Calcium carbonate and vitamin D3 composition and water-free swallowing granules thereof

Abstract

The invention relates to a calcium carbonate and vitamin D3 composition and water-free swallowing granules thereof. Belongs to the field of pharmaceutical preparations. In the calcium carbonate and vitamin D3 composition and the calcium carbonate and vitamin D3 water-free swallowing granules which comprise the composition or are prepared from the composition, vitamin D3 is fed in the form of a vitamin D3 carrier. Compared with the prior art, the granules can be swallowed quickly without water in the oral cavity, taste is good, compliance of a user is improved, the problems of poor content uniformity and poor stability of the vitamin D3 in a preparation are solved, and particularly, compared with an existing calcium carbonate vitamin D3 preparation, the content uniformity of the vitamin D3 in a unit preparation is greatly improved. The calcium carbonate content is increased, and meanwhile, the filling amount is smaller than that of a traditional dosage form.

Description

[0001] This application is a divisional application of a Chinese invention patent application with an application date of July 18, 2016, an application number of 2016105650024, and an invention title of "A Calcium Carbonate Vitamin D 3 Composition and Its anhydrous swallowable granules". Technical Field

[0002] The present invention provides a calcium carbonate vitamin D 3 Composition and its anhydrous swallowable granule. It belongs to the field of pharmaceutical preparations. Background Art

[0003] For calcium carbonate preparations, there are existing calcium carbonate tablets, calcium carbonate chewable tablets, and calcium carbonate granules. The conventional process is to add a disintegrant and a flavoring agent to the calcium carbonate granules and then fill them into stick packs or tablets. Taking calcium carbonate alone has poor absorption. Vitamin D 3 can assist calcium absorption. Therefore, the market for calcium carbonate vitamin D3 compound preparations is broader.

[0004] Vitamin D3 is insoluble in water and unstable, being sensitive to light and heat. To improve its solubility in oral compound preparations, β-cyclodextrin inclusion complexes are used to improve the solubility and stability of vitamin D3. Vitamin D3-β-cyclodextrin inclusion complexes are prepared and then made into solid preparations with other calcium-containing drugs to achieve the purpose of improving solubility and stability (Zhang Xuenong et al., Application of uniform experimental design in the prescription screening of compound calcium carbonate effervescent granules, Journal of Mathematical Medicine, 2000, 13(2):116)

[0005] CN00132317.2 discloses a calcium carbonate - xylitol solid dispersion and a compound calcium carbonate chewable tablet, where the compound calcium carbonate chewable tablet is made of a calcium carbonate - xylitol solid dispersion, zinc gluconate, vitamin D3 (vitamin D3-β-cyclodextrin), skimmed milk powder without sugar, starch, and talc powder.

[0006] CN201310192774.4 discloses a calcium-containing effervescent tablet and its preparation method and uses, where calcium carbonate and vitamin D (preferably vitamin D3) are mixed in equal mass proportions to obtain a mixture to ensure uniform content of vitamin D in each tablet.

[0007] CN201510743536.7 discloses a composition with calcium supplementing effect and its preparation, which includes 30 - 40 parts of milk mineral salts, 10 - 20 parts of acid milk powder, 10 - 15 parts of galactooligosaccharides, 3 - 5 parts of kudzu root powder, and 0.001 - 0.005 parts of vitamin D3.

[0008] Existing calcium carbonate vitamin D3 compound preparations have some defects. For example, vitamin D3 is prone to degradation, and the filling amount in the preparation is inaccurate. Summary of the Invention

[0009] To overcome the defects of the prior art, the present invention provides a calcium carbonate and vitamin D3 composition. The technical solution of the present invention is as follows:

[0010] The present invention provides a calcium carbonate and vitamin D3 composition, comprising calcium carbonate, vitamin D3 and a pharmaceutically acceptable excipient, characterized in that vitamin D3 is in the form of a vitamin D3 carrier and is made into the said composition together with calcium carbonate and a pharmaceutically acceptable excipient.

