Pharmaceutical composition capable of improving compression ratio of children's favorite tablets and preparation method of pharmaceutical composition

Abstract

The invention provides a pharmaceutical composition capable of improving the compression ratio of children's favorite tablets and a preparation method thereof, and relates to the technical field of pharmaceutical preparations. The pharmaceutical composition comprises pharmaceutical components and auxiliary materials, wherein the pharmaceutical components comprise the following components in parts by weight: 50-100 parts of medicated leaven, 30-80 parts of fructus aurantii, 30-80 parts of bighead atractylodes rhizome, 40-80 parts of hawthorn, 150-250 parts of rice grain sprout and 150-250 parts of malt; the auxiliary materials comprise the following components in parts by weight: 5-15 parts of a disintegrating agent, 5-10 parts of a surfactant and 1-3 parts of a lubricant. By controlling the mass ratio of all the components, the tablet has good compressibility, meanwhile, the compression ratio of particles can be increased, refined honey is selected as an adhesive in the preparation process, and by controlling the adding amount of the refined honey and the mass ratio of dry extract, the tablet has better stability.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a pharmaceutical composition capable of improving the compression ratio of tablets that children like to eat and a preparation method thereof. Background Art

[0002] The compression characteristics of powders are manifested as a reduction in volume, and a solid compressed body can be formed under a certain pressure. The production and preparation of tablets in the pharmaceutical industry is a typical powder compression process. The compression mechanical behavior of the excipients used in tablets during the compression process varies greatly. Some materials, such as magnesium stearate, calcium carbonate, calcium phosphate, crystalline lactose and sucrose, are consolidated by crushing; while some materials, such as microcrystalline cellulose, stearic acid, sodium chloride and starch, are consolidated by plastic deformation; for raw material mixtures or granules used for tableting, usually two mechanisms are carried out simultaneously. The compression properties of the tablet powder layer directly affect the smoothness of the tableting process. The tablet quality, such as hardness, friability, drug solubility, etc., is also related to the compressibility of the compressed powder and the interaction between particles. Therefore, it is very necessary to study the compression characteristics and mechanisms of the powder.

[0003] The compressibility of powder is the ability of powder to reduce its volume under a certain pressure; the formability of powder is the ability of powder to form a compressed object with a certain mechanical strength. For pharmaceutical powders, compressibility and formability are closely linked. Therefore, the compressibility and formability of powders are referred to as compression formability. Complex deformation processes occur during the compression molding process of powders, including the possibility of compression molding, compactness and firmness during the compression process, which is the result of the combined effects of multiple properties of powders such as elasticity and plasticity. Chinese patent CN1939512A discloses a dispersible tablet that children like to eat. The fine powder of the extract of children like to eat is prepared with Liushenqu (fried), Zhizi (fried), Baizhu (fried), Hawthorn, Rice sprout (fried), and Malt (fried) as raw materials, and an appropriate amount of auxiliary materials are added to make the dispersible tablet that children like to eat, the shell of which completely disintegrates within 3 minutes and reaches a uniform dispersion state. The tablet has the characteristics of rapid disintegration in water and dissolving into a fragrant and sweet solution, which is easier for patients to accept and take. The invention can make the dispersible tablet that children like to eat disintegrate faster by optimizing the auxiliary materials; however, the application does not involve the research on the compressibility, hardness and stability of the tablets.

[0004] Journal literature (Effect of microcrystalline cellulose on compressibility and formability of galla chinensis extract, Cao Hanhan et al., Chinese Herbal Medicine, Vol. 45, Issue 8, April 2014) studied the direct tableting of galla chinensis extract (GCE) mixed with different types of microcrystalline cellulose (AvicelDG, CeolusKG802, CeolusPH301, MCCWJ101) in different proportions. The effects of microcrystalline cellulose on the compressibility and formability of GCE were studied with compression molding parameters such as plastic constant, yield pressure, rapid elastic relaxation, compression ratio, and tensile strength as the evaluation indicators. The laws of the four types of microcrystalline cellulose on the compressibility and formability of GCE were further analyzed to guide the selection of excipient types and optimization of dosage during the prescription design process, and provide a reference for direct tableting of Chinese medicine powders.

[0005] Due to the different tissue structures and complex components of different Chinese medicinal materials, the physical properties of Chinese medicinal powders are complex. In the process of direct tableting of Chinese medicinal powders, auxiliary materials are often required. Excipients are important components of tablets, which can improve the compressibility and formability of tablets. However, there are few studies on improving the compressibility and formability of pediatric tablets. Therefore, it is urgent to develop a pharmaceutical composition with improved compression ratio of pediatric tablets and a preparation method thereof. Summary of the invention

[0006] Based on the deficiencies of the prior art, the present invention aims to provide a pharmaceutical composition and a preparation method for improving the compression ratio of pediatric tablets. The present invention selects excipients and controls the ratio between components to make the obtained pharmaceutical composition have better compressibility and formability, and good stability at high temperature.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions: The present invention provides a pharmaceutical composition capable of improving the compression ratio of a tablet for children, comprising pharmaceutical ingredients and auxiliary materials. The pharmaceutical ingredients include the following components by weight: 50-100 parts of Liushenqu, 30-80 parts of Citrus aurantium, 30-80 parts of Atractylodes macrocephala, 40-80 parts of Crataegus pinnatifida, 150-250 parts of rice sprouts, and 150-250 parts of malt.

[0008] Preferably, the pharmaceutical composition comprises the following components by weight: 80 parts of Liushenqu, 50 parts of Fructus Aurantii Immaturus, 50 parts of Atractylodes macrocephala, 65 parts of Crataegus pinnatifida, 180 parts of Rice sprouts, and 180 parts of Malt.

[0009] The auxiliary materials include 5-15 parts of disintegrant, 5-10 parts of surfactant and 1-3 parts of lubricant by weight.

[0010] Wherein, the disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch; Preferably, the disintegrant is a mixture of cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch.

[0011] More preferably, the mass ratio of the cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch is 2-5:5-8:1-3; Further preferably, the mass ratio of the cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch is 4:6:2.

[0012] The surfactant is selected from one or more of sodium lauryl sulfate, poloxamer and sucrose fatty acid ester; Preferably, the surfactant is a mixture of poloxamer and sucrose fatty acid ester; the mass ratio of the two is 1-3:1-2; More preferably, the mass ratio of the poloxamer to the sucrose fatty acid ester is 1.5:1.

[0013] As some preferred embodiments, the mass ratio of the disintegrant to the surfactant is 1-2:1.

[0014] In some preferred embodiments, the mass ratio of the disintegrant to the surfactant is 2:1, 1.5:1 or 1:1.

[0015] The lubricant is magnesium stearate.

[0016] In a preferred embodiment, the mass ratio of the disintegrant to the surfactant is 2:1.

[0017] The present invention also provides a method for preparing the above-mentioned pharmaceutical composition, comprising the following steps: (1) Take rice sprouts and malt slices, add water and boil them, filter the decoction, concentrate it and prepare an extract; (2) Grinding Liushenqu, Zhizi, Baizhu and Crataegus pinnatifida into fine powder respectively, and mixing them to obtain mixture 1; mixing mixture 1 and the extract of step (1), drying, and grinding them into fine powder again to obtain mixture 2; (3) Mix the mixture 2 with a disintegrant and a surfactant, add refined honey to granulate, dry, add a lubricant and compress into tablets to obtain a pharmaceutical composition.

[0018] The decoction in the above step (1) is performed 2-3 times; preferably, the decoction is performed twice, 4-6 times the amount of water is added in the first decoction, and 3-5 times the amount of water is added in the second decoction; more preferably, the decoction is performed twice, 6 times the amount of water is added in the first decoction, and 4 times the amount of water is added in the second decoction, and the decoction time is 30 minutes.

[0019] The particle size of the fine powder in the above step (2) is 0.15-0.18 mm.

[0020] The mass of refined honey added in the above step (3) is 40-50% of the dry extract, preferably 45%.

[0021] The mass of the dried extract is equal to the mass of the extract × solid content + the mass of the mixture 1.

[0022] Compared with the prior art, the present invention has the following beneficial effects: (1) The present invention uses a mixture of cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch as a disintegrant and a mixture of poloxamer and sucrose fatty acid ester as a surfactant. By controlling the mass ratio of the components and the mass ratio of the disintegrant and the surfactant, the tablet has good compressibility and can increase the compression ratio of the particles. (2) The present invention selects auxiliary materials, uses refined honey as a binder during the preparation process, and controls the mass ratio of the added amount of refined honey to the dry extract, so that the tablets have better stability. DETAILED DESCRIPTION

[0023] The following will be combined with the tables in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0024] Hereinafter, examples and comparative examples of the present invention will be shown to explain the composition of the present invention in more detail, but the present invention is not limited thereto.

[0025] The present invention does not limit the sources of the raw materials used. Unless otherwise specified, the raw materials used in the present invention are common commercial products in the technical field.

[0026] Example 1 A pharmaceutical composition having the function of improving the compression ratio of a tablet for children The pharmaceutical composition consists of pharmaceutical ingredients and excipients: The drug ingredients by weight are as follows: 50 parts of Liushenqu, 30 parts of Fructus Aurantii Immaturus, 30 parts of Atractylodes macrocephala, 40 parts of Crataegus pinnatifida, 150 parts of Rice sprouts, and 150 parts of Malt.

[0027] The auxiliary materials by weight are 5 parts of disintegrant, 5 parts of surfactant and 1 part of lubricant.

[0028] Wherein, the disintegrant is a mixture of cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch in a mass ratio of 2:5:1; The surfactant is a mixture of poloxamer and sucrose fatty acid ester; the mass ratio of the two is 1:1; The lubricant is magnesium stearate; The preparation method of the pharmaceutical composition comprises the following steps: (1) Take rice sprout and malt slices and add water to decoct twice, add 6 times the amount of water for the first decoction and 4 times the amount of water for the second decoction, the decoction time is 30 minutes, filter the decoction, concentrate and prepare the extract; (2) Grinding Liushenqu, Zhizi, Baizhu and Crataegus pinnatifida into fine powder respectively, and mixing them to obtain mixture 1; mixing mixture 1 and the extract of step (1), drying, and grinding them into fine powder again to obtain mixture 2; (3) Mix mixture 2 with a disintegrant and a surfactant, add refined honey (the added mass is 40% of the dry extract) to granulate, dry, add a lubricant and press into tablets to obtain a pharmaceutical composition.

[0029] Example 2 A pharmaceutical composition having the function of improving the compression ratio of a tablet for children The pharmaceutical composition consists of pharmaceutical ingredients and excipients: The drug ingredients by weight are as follows: 100 parts of Liushenqu, 80 parts of Fructus Aurantii Immaturus, 80 parts of Atractylodes macrocephala, 80 parts of Crataegus pinnatifida, 250 parts of Rice sprouts, and 250 parts of Malt.

[0030] The auxiliary materials are 15 parts of disintegrant, 10 parts of surfactant and 3 parts of lubricant by weight.

[0031] Wherein, the disintegrant is a mixture of cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch in a mass ratio of 5:8:2; The surfactant is a mixture of poloxamer and sucrose fatty acid ester; the mass ratio of the two is 3:2; The lubricant is magnesium stearate; The preparation method of the pharmaceutical composition comprises the following steps: (1) Take rice sprout and malt slices and add water to decoct twice, add 6 times the amount of water for the first decoction and 4 times the amount of water for the second decoction, the decoction time is 30 minutes, filter the decoction, concentrate and prepare the extract; (2) Grinding Liushenqu, Zhizi, Baizhu and Crataegus pinnatifida into fine powder respectively, and mixing them to obtain mixture 1; mixing mixture 1 and the extract of step (1), drying, and grinding them into fine powder again to obtain mixture 2; (3) Mix mixture 2 with a disintegrant and a surfactant, add refined honey (the added mass is 50% of the dry extract) to granulate, dry, add a lubricant and press into tablets to obtain a pharmaceutical composition.

[0032] Example 3 A pharmaceutical composition having the function of improving the compression ratio of a tablet for children The pharmaceutical composition consists of pharmaceutical ingredients and excipients: The drug components by weight are as follows: 80 parts of Liushenqu, 50 parts of Fructus Aurantii Immaturus, 50 parts of Atractylodes macrocephala, 65 parts of Crataegus pinnatifida, 180 parts of Rice sprouts, and 180 parts of Malt.

[0033] The auxiliary materials by weight are 12 parts of disintegrant, 6 parts of surfactant and 1 part of lubricant.

[0034] Wherein, the disintegrant is a mixture of cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch in a mass ratio of 4:6:2; The surfactant is a mixture of poloxamer and sucrose fatty acid ester; the mass ratio of the two is 1.5:1; The lubricant is magnesium stearate; The preparation method of the pharmaceutical composition comprises the following steps: (1) Take rice sprout and malt slices and boil them in water twice, add 6 times the amount of water for the first time and 4 times the amount of water for the second time, and boil them for 30 min each time. Filter and concentrate the decoction to obtain an extract; (2) Grinding Liushenqu, Zhizi, Baizhu and Crataegus pinnatifida into fine powder respectively, and mixing them to obtain mixture 1; mixing mixture 1 and the extract of step (1), drying, and grinding them into fine powder again to obtain mixture 2; (3) Mix mixture 2 with a disintegrant and a surfactant, add refined honey (the added mass is 45% of the dry extract) to granulate, dry, add a lubricant and press into tablets to obtain a pharmaceutical composition.

[0035] Comparative Example 1 The difference from Example 3 is that silicon dioxide is replaced by microcrystalline cellulose, and the rest is the same as Example 3.

[0036] Comparative Example 2 The difference from Example 3 is that silicon dioxide is replaced by lactose, and the rest is the same as Example 3.

[0037] Comparative Example 3 The difference from Example 3 is that no surfactant is added, the amount of disintegrant added is 18 parts, and the rest is the same as Example 3.

[0038] Comparative Example 4 The difference from Example 3 is that the mass ratio of disintegrant to surfactant is 1:3, i.e., 4.5 parts of disintegrant and 13.5 parts of surfactant, and the rest is the same as Example 3.

[0039] Comparative Example 5 The difference from Example 3 is that the mass ratio of disintegrant to surfactant is 5:1, i.e., 15 parts of disintegrant and 3 parts of surfactant, and the rest is the same as Example 3.

[0040] Comparative Example 6 The difference from Example 3 is that the amount of refined honey added is 60% of the dry extract, and the rest is the same as Example 3.

[0041] Comparative Example 7 The difference from Example 3 is that the amount of refined honey added is 30% of the dry extract, and the rest is the same as Example 3.

[0042] Effect test 1. Compression ratio Testing method: Bulk density / tapped density is measured using a powder property tester Calculation method: C = (ρ f -ρ0) / ρ f ×100% Where C is the compression ratio, ρ f is the tap density and ρ0 is the loose density.

[0043] The test results are shown in Table 1 below.

[0044] Table 1

[0045] According to the test results in Table 1 above, it can be seen that the pharmaceutical composition prepared by the present invention has a higher compression ratio, while in Comparative Examples 1-3, changing the type of disintegrant or not adding a surfactant will significantly affect the compression ratio of the pharmaceutical composition, and the compression ratio will be significantly reduced; in Comparative Examples 4-5, changing the mass ratio of the disintegrant and the surfactant will also reduce the compression ratio, but it is better than Comparative Examples 1-3; Comparative Examples 6-7 change the amount of refined honey added and the content ratio of the dry extract, which will significantly reduce the compression ratio of the pharmaceutical composition.

[0046] 2. Tablet hardness, disintegration time, thickness and color difference detection Testing method: ①Hardness is tested by hardness tester ②Disintegration time is tested by lifting disintegration instrument ③Thickness is tested by vernier caliper ④Color difference is tested by colorimeter The Xiaoerxishi tablets provided in Examples 1-3 and Comparative Examples 1-7 were subjected to stability tests. First, the hardness, disintegration time, and tablet thickness of each tablet were tested when it was just prepared (day 0), and then each packaged tablet was placed in a temperature of 40°C and a humidity of 75% for 6 months (day 180), and the hardness, disintegration time, tablet thickness growth rate, and color difference of the tablets after 6 months of placement were checked. The test results are shown in Table 2 below.

[0047] Table 2

[0048] According to the test results in Table 2 above, it can be seen that the pharmaceutical composition prepared by the present invention has higher stability, hardness, disintegration time and tablet thickness all meet the requirements, and the color difference changes less; while in Comparative Examples 1-3, changing the type of disintegrant or not adding a surfactant will significantly affect the stability of the pharmaceutical composition, especially in Comparative Example 3, not adding a surfactant will significantly increase the color difference of the drug and significantly reduce the stability; in Comparative Examples 4-5, changing the mass ratio of disintegrant and surfactant will also affect the stability of the pharmaceutical composition; in Comparative Examples 6-7, changing the amount of refined honey added and the content ratio of the extract dry paste will reduce the stability of the pharmaceutical composition to varying degrees.

[0049] The above is only a preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment, it is not used to limit the present invention. Any technician familiar with this patent can make some changes or modify the technical contents suggested above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the solution of the present invention.

Claims

1. A pharmaceutical composition having the function of improving the compression ratio of a tablet for children, characterized in that: The pharmaceutical composition comprises pharmaceutical ingredients and excipients. The pharmaceutical ingredients comprise the following components by weight: 50-100 parts of Liushenqu, 30-80 parts of Citrus aurantium, 30-80 parts of Atractylodes macrocephala, 40-80 parts of Crataegus pinnatifida, 150-250 parts of rice sprouts and 150-250 parts of malt; the excipients comprise 5-15 parts of disintegrants, 5-10 parts of surfactants and 1-3 parts of lubricants by weight; the disintegrant is a mixture of cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch in a mass ratio of 2-5:5-8:1-3; the surfactant is a mixture of poloxamer and sucrose fatty acid esters in a mass ratio of 1-3:1-2; the mass ratio of the disintegrant to the surfactant is 1-2:

1.

2. The pharmaceutical composition according to claim 1, characterized in that: The mass ratio of the cross-linked polyvinylpyrrolidone, silicon dioxide and high-amylose corn starch is 4:6:

2.

3. The pharmaceutical composition according to claim 1, characterized in that: The mass ratio of the poloxamer to the sucrose fatty acid ester is 1.5:

1.

4. The pharmaceutical composition according to claim 1, characterized in that: The mass ratio of the disintegrant to the surfactant is 2:1, 1.5:1 or 1:

1.

5. The method for preparing the pharmaceutical composition according to any one of claims 1 to 4, characterized in that: The steps include: (1) Take rice sprouts and malt slices, add water and boil them, filter the decoction, concentrate it and prepare an extract; (2) Grinding Liushenqu, Zhizi, Baizhu and Crataegus pinnatifida into fine powder respectively, and mixing them to obtain mixture 1; mixing mixture 1 and the extract of step (1), drying, and grinding them into fine powder again to obtain mixture 2; (3) Mix the mixture 2 with a disintegrant and a surfactant, add refined honey to granulate, dry, add a lubricant and compress into tablets to obtain a pharmaceutical composition.

6. The preparation method according to claim 5, characterized in that: The decoction in step (1) is performed in 2-3 times.

7. The preparation method according to claim 5, characterized in that: The decoction is performed in two times, with 4-6 times the amount of water added in the first decoction and 3-5 times the amount of water added in the second decoction; the decoction time is 30 minutes.

8. The preparation method according to claim 5, characterized in that: The mass of refined honey added in step (3) is 40-50% of the dry extract.

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