Sucrose iron oxyhydroxide chewable tablet and preparation method thereof

Abstract

The invention discloses a sucrose iron oxyhydroxide chewable tablet and a preparation method thereof. According to the invention, dry granulation is adopted, colloidal silicon dioxide is used as a glidant, magnesium stearate and talcum powder are used as a lubricant, so that the fluidity of the material is improved, and magnesium stearate is sprayed in the tabletting process, so that the problem that chewable tablets are easy to astringent in the tabletting process is effectively solved, and the sucrose iron oxyhydroxide chewable tablets are prepared. The sucrose iron oxyhydroxide chewable tablet disclosed by the invention is complete and smooth in appearance, uniform in color, suitable in hardness and wear resistance and suitable for clinical application.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a sucrose hydroxyl ferric oxide chewable tablet and a preparation method thereof. BACKGROUND

[0002] Hyperphosphatemia refers to a condition in which the phosphate concentration in the blood is higher than the normal level, which is a common complication in patients with chronic kidney disease or end-stage renal disease with severely impaired kidney function. Hyperphosphatemia itself has no obvious symptoms, but a long-term high phosphate concentration in the blood can affect calcium phosphate deposition, causing hypocalcemia, and further causing secondary hyperthyroidism, renal osteopathy and other diseases, and can also cause serious cardiovascular complications. Kidney is an important organ responsible for regulating phosphate balance, and when the kidney function is severely impaired, phosphate cannot be fully excreted from the body. Therefore, hyperphosphatemia is also a common condition in patients with chronic kidney disease (CKD), especially hemodialysis patients.

[0003] Currently approved phosphate binders for the treatment of hyperphosphatemia include calcium-based, lanthanum-based and anion exchange resin products. Sucrose hydroxyl ferric oxide chewable tablet is the first iron-based phosphate binder, which has strong phosphate binding capacity, high blood phosphorus standard rate, does not affect the absorption of vitamin D, reduces the burden of intravenous medication, has a small amount of iron absorption, maintains stable iron parameters, reduces iron supplement and other advantages. The iron (III)-ferric hydroxide in the product is almost insoluble, and has high phosphate adsorption capacity and low iron release.

[0004] Sucrose hydroxyl ferric oxide chewable tablet is developed by Vifor Fresenius, and the trade name is Velphoro, and the specification is 0.5g (calculated as Fe). In the United States, the European Union and Japan, there are related products on the market, and the domestic has approved the original research import. The patent CN201480065206.0 of Vifor discloses a prescription preparation method of sucrose hydroxyl ferric oxide chewable tablet, and the preparation method of the chewable tablet is a powder direct compression process. The raw material with a particle size D50 less than 40um is used to prepare the prescription by the powder direct compression process, and there is a bitter rush phenomenon during tabletting, so it is necessary to optimize the prescription process of sucrose hydroxyl ferric oxide chewable tablet to improve the bitter rush phenomenon during tabletting. SUMMARY

[0005] The purpose of the present application is to provide a sucrose hydroxyl ferric oxide chewable tablet and a preparation method thereof, which can effectively improve the bitter rush phenomenon during tabletting in the prescription preparation process.

[0006] The present application is implemented by the following technical means:

[0007] The present application provides a sucrose hydroxyl ferric oxide chewable tablet, which is prepared by adding a lubricant to a total mixture after dry granulation of sucrose hydroxyl ferric oxide, a glidant, a lubricant, a flavoring agent and a room fragrance agent.

[0008] The sucrose hydroxyl ferric oxide chewable tablet is composed of the following ingredients by weight ratio:

[0009] Sucrose hydroxyl ferric oxide 2000-2500 parts

[0010] Glidant 10-20 parts

[0011] Lubricant 20-40 parts

[0012] Flavoring agent 30-50 parts

[0013] Fragrance 10-20 parts

[0014] Further, the sucrose hydroxyl ferric oxide contains a mixture of hydroxyl ferric oxide (III), sucrose and one or more starches, and the particle size distribution D50 thereof should be less than 40 μm.