[0011] The above-mentioned vitamin D3 carrier is made of vitamin D3 and an excipient, and the excipient is selected from one or more of hydrogenated vegetable oil, gelatin, starch, sucrose, tocopherol; preferably, the vitamin D3 carrier is the vitamin D3 carrier of DSM.

[0012] In the above-mentioned composition, in a unit preparation, the dosage of calcium carbonate calculated as calcium can be 250 mg, 200 mg, 500 mg, preferably 500 mg; the dosage of the vitamin D3 carrier calculated as vitamin D3 can be 3 μg, 5 μg, preferably 5 μg.

[0013] As another object of the present invention, there is also provided a medicament comprising the above-mentioned composition, or a medicament made from the above-mentioned composition, such as oral solid preparations such as granules, tablets, capsules, etc.

[0014] Preferably, the present invention provides a calcium carbonate and vitamin D 3 water-free swallowable granules, comprising a main drug granule and a flavoring agent, wherein the main drug granule is made from the above-mentioned composition.

[0015] The above-mentioned composition or the above-mentioned calcium carbonate and vitamin D 3 water-free swallowable granules, wherein there are no particular restrictions on the type and dosage of the pharmaceutically acceptable excipient, and it can be a pharmaceutically common excipient and a suitable dosage of the excipient. By way of example, the excipient can be selected from one or more of binders such as carboxymethylcellulose sodium, hypromellose, etc., flavoring agents such as sorbitol, maltodextrin, etc., sweeteners such as aspartame, acesulfame potassium, etc.

[0016] The above-mentioned calcium carbonate and vitamin D 3 water-free swallowable granules, wherein the calcium carbonate and vitamin D3 composition can be made into granules by a conventional granulation process in pharmacy to obtain the main drug granule; preferably, the main drug granule is prepared by wet granulation, and the solvent used in wet granulation can be water, ethanol, etc., and the particle size can be 300 - 500 μm, preferably the granules are sized through a 20-mesh sieve.

[0017] The above-mentioned calcium carbonate vitamin D 3 Anhydrous swallowable granules, wherein the weight ratio of the main drug granules to the flavoring agent is not particularly limited, for example, it can be 3:1, 2:1, 1:1, and preferably 3:1

[0018] The above-mentioned calcium carbonate vitamin D 3 Anhydrous swallowable granules, wherein the flavoring agent is selected from one or more of acidulants (such as citric acid, malic acid, fruit acid, etc.), auxiliary sweeteners (such as sorbitol, maltodextrin, sucrose, etc.), sweeteners (such as aspartame, sucralose, etc.), and flavoring agents (such as orange flavoring agent, etc.).

[0019] As a preferred embodiment of the present invention, the above-mentioned calcium carbonate vitamin D 3 Anhydrous swallowable granules, wherein in the unit preparation, calcium carbonate is in the form of Ca 2+ counted as 500 mg, and the vitamin D3 carrier is counted as vitamin D 3 counted as 5 μg.

[0020] Preferably, the calcium carbonate vitamin D of the present invention as described above 3 Anhydrous swallowable granules, wherein the vitamin D3 carrier is selected from the vitamin D3 carrier produced by DSM.

[0021] More preferably, the present invention provides a calcium carbonate vitamin D3 anhydrous swallowable granule. In the unit preparation, Ca 2+ 500 mg, vitamin D 3 5 μg, and its single-dose prescription composition is as follows:

[0022]

[0023] The preparation process is as follows:

[0024] 1. Wet granulation: Mix calcium carbonate, sorbitol, carboxymethylcellulose sodium, aspartame, etc. in a wet granulator to mix the materials. Spray 50% ethanol solution and form the materials into sand-like particles through granulation to ensure the formability of the particles after drying. Select a 20-mesh sieve for wet screening.

[0025] Among them, before mixing, calcium carbonate is sieved through a 100-mesh sieve and sorbitol is pulverized and sieved through a 60-mesh sieve to ensure uniform mixing of the materials.

[0026] 2. Drying: Control the material temperature at 40 - 50 °C, control the drying moisture at the end of granulation at 1% - 3%, and screen the obtained granules through a 20-mesh sieve.

