Pharmaceutical composition containing ferrous succinate and preparation method of preparation of pharmaceutical composition

Abstract

The invention relates to the technical field of biological medicine, in particular to a medicine composition containing ferrous succinate and a preparation method of a preparation of the medicine composition, and the medicine composition comprises the ferrous succinate, a filling agent, a disintegrating agent, an adhesive and a lubricating agent. More specifically, the pharmaceutical composition contains 95-105 parts by weight of ferrous succinate, 60-70 parts by weight of calcium hydrogen phosphate dihydrate as a filler, 150-160 parts by weight of corn starch and succinic acid as disintegrating agents, 17-18 parts by weight of povidone K30 as an adhesive and 3-4 parts by weight of magnesium stearate as a lubricant. The ferrous succinate tablet prepared from the pharmaceutical composition has the advantages that the high iron content is obviously reduced, and the stability and the dissolution rate are better.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and more particularly to a pharmaceutical composition containing ferrous succinate and a preparation method thereof. Technical Background

[0002] When the body's demand for iron is out of balance with its supply, iron stores are depleted, leading to a subsequent lack of iron in red blood cells, ultimately causing iron-deficiency anemia. Iron-deficiency anemia is the final stage of iron deficiency, manifesting as microcytic hypochromic anemia and other abnormalities caused by iron deficiency. Iron-deficiency anemia is the most common form of anemia.

[0003] The 2020 Report on the Nutrition and Chronic Disease Status of Chinese Residents shows that the anemia rate among Chinese residents aged 18 and over is 8.7%, among pregnant women it is 13.6%, and among children and adolescents aged 6 to 17 it is 6.1%. Among pregnant women and children, who are the main groups with anemia, iron deficiency causes over 50% of cases. Pregnant women with iron deficiency anemia experience significantly increased rates of cesarean sections and postpartum hemorrhage, and the incidence of low fetal weight and premature birth also increases with the severity of anemia. In children, iron deficiency anemia can affect the development of vital organs, leading to motor impairment, weakened immunity, and cognitive development. Iron deficiency anemia is also a common complication of chronic kidney disease, affecting approximately 42.7% of patients. For patients with chronic kidney disease and iron deficiency anemia, anemia can accelerate the progression of chronic kidney disease and increase the risk of dialysis and cardiovascular events. In addition, due to insufficient blood oxygen, patients are prone to symptoms such as fatigue, irritability, and memory loss, which seriously affect their physical health, quality of life, and work ability. Therefore, timely diagnosis and treatment of iron deficiency anemia is of great clinical significance.

[0004] Iron deficiency anemia is primarily treated with oral iron supplements. Currently, oral iron supplements primarily include first-generation iron supplements, such as ferrous sulfate, and second-generation iron supplements, such as ferrous succinate. Ferrous succinate is unstable and easily oxidizes to ferric iron (hereinafter referred to as "ferric iron"), resulting in poor stability. Therefore, developing a stable ferrous succinate preparation is of great significance. Summary of the Invention

[0005] Based on the above reasons, the applicant, after several creative efforts, has obtained a new pharmaceutical composition containing ferrous succinate as the active ingredient. The pharmaceutical composition contains 95-105 parts by weight of ferrous succinate, 60-70 parts by weight of calcium hydrogen phosphate dihydrate as a filler, 150-160 parts by weight of corn starch and succinic acid as disintegrants, 17-18 parts by weight of povidone K30 as a binder, and 3-4 parts by weight of magnesium stearate as a lubricant. This pharmaceutical composition is used to prepare ferrous succinate tablets with significantly reduced iron content, better stability, and better solubility.

[0006] The present invention is achieved through the following technical solutions.

[0007] A pharmaceutical composition containing ferrous succinate comprises ferrous succinate, a filler, a disintegrant, a binder and a lubricant.

[0008] The pharmaceutical composition containing ferrous succinate comprises 95-105 parts by weight of ferrous succinate, 60-70 parts by weight of a filler, 150-160 parts by weight of a disintegrant, 17-18 parts by weight of a binder, and 3-4 parts by weight of a lubricant.