[0015] Further, the glidant is colloidal silicon dioxide.

[0016] Further, the lubricant is one or more of magnesium stearate, calcium stearate, sodium stearate fumarate, and talc.

[0017] The present application also provides a preparation method for the above-mentioned sucrose hydroxyl ferric oxide chewable tablet, which specifically comprises the following steps:

[0018] (1) Premixing: uniformly mix the sucrose hydroxyl ferric oxide, glidant, lubricant, flavoring agent, and fragrance;

[0019] (2) Dry granulation: dry granulate the premixing material of step (1) and sieve the granules through an 80-100 mesh screen;

[0020] (3) Total mixing: mix the granules prepared in step (2) with the lubricant to obtain the total mixing material;

[0021] (4) Tabletting: tablet the total mixing material obtained in step (3), and spray magnesium stearate during the tabletting process.

[0022] The present application has the following advantages:

[0023] The sucrose hydroxyl ferric oxide chewable tablet preparation method provided by the present application uses raw material drugs with a particle size distribution D50 of less than 40 μm to prepare the prescription, which improves the problem of too small particle size of the raw material drugs through the dry granulation process, and uses magnesium stearate and talc as lubricants, and sprays magnesium stearate during the tabletting process, which effectively improves the chocking phenomenon during the tabletting process. DETAILED DESCRIPTION

[0024] The following examples provide a detailed description of the formulation of the sucrose iron oxyhydroxide chewable tablets provided by the present invention. However, the present invention is not limited to the following examples. Any methods and materials similar or equivalent to those described herein may be applied to the methods of the present invention. The preferred methods and materials described herein are for illustrative purposes only.

[0025] Unless otherwise specified, the experiments were conducted under conventional conditions or manufacturer's recommended conditions. Reagents and instruments used without manufacturer's indication were commercially available. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those familiar to those skilled in the art.

[0026] Example 1

[0027] A sucrose iron oxyhydroxide chewable tablet, the prescription content is shown in Table 1:

[0028] Table 1

[0029]

[0030] The preparation method of the sucrose iron oxyhydroxide chewable tablets comprises the following steps:

[0031] (1) Mixing:

[0032] ① Premix 1: Weigh the prescribed amount of colloidal silicon dioxide, raspberry essence, gum arabic, and 20% of the prescribed amount of sucrose ferric oxyhydroxide, mix and sieve to obtain premix 1;

[0033] ② Premix 2: Weigh the remaining 80% of the prescribed amount of sucrose ferric oxyhydroxide, add it to premix 2, mix and sieve to obtain premix 2;

[0034] ③. Premix 3: Take 15% of premix 3 and the prescribed amount of talc powder, mix and sieve; add the above mixed powder and the remaining 85% of premix 2 into a mixer, mix and sieve to obtain premix 3;

[0035] (2) Granulation: Add the above mixture 3 into a dry granulator for granulation, and pass the prepared granules through an 80-mesh sieve;

[0036] (3) Total mixing: Add the prescribed amount of magnesium stearate to the granules after granulation and mix using a hopper mixer;

[0037] (4) Tableting: Add the above mixture into a rotary tablet press for tableting with a hardness of 100 to 260 N; spray magnesium stearate during the tableting process at a spraying rate of ≥100 g / h.