[0027] 3. Final mixing: Add the flavoring auxiliary materials and mix. Among them, before adding the flavoring auxiliary materials, sorbitol is sieved through a 60-mesh sieve and citric acid is pulverized and sieved through a 60-mesh sieve.

[0028] 4. Filling: Ensure the product specification and sample uniformity. If necessary, add appropriate amount of flow aid, such as micro powder silica gel or talcum powder, to aid flow.

[0029] The invention relates to a novel nanostructured carbonic acid molecule having active ingredients of calcium carbonate and vitamin D. 3 The water-free swallowable granules are not only conducive to quick swallowing without water in the mouth, but also have a good taste during the whole process, which improves the compliance of the user. It also solves the problem of traditional calcium carbonate preparations that need to be chewed orally, which is very inconvenient for certain groups of people to take, and solves the problem of vitamin D 3 The problem of poor content uniformity in the preparation. In particular, in the unit preparation, while increasing the calcium carbonate content, the loading amount is smaller than the loading amount of the traditional dosage form (the calcium carbonate vitamin D3 anhydrous swallowable granules of the present invention can be controlled to be no more than 2g per unit preparation, while the loading amount of the existing same type of preparations is generally 3-4g). The anhydrous swallowable granules of the present invention have a small loading amount and are good for the taste, making it more convenient to carry and take, and the specific vitamin D 3 Adding it to the preparation in the form of a carrier can effectively ensure that vitamin D 3 The stability and mixing uniformity of the drug are simple in preparation process, high in production efficiency, and the dosage form is easy to take and carry. It is suitable for a wide range of people and has low production costs. It solves the problems of swallowing difficulties, chewing labor and poor taste of traditional dosage forms. It is helpful for the elderly and children with poor swallowing and chewing abilities to carry and take the drug.

[0030] The calcium carbonate vitamin D3 composition and the anhydrous swallowable granules thereof of the present invention adopt a vitamin D3 carrier for feeding, especially a DSM vitamin D3 carrier. Compared with the prior art technology of using a vitamin D3-B-cyclodextrin inclusion complex or mixing calcium carbonate and vitamin D3 in equal parts by mass, the advantages achieved are mainly manifested in: the vitamin D3 carrier is easy to purchase, or the homemade preparation process is simple, and the vitamin D3 content is uniform, the sample stability is good, and it is easy to store and transport. DETAILED DESCRIPTION

[0031] The following examples are used to further explain or illustrate the content of the present invention. The provided examples should not be construed as limiting the scope of protection of the present invention.

[0032] Embodiment 1:

[0033] According to the dosage of 500 units, the material is dosed:

[0034]

[0035] Preparation process:

[0036] 1. Wet granulation: Mix calcium carbonate, sorbitol, sodium carboxymethyl cellulose, aspartame, etc. in a wet granulator to mix the materials. Add 50% ethanol solution by spraying, and granulate the materials to form sand-like particles to ensure the formability of the particles after drying. Select a 20-mesh sieve for wet screening of the granules.

[0037] Among them, before mixing, calcium carbonate is sieved through a 100-mesh sieve and sorbitol is crushed and sieved through a 60-mesh sieve to ensure uniform mixing of the materials.

[0038] 2. Drying: Control the material temperature at 40 - 50 °C, control the drying moisture at the end of granulation at 1% - 3%, and screen the obtained granules through a 20-mesh sieve.

[0039] 3. Final mixing: Add the flavoring excipients part and mix to obtain calcium carbonate vitamin D3 anhydrous swallowable granules. Among them, before adding the flavoring excipients part, sorbitol is sieved through a 60-mesh sieve and citric acid is crushed and sieved through a 60-mesh sieve.

[0040] 4. Filling: Ensure the product specification filling volume and the uniformity of the samples. If necessary, an appropriate amount of glidant, such as colloidal silica or talc powder, can also be added for flow aid.

[0041] Result: The obtained calcium carbonate vitamin D3 anhydrous swallowable granules have a good taste, the filling volume of a single preparation is less than 2 g, and the detected content of vitamin D 3 is stable and the uniformity is good.

[0042] Example 2

[0043] Prescription:

[0044] For 400 unit doses, charge materials as follows:

[0045]

[0046] Preparation process:

[0047] Mix calcium carbonate, sorbitol, starch 1500, and VD3 carrier in a wet granulator and add 65% ethanol to make soft materials, and screen through a 20-mesh sieve. Dissolve maltodextrin 19D and citric acid in purified water to prepare a 50% top-spray granulation solution. Control the temperature at 40 - 50 °C in a fluidized bed top-spray granulator to top-spray granulate the soft materials. After drying, control the moisture at 1% - 3%. Screen through a 20-mesh sieve, add sorbitol, sodium carboxymethyl cellulose 7H4XF, citric acid, sucralose, and orange flavoring, and mix for 5 min.

[0048] Among them, sorbitol is crushed and sieved through an 80-mesh sieve, and citric acid is crushed and sieved through a 60-mesh sieve.

[0049] The finished product granules are uniform, have a slightly cool taste, are swallowed smoothly, and have a good taste masking effect.

[0050] Example 3

[0051] Charge materials according to 400 unit doses:

[0052] Prescription:

[0053]

[0054] Preparation process:

[0055] The same as the preparation process of Example 2.

[0056] Among them: the particle size of sorbitol in the wet granulation part is below 80 mesh; in the fluidized bed granulation process, the taste masking excipients are used to coat the particles. In the taste correction part, the particle sizes of citric acid and sorbitol after pulverization are required to pass through 60 mesh.

[0057] Result: The taste is uniform, it can be swallowed smoothly without water, and the taste correction effect is good.

Claims

1. A calcium carbonate and vitamin D3 composition, comprising calcium carbonate, vitamin D3 and a pharmaceutically acceptable excipient, characterized in that vitamin D3 is made into the composition with calcium carbonate and a pharmaceutically acceptable excipient in the form of a vitamin D3 carrier.

2. The composition according to claim 1, wherein the vitamin D3 carrier is made from vitamin D3 and an excipient, and the excipient is selected from one or more of hydrogenated vegetable oil, gelatin, starch, sucrose, and tocopherol.

3. The composition according to claims 1-2, wherein in a unit preparation, the dosage of calcium carbonate calculated as calcium can be 200 mg, 250 mg, 500 mg, preferably 500 mg; the dosage of the vitamin D3 carrier calculated as vitamin D3 can be 3 μg, 5 μg, preferably 5 μg.

4. A calcium carbonate and vitamin D 3 anhydrous swallowable granules, comprising a main drug granule and a flavoring agent, wherein the main drug granule is made of the composition described in claims 1-3.

5. The calcium carbonate vitamin D according to claim 4 3 An anhydrous swallowable granule, wherein the pharmaceutically acceptable excipient is selected from one or more of a binder (such as sodium carboxymethyl cellulose, hypromellose, hydroxypropyl cellulose, etc.), an auxiliary sweetening agent (such as sorbitol, maltodextrin, sucrose, etc.), and a sweetening agent (such as aspartame, sucralose, etc.).

6. The calcium carbonate and vitamin D according to claims 4 - 5 3 An anhydrous swallowable granule, wherein the composition is made into the main drug granules by wet granulation.

7. The calcium carbonate and vitamin D according to claims 4 - 6 3 An anhydrous swallowable granule, wherein the weight ratio of the main drug granule to the flavoring agent is 3:1, 2:1, 1:1, etc., preferably 3:

1.

8. The calcium carbonate vitamin D according to claims 4-7 3 An anhydrous swallowable granule, wherein the flavoring agent is selected from one or more of acidulants (such as citric acid, malic acid, fruit acid, etc.), auxiliary sweeteners (such as sorbitol, maltodextrin, sucrose, etc.), sweeteners (such as aspartame, sucralose, etc.), and flavoring agents (such as orange flavoring agent, etc.).

9. The calcium carbonate vitamin D according to claims 4 - 8 3 An anhydrous swallowable granule, wherein in a unit preparation, Ca 2+ is 500 mg and vitamin D 3 is 5 μg.

10. The calcium carbonate vitamin D according to claims 4-9 3 An anhydrous swallowable granule, wherein the vitamin D3 carrier is a DSM vitamin D3 carrier.

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