[0009] The pharmaceutical composition containing ferrous succinate comprises 95-105 parts by weight of ferrous succinate, 60-70 parts by weight of dibasic calcium phosphate dihydrate as a filler, 150-160 parts by weight of corn starch and succinic acid as disintegrants (weight ratio 27:50), 17-18 parts by weight of povidone K30 as a binder, and 3-4 parts by weight of magnesium stearate as a lubricant. Preferably, the composition comprises 100 parts by weight of ferrous succinate, 66 parts by weight of dibasic calcium phosphate dihydrate as a filler, 54 parts by weight of corn starch and 100 parts by weight of succinic acid as disintegrants, 17.5 parts by weight of povidone K30 as a binder, and 3.4 parts by weight of magnesium stearate as a lubricant.

[0010] In the pharmaceutical composition containing ferrous succinate, the weight ratio of the disintegrant corn starch to succinic acid is 27:50.

[0011] The pharmaceutical composition containing ferrous succinate is prepared into a solid preparation.

[0012] The pharmaceutical composition containing ferrous succinate is prepared into tablets, capsules or granules.

[0013] The pharmaceutical composition containing ferrous succinate, wherein the tablet is prepared by:

[0014] (1) The first step is premixing: ferrous succinate, calcium hydrogen phosphate dihydrate, corn starch, and succinic acid are mixed uniformly to obtain a premixed material for use;

[0015] (2) Step 2: Preparation of adhesive solution: Take povidone K30, add it to 60% ethanol, mix well, and set aside;

[0016] (3) The third step, granulation and tableting: take the prepared premixed material mixed in the first step, granulate it with the binder solution, dry the whole granules, add magnesium stearate, mix well, and tablet to obtain ferrous succinate tablets.

[0017] In the pharmaceutical composition containing ferrous succinate, the weight ratio of povidone K30 to 60% ethanol is 7:8.

[0018] The calcium hydrogen phosphate dihydrate of the present invention is also called calcium hydrogen phosphate dihydrate.

[0019] Table 1 Raw material and auxiliary material information

[0020]

[0021] The present invention has the following beneficial technical effects:

[0022] The preparation of the present application has better stability. The influencing factor test shows that the Fe2+ content changes little, the high Fe content meets the requirements of the quality standard, and the solubility is not lower than 90%. DETAILED DESCRIPTION

[0023] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention is further described in detail below in conjunction with specific embodiments. It should be understood that these descriptions are merely exemplary and are not intended to limit the scope of the present invention. In addition, in the following description, descriptions of well-known structures and technologies are omitted to avoid unnecessary confusion of the concept of the present invention.

[0024] Preparation Example 1

[0025] Ferrous succinate 100g, filler calcium hydrogen phosphate dihydrate 66g, disintegrants corn starch 54g, succinic acid 100g, binder povidone K30 17.5g, lubricant magnesium stearate 3.4g.

[0026] The above pharmaceutical composition is prepared into tablets, and the preparation method of the tablets is as follows:

[0027] (1) The first step is premixing: ferrous succinate, calcium hydrogen phosphate dihydrate, corn starch, and succinic acid are mixed uniformly to obtain a premixed material for use;

[0028] (2) The second step is to prepare the adhesive solution: take povidone K30 and add it to 60% ethanol; the weight ratio of povidone K30 to 60% ethanol is 7:8; mix well and set aside;

[0029] (3) The third step, granulation and tableting: take the prepared premixed material mixed in the first step, granulate it with the binder solution, dry the whole granules, add magnesium stearate, mix well, and tablet press to obtain 1000 ferrous succinate tablets.

[0030] Preparation Example 2

[0031] Ferrous succinate 200g, filler calcium hydrogen phosphate dihydrate 132g, disintegrants corn starch 108g, succinic acid 200g, binder povidone K30 35g, lubricant magnesium stearate 6.8g.

[0032] The above pharmaceutical composition is prepared into tablets, and the preparation method of the tablets is as follows:

[0033] (1) The first step is premixing: ferrous succinate, calcium hydrogen phosphate dihydrate, corn starch, and succinic acid are mixed uniformly to obtain a premixed material for use;

[0034] (2) The second step is to prepare the adhesive solution: take povidone K30 and add it to 60% ethanol; the weight ratio of povidone K30 to 60% ethanol is 7:8; mix well and set aside;

[0035] (3) The third step, granulation and tableting: take the prepared premixed material mixed in the first step, granulate it with the binder solution, dry the whole granules, add magnesium stearate, mix well, and tablet press to obtain 2000 ferrous succinate tablets.

[0036] Preparation Example 3

[0037] Ferrous succinate 1000g, filler calcium hydrogen phosphate dihydrate 660g, disintegrants corn starch 540g, succinic acid 1000g, binder povidone K30 175g, lubricant magnesium stearate 34g.

[0038] The above pharmaceutical composition is prepared into tablets, and the preparation method of the tablets is as follows:

[0039] (1) The first step is premixing: ferrous succinate, calcium hydrogen phosphate dihydrate, corn starch, and succinic acid are mixed uniformly to obtain a premixed material for use;

[0040] (2) The second step is to prepare the adhesive solution: take povidone K30 and add it to 60% ethanol; the weight ratio of povidone K30 to 60% ethanol is 7:8; mix well and set aside;

[0041] (3) The third step, granulation and tableting: take the prepared premixed material mixed in the first step, granulate it with the binder solution, dry the whole granules, add magnesium stearate, mix well, and tablet press to obtain 10,000 ferrous succinate tablets.

[0042] Preparation Example 4

[0043] Ferrous succinate 2000g, filler calcium hydrogen phosphate dihydrate 1320g, disintegrants corn starch 1080g, succinic acid 2000g, binder povidone K30 350g, lubricant magnesium stearate 68g.

[0044] The above pharmaceutical composition is prepared into tablets, and the preparation method of the tablets is as follows:

[0045] (1) The first step is premixing: ferrous succinate, calcium hydrogen phosphate dihydrate, corn starch, and succinic acid are mixed uniformly to obtain a premixed material for use;

[0046] (2) The second step is to prepare the adhesive solution: take povidone K30 and add it to 60% ethanol; the weight ratio of povidone K30 to 60% ethanol is 7:8; mix well and set aside;

[0047] (3) The third step, granulation and tableting: take the prepared premixed material mixed in the first step, granulate it with the binder solution, dry the whole granules, add magnesium stearate, mix well, and tablet press to obtain 20,000 ferrous succinate tablets.

[0048] Preparation Example 5

[0049] Ferrous succinate 20kg, filler calcium hydrogen phosphate dihydrate 13.2kg, disintegrant corn starch 10.8kg, succinic acid 20kg, binder povidone K30 3.5kg, lubricant magnesium stearate 0.68kg.

[0050] The above pharmaceutical composition is prepared into tablets, and the preparation method of the tablets is as follows:

[0051] (1) The first step is premixing: ferrous succinate, calcium hydrogen phosphate dihydrate, corn starch, and succinic acid are mixed uniformly to obtain a premixed material for use;

[0052] (2) The second step is to prepare the adhesive solution: take povidone K30 and add it to 60% ethanol; the weight ratio of povidone K30 to 60% ethanol is 7:8; mix well and set aside;

[0053] (3) The third step, granulation and tableting: take the prepared premixed material mixed in the first step, granulate it with the binder solution, dry the whole granules, add magnesium stearate, mix well, and tablet press to obtain 200,000 ferrous succinate tablets.

[0054] Comparative Example 1

[0055] 28.57 parts by weight of ferrous succinate, 33.86 parts by weight of calcium hydrogen phosphate dihydrate (D90<45m), 10 parts by weight of corn starch, 28.57 parts by weight of succinic acid, 1 part by weight of magnesium stearate and 2 parts by weight of povidone K30.

[0056] Preparation of ferrous succinate tablets: 95% ethanol is added to 2 parts of povidone K30 to adjust the mass percentage of povidone K30 to 25%, and then 28.57 parts of ferrous succinate, 10 parts of corn starch, 28.57 parts of succinic acid and 33.86 parts of calcium hydrogen phosphate dihydrate are added to a wet granulator for wet granulation. After granulation is completed, the mixture is dried. After drying, 1 part of magnesium stearate is added to the mixture and the mixture is compressed into tablets (plain tablets).

[0057] Comparative Example 2

[0058] 28.57 parts by weight of ferrous succinate, 26.86 parts by weight of calcium hydrogen phosphate dihydrate (D90<45m), 10 parts by weight of corn starch, 28.57 parts by weight of succinic acid, 1 part by weight of magnesium stearate and 5 parts by weight of povidone K30.

[0059] Preparation of ferrous succinate tablets: 28.57 parts of ferrous succinate, 5 parts of corn starch, 14.28 parts of succinic acid, 26.