[0038] Example 2

[0039] A sucrose hydroxyl ferric oxide chewable tablet, the prescription content is shown in Table 2:

[0040] Table 2

[0041]

[0042]

[0043] The preparation method of the sucrose hydroxyl ferric oxide chewable tablet is the same as that of Example 1 Example 3

[0044] A sucrose hydroxyl ferric oxide chewable tablet, the prescription content is shown in Table 3:

[0045] Table 3

[0046]

[0047] The preparation method of the sucrose hydroxyl ferric oxide chewable tablet is the same as that of Example 1 Example 4

[0048] A sucrose hydroxyl ferric oxide chewable tablet, the prescription content is shown in Table 4:

[0049] Table 4

[0050]

[0051] The preparation method of the sucrose hydroxyl ferric oxide chewable tablet is the same as that of Example 1 Example 5

[0052] A sucrose hydroxyl ferric oxide chewable tablet, the prescription content is shown in Table 5:

[0053] Table 5

[0054]

[0055]

[0056] The preparation method of the sucrose hydroxyl ferric oxide chewable tablet is the same as that of Example 1

[0057] Comparative Example 1

[0058] A sucrose hydroxyl ferric oxide chewable tablet, the prescription content is shown in Table 6:

[0059] Table 6

[0060] Ingredient Name Action Prescribed Amount / g Sucrose Iron Oxide Hydroxyl Active Ingredient 2500 Colloidal Silicon Dioxide Glidant 20 Talc Lubricant 15 Magnesium Stearate Lubricant 15 Raspberry Flavor Flavoring Agent 30 Gum Arabic Perfume Retainer 10

[0061] The preparation method of the sucrose hydroxyl ferric oxide chewable tablet comprises the following steps:

[0062] (1) Mixing:

[0063] ①, Pre-mixture 1: take the prescription amount of colloidal silicon dioxide, raspberry essence, gum arabic and 20% of the prescription amount of sucrose hydroxyl ferrite, mix and sieve, get pre-mixture 1;

[0064] ②, Pre-mixture 2: take the remaining 80% of the prescription amount of sucrose hydroxyl ferrite, add to pre-mixture 2 and mix and sieve, get pre-mixture 2;

[0065] ③, Pre-mixture 3: take 15% of pre-mixture 3 and the prescription amount of talc powder, mix and sieve; the above mixed powder and the remaining 85% of pre-mixture 2 are added to the mixer and mixed and sieved to get pre-mixture 3;

[0066] (2) tabletting: the above mixture is added to the rotary tablet press for tabletting, hardness 100-260N.

[0067] Comparative example 2

[0068] A sucrose hydroxyl ferrite chewable tablet, the prescription content is shown in table 7:

[0069] Table 7

[0070]

[0071] The preparation method of the sucrose hydroxyl ferrite chewable tablet, comprising the following steps:

[0072] (1) mixing:

[0073] ①, Pre-mixture 1: take the prescription amount of colloidal silicon dioxide, raspberry essence, gum arabic and 20% of the prescription amount of sucrose hydroxyl ferrite, mix and sieve, get pre-mixture 1;

[0074] ②, Pre-mixture 2: take the remaining 80% of the prescription amount of sucrose hydroxyl ferrite, add to pre-mixture 2 and mix and sieve, get pre-mixture 2;

[0075] ③, Pre-mixture 3: take 15% of pre-mixture 3 and the prescription amount of talc powder, mix and sieve; the above mixed powder and the remaining 85% of pre-mixture 2 are added to the mixer and mixed and sieved to get pre-mixture 3;

[0076] (2), granulation: the above mixture 3 is added to the dry granulator for granulation;

[0077] (3), total mixing: add the prescription amount of magnesium stearate to the prepared granules and mix using a hopper mixer;

[0078] (4), tabletting: the above mixture is added to the rotary tablet press for tabletting, hardness 100-260N; spray magnesium stearate during tabletting, spraying rate ≥100g / h.

