lubricants of the recipe quantity are evenly mixed and then pressed into tablets; Wherein, the lubricant is selected from one or a combination of talc and magnesium stearate. 9. the preparation method of oyster calcium carbonate chewable tablet according to claim 1, is characterized in that, specifically comprises the steps: (1) Preparation of oyster calcium carbonate particles a. The oyster calcium carbonate is subjected to micronization treatment and passed through a 200-mesh sieve; B, hypromellose (HPMC) is dissolved in ethanol solution, sieves 80 meshes, obtains adhesive, standby; C, hypromellose (HPMC), food coloring are dissolved in ethanol solution, cross 80 mesh sieves, obtain isolation coating liquid, for subsequent use; d, the oyster calcium carbonate, microcrystalline cellulose, crospovidone of the recipe quantity are mixed and placed in the granulation coating pan, sprayed into the adhesive, and carried out top spray granulation; e. Pass the material obtained by top spraying through a 20-mesh screen to remove particles larger than 20-mesh; f. The granules are placed in the granulation coating pot, sprayed into the isolation coating liquid, and the bottom is sprayed for coating; g, the material after coating is crossed 16 mesh screen, rejects the particle greater than 16 mesh, obtains particle I; (2) Preparation of Citric Acid Granules A, the citric acid, mannitol, sucrose of the recipe quantity are pulverized through 80 mesh sieves; b. Dissolve the edible essence, food coloring, and sodium glutamate of the prescription in the ethanol solution for subsequent use; c. Put the treated citric acid, mannitol and sucrose into a high-speed granulator, stir at a slow speed for 1-3 minutes, add an ethanol solution containing an auxiliary agent, and quickly granulate for 2-5 minutes; d. Spread the wet granules on a plate, send them to the drying room, and dry them with hot air at 70-75°C for 3-7 hours; e. The material passes through a 16-mesh sieve, and the particles larger than 16-mesh are removed to obtain particle II; (3) Tablet pressing The granule I, the granule II, the talc and the magnesium stearate are mixed and pressed into tablets to obtain the oyster calcium carbonate chewable tablet. 10. a kind of oyster calcium carbonate chewable tablet for the preparation method described in any one of claim 1 to 9, is characterized in that, by every ten thousand pieces of prescription quantity (kg), comprises the following components: