CN113456665A - Calcium carbonate chewable tablet pharmaceutical composition and preparation method thereof - Google Patents
Calcium carbonate chewable tablet pharmaceutical composition and preparation method thereof Download PDFInfo
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- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A61K9/2022—Organic macromolecular compounds
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- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/02—Nutrients, e.g. vitamins, minerals
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Abstract
The invention belongs to the technical field of pharmaceutical preparations, and relates to a calcium carbonate chewable tablet pharmaceutical composition, which comprises the following components in part by weight: calcium carbonate, filler, adhesive, flavoring agent, colorant and lubricant. The filling agent is one of sorbitol and mannitol, the adhesive is povidone K30, the flavoring agent is aspartame and orange powder essence, the coloring agent is lemon yellow, and the lubricating agent is magnesium stearate, and the filling agent is characterized in that: the pharmaceutical formulation further comprises a disintegrant. Compared with the prescription composition of the marketed product, the disintegrating agent is added on the basis of the prescription composition, so that the disintegrating property and the dissolution property of the marketed product can be obviously improved, the product can be ensured to have good release and shorter disintegrating time in the 0-day and stability processes, the product can be ensured to be safe and effective to take, and the problems of potential safety hazard and poor effect of the marketed product are solved.
Description
Technical Field
The invention belongs to the technical field of medicines, and relates to a calcium carbonate chewable tablet pharmaceutical composition and a preparation method thereof.
Background
Calcium carbonate is an important regulator of bone metabolism, and can maintain normal excitability of nerves and muscles and reduce permeability of capillaries. It can be used for preventing and treating calcium deficiency, such as osteoporosis, tetany, bone dysplasia, rickets, and calcium supplement for children, pregnant women, lactating women, menopausal women, and the elderly.
Calcium carbonate chewable tablets were first approved for marketing in the united kingdom in 1987 at 11 months, mainly for: (1) supplementation of high normal demand or dietary calcium deficiency; (2) can be used for the adjuvant treatment of osteoporosis; (3) can be used as phosphate binder in renal dialysis treatment of renal failure patients. Calcium carbonate is available in various dosage forms, mainly including tablets, capsules, granules, chewable tablets, effervescent tablets and the like, wherein the chewable tablets are convenient to take, are not limited by time and place, can be taken on time even under the condition of water shortage, and are particularly suitable for children, patients with dysphagia or poor gastrointestinal function. At present, calcium carbonate chewable tablets are marketed in the uk in two specifications: 500mg and 1500 mg. At present, no originally ground calcium carbonate chewable tablets are imported and sold in the market at home. Calcium carbonate chewable tablets from a plurality of imitation manufacturers on the market in China, such as Sanjiu ai De Fu pharmaceutical Co., Ltd, Shanxi step pharmaceutical Co., Ltd, Zhejiang Hazheng pharmaceutical Co., Ltd, and the like. Through investigation, no disintegrant is available in the prescription composition of the calcium carbonate chewable tablets sold in the market, including the original prescription preparation, so that the problems of slow disintegration time limit and slow dissolution rate in the placing process commonly exist in the calcium carbonate chewable tablets sold in the market at present, and the problems are specifically shown in the following steps: the sample with 0-day and placement stability has long disintegration time limit and low dissolution rate, so the disintegration time limit and the dissolution rate cannot be determined into the quality standard, and the evaluation requirement cannot be met.
The united states Food and Drug Administration (FDA) explicitly requires that chewable tablets have good disintegration properties and high dissolution rate in the guidelines on chewable tablets published in 2016, so as to avoid the problem of poor safety and efficacy when patients do not chew or do not chew sufficiently; the national Center for Drug Examination (CDE) refers to FDA chewable tablet guiding principles, and clearly requires that the chewable tablet limits the dissolution rate and disintegration time to the standard of shelf life.
In summary, the prior calcium carbonate chewable tablet pharmaceutical preparation has the technical problems that: (1) in the sample placing process, the disintegration time limit of the sample is lengthened, the dissolution rate is slowed, the disintegration time limit and the dissolution rate cannot be determined into the quality standard, and the evaluation requirement of the current CDE cannot be met; (2) calcium carbonate chewable tablets sold in China at present are difficult to evaluate by the consistency of a counterfeit medicine.
Therefore, the above problems need to be solved by selecting appropriate recipes and processes. The invention provides a calcium carbonate chewable tablet and a preparation process thereof, which can solve the problem that the disintegration time limit and the dissolution rate of the existing chewable tablet are slowed down in the placing process, have the advantages of easy disintegration, good dissolution performance, good drug stability, good safety performance and the like, and can meet the current evaluation requirements.
Disclosure of Invention
The invention aims to provide a formula composition of a calcium carbonate chewable tablet, which is prepared from easily available materials and suitable for domestic industrial production, has good release and shorter disintegration time, and can meet the current evaluation requirement.
Specifically, the invention is mainly realized by the following technical scheme:
a pharmaceutical composition of calcium carbonate chewable tablets comprises the following components by weight: calcium carbonate, filler, adhesive, flavoring agent, colorant and lubricant. The filling agent is one of sorbitol and mannitol, the adhesive is povidone K30, the flavoring agent is aspartame and orange powder essence, the coloring agent is lemon yellow, and the lubricating agent is magnesium stearate.
The pharmaceutical composition is characterized by further comprising a disintegrant compared with the prescription composition of the marketed product.
The disintegrant is one of croscarmellose sodium, crospovidone and carboxymethyl starch sodium, preferably crospovidone.
The dosage range of the disintegrating agent is 0-10% (W/W), and the preferred dosage range is 4-8% (W/W).
The preparation method of the sodium carbonate chewable tablet pharmaceutical preparation comprises the following steps: preparing calcium carbonate, disintegrant, colorant and adhesive into soft mass, granulating, drying wet granules, mixing the dried granules with filler, correctant and lubricant, and tabletting.
The specific preparation process comprises the following steps:
1) pretreatment: sieving the auxiliary materials with a 30-mesh sieve, and removing lumps for later use;
2) preparing an adhesive: binder concentration 20%: adding povidone K30 of a prescription amount into a proper amount of purified water, stirring while adding, adopting a heat-preservation stirring barrel, adding lemon yellow of the prescription amount after completely dissolving, continuously stirring for 20min, and then standing for 10 min;
3) a granulation step: 1. uniformly mixing the raw material medicine and the disintegrating agent in a wet granulator; 2. adding the adhesive solution into a wet granulator under high-speed stirring and shearing (60 s); granulating, drying and finishing;
4) a total mixing step: specifically, the particles obtained in the step 3) and additional auxiliary materials are uniformly mixed to obtain total mixed particles;
5) tabletting: specifically, the granules obtained in the step 4) are pressed into tablets by a tablet press.
Advantageous effects
Research results show that the disintegrating agent with a specific dosage ratio is added, and compared with the prior art, the disintegrating agent has the beneficial technical effects that: (1) the problem that the disintegration time limit and the dissolution rate become slow in the process of placing the calcium carbonate chewable tablet can be effectively solved, the calcium carbonate chewable tablet medicine composition is easy to disintegrate, has good dissolution performance, meets the current evaluation requirement, and can smoothly pass the consistency evaluation of the imitation drugs; (2) the main adverse reactions of the chewable tablet comprise gastrointestinal tract blockage caused by swallowing or incomplete chewing of a patient, esophagus stimulation and the like.
Detailed Description
The following examples are presented to further illustrate the claimed embodiments and are not intended to limit the invention.
Example 1:
the preparation process comprises the following steps:
1) pretreatment: sieving the auxiliary materials with a 30-mesh sieve, and removing lumps for later use;
2) preparing an adhesive: binder concentration 20%: adding povidone K30 of a prescription amount into a proper amount of purified water, stirring while adding, adopting a heat-preservation stirring barrel, adding lemon yellow of the prescription amount after completely dissolving, continuously stirring for 20min, and then standing for 10 min;
3) a granulation step: 1. uniformly mixing the raw material medicines and the croscarmellose sodium in a wet granulator; 2. adding the adhesive solution into a wet granulator under high-speed stirring and shearing (60 s); granulating, drying and finishing;
4) a total mixing step: specifically, the particles obtained in the step 3) and additional auxiliary materials are uniformly mixed to obtain total mixed particles;
5) tabletting: specifically, the granules obtained in the step 4) are pressed into tablets by a tablet press.
Example 2:
the preparation process comprises the following steps:
1) pretreatment: sieving the auxiliary materials with a 30-mesh sieve, and removing lumps for later use;
2) preparing an adhesive: binder concentration 20%: adding povidone K30 of a prescription amount into a proper amount of purified water, stirring while adding, adopting a heat-preservation stirring barrel, adding lemon yellow of the prescription amount after completely dissolving, continuously stirring for 20min, and then standing for 10 min;
3) a granulation step: 1. mixing the raw materials and carboxymethyl starch sodium in a wet granulator; 2. adding the adhesive solution into a wet granulator under high-speed stirring and shearing (60 s); granulating, drying and finishing;
4) a total mixing step: specifically, the particles obtained in the step 3) and additional auxiliary materials are uniformly mixed to obtain total mixed particles;
example 3:
the preparation process comprises the following steps:
1) pretreatment: sieving the auxiliary materials with a 30-mesh sieve, and removing lumps for later use;
2) preparing an adhesive: binder concentration 20%: adding povidone K30 of a prescription amount into a proper amount of purified water, stirring while adding, adopting a heat-preservation stirring barrel, adding lemon yellow of the prescription amount after completely dissolving, continuously stirring for 20min, and then standing for 10 min;
3) a granulation step: 1. uniformly mixing the raw material medicine and the crospovidone in a wet granulator; 2. adding the adhesive solution into a wet granulator under high-speed stirring and shearing (60 s); granulating, drying and finishing;
4) a total mixing step: specifically, the particles obtained in the step 3) and additional auxiliary materials are uniformly mixed to obtain total mixed particles;
5) tabletting: specifically, the granules obtained in the step 4) are pressed into tablets by a tablet press.
Comparative examples
The prescription is not added with disintegrant
The preparation process comprises the following steps:
1) pretreatment: sieving the auxiliary materials with a 30-mesh sieve, and removing lumps for later use;
2) preparing an adhesive: binder concentration 20%: adding a proper amount of 95% ethanol into povidone K30 according to the formula amount, stirring while adding, adopting a heat-preservation stirring barrel, adding lemon yellow according to the formula amount after completely dissolving, continuously stirring for 20min, and then standing for 10 min;
3) a granulation step: 1. putting the raw material medicines into a wet granulator, and adding the adhesive solution into the wet granulator under the condition of high-speed stirring and shearing (for 60 s); granulating, drying and finishing;
4) a total mixing step: specifically, the particles obtained in the step 3) and additional auxiliary materials are uniformly mixed to obtain total mixed particles;
5) tabletting: specifically, the granules obtained in the step 4) are pressed into tablets by a tablet press.
Test example 1: a routine examination of calcium carbonate tablets is given in the following table:
TABLE 1 examination results of calcium carbonate chewable tablets
Note: the dissolution rate detection method is 900ml of 0.1mol/L hydrochloric acid medium, 75 rpm by a paddle method and 30 minutes of dissolution data;
and (4) conclusion:
1) compared with the comparative examples, the examples 1, 2 and 3 have the advantages that the granule state, the tabletting process, the hardness, the friability and the mouthfeel are basically consistent;
2) the property difference of 0 day between the embodiment and the comparative example is larger, namely the disintegration time and the dissolution rate, the disintegration time of the embodiment is within 8min, and the disintegration time of the comparative example is more than 15 min;
3) compared with the comparative examples, the dissolution rates in 0 day are different to each other, the dissolution rates in the comparative examples (without a disintegrant prescription) are only 70%, the dissolution rates in examples 1, 2 and 3 are all 95% or more, and the difference is more than 25%.
Test example 2: stability test
Taking the examples 1, 2 and 3 and the comparative example 2 of the invention, according to the guidelines of stability tests of XIXC bulk drugs and pharmaceutical preparations which are addendum in the Chinese pharmacopoeia 2015 year edition, carrying out accelerated stability test after sealed packaging under the conditions of 40 ℃ plus or minus 2 ℃ and RH 75% plus or minus 5%, and sampling at 0 month, 1 month, 2 months and 3 months after standing to test the physicochemical properties, wherein the results are shown in Table 3.
TABLE 5 stability test results of calcium carbonate tablets
And (4) conclusion:
the stability results of examples 1, 2 and 3 are very different from those of the comparative examples: in the stability process, the disintegration time and the dissolution rate of the samples prepared in the examples 1, 2 and 3 are not obviously changed, but the disintegration time of the comparative example is prolonged by more than 25min, and the dissolution rate is reduced by more than 60%.
The results of the comprehensive test 1 and the test 2 show that the sample prepared by the method has good quality in 0 day and the stability process, the result meets the CDE declaration requirement, and the safety and the effectiveness of the product can be ensured.
Claims (4)
1. A calcium carbonate chewable tablet pharmaceutical composition comprising: calcium carbonate, a filling agent, a binding agent, a flavoring agent, a coloring agent and a lubricating agent, wherein the filling agent is one of sorbitol and mannitol, the binding agent is povidone K30, the flavoring agent is aspartame and orange powder essence, the coloring agent is lemon yellow, and the lubricating agent is magnesium stearate, and the calcium carbonate is characterized in that: the pharmaceutical composition further comprises a disintegrant.
2. A calcium carbonate chewing tablet pharmaceutical composition according to claim 1, wherein said disintegrant is one of croscarmellose sodium, crospovidone, and sodium starch glycolate, preferably crospovidone.
3. A pharmaceutical composition of calcium carbonate chewable tablets according to claim 2, characterized in that said disintegrant is present in an amount ranging from 0% to 10% (W/W), preferably in an amount ranging from 4% to 8% (W/W).
4. A process for preparing a sodium carbonate chewable tablet pharmaceutical composition according to any one of claims 1 to 3, characterized in that it comprises the following steps: preparing calcium carbonate, disintegrant, colorant and adhesive into soft mass, granulating, drying wet granules, mixing the dried granules with filler, correctant and lubricant, and tabletting.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010235225.0A CN113456665A (en) | 2020-03-30 | 2020-03-30 | Calcium carbonate chewable tablet pharmaceutical composition and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010235225.0A CN113456665A (en) | 2020-03-30 | 2020-03-30 | Calcium carbonate chewable tablet pharmaceutical composition and preparation method thereof |
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| Publication Number | Publication Date |
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| CN113456665A true CN113456665A (en) | 2021-10-01 |
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| CN202010235225.0A Pending CN113456665A (en) | 2020-03-30 | 2020-03-30 | Calcium carbonate chewable tablet pharmaceutical composition and preparation method thereof |
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