[0079] Comparative Example 3

[0080] A sucrose ferric oxyhydroxide chewable tablet, the prescription content is shown in Table 8:

[0081] Table 8

[0082]

[0083] The preparation method of the sucrose ferric oxyhydroxide chewable tablet, comprising the following steps:

[0084] (1) mixing:

[0085] ①, pre-mixture 1: take the prescription amount of colloidal silicon dioxide, raspberry essence, gum arabic and 20% of the prescription amount of sucrose ferric oxyhydroxide, mix and sieve, to obtain pre-mixture 1;

[0086] ②, pre-mixture 2: take the remaining 80% of the prescription amount of sucrose ferric oxyhydroxide, add to the pre-mixture 2, mix and sieve, to obtain pre-mixture 2;

[0087] ③, pre-mixture 3: take 15% pre-mixture 3 and prescription amount of talc, mix and sieve; the above mixed powder and the remaining 85% pre-mixture 2 are added to the mixer and mixed and sieved to obtain pre-mixture 3;

[0088] (2), granulation: the above mixture 3 is added to the dry granulator for granulation, and the prepared granules are sieved through an 80 mesh screen;

[0089] (3), total mixing: the sieved granules are added to the prescription amount of magnesium stearate, and the hopper mixer is used for mixing;

[0090] (4), tabletting: the above mixture is added to the rotary tablet press for tabletting, and the hardness is 100-260N.

[0091] Table 9 Evaluation results of sucrose ferric oxyhydroxide chewable tablets obtained in examples and comparative examples

[0092]

[0093]

[0094] It can be seen that the sucrose ferric oxyhydroxide chewable tablet provided by the present application has more uniform and smooth color on the tablet surface, and good appearance compared with the comparative example. After mixing the raw material with small particle size, the tabletting process is serious, and the finished product has side flower tablet; after dry granulation, the tabletting process has astringent and flushing phenomenon, and the tablet surface has a large number of dark spots; the tabletting process does not spray magnesium stearate, and the tabletting process has astringent and flushing phenomenon, and the finished product has dark marks on the side.

[0095] Therefore, based on the prior art, when the raw medicine with the particle size D50 less than 40 microns is used to prepare a prescription, the caking phenomenon in the tabletting process can be effectively improved by the dry granulation screening, tabletting process and magnesium stearate spraying, and the prepared tablet has a complete and smooth appearance and uniform color.

[0096] The preferred embodiments of the present application have been described above with the preferred embodiments, but the present application is not limited to the above examples, and various modifications and changes can be made by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A sucrose iron oxyhydroxide chewable tablet, characterized in that: The tablet is prepared by dry granulation and then tabletting, wherein the ingredients include 2000-2500 parts of sucrose ferric oxyhydroxide, 10-20 parts of a glidant, 20-40 parts of a lubricant, 30-40 parts of a flavoring agent, and 10-20 parts of a fragrance retaining agent.

2. The sucrose iron oxyhydroxide chewable tablet according to claim 1, characterized in that: The sucrose ferric oxyhydroxide comprises a mixture of ferric oxyhydroxide (III), sucrose and one or more starches, and its particle size distribution D50 should be less than 40 μm.

3. The sucrose iron oxyhydroxide chewable tablet according to claim 1, characterized in that: The glidant is colloidal silicon dioxide.

4. The sucrose iron oxyhydroxide chewable tablet according to claim 1, characterized in that: The lubricant is one or more of magnesium stearate, calcium stearate, sodium stearyl fumarate and talc.

5. The method for preparing a sucrose iron oxyhydroxide chewable tablet according to claim 1, characterized in that: The following steps are involved: (1) Premixing: Mix sucrose ferric oxyhydroxide, glidant, lubricant, flavoring agent and aroma agent evenly; (2) Dry granulation: taking the premix of step (1) and performing dry granulation; (3) Total mixing: mixing the granules prepared in step (2) with a lubricant to obtain a total mixture; (4) Tableting: The total mixture obtained in step (3) is tableted.

6. The method for preparing a sucrose iron oxyhydroxide chewable tablet according to claim 1, characterized in that: The step (2) adopts dry granulation, and after dry granulation, the granules need to be sieved through a 60-100 mesh screen.

7. The method for preparing a sucrose iron oxyhydroxide chewable tablet according to claim 1, characterized in that: During the tableting process in step (3), magnesium stearate needs to be sprayed at a rate greater than or equal to 100 g / h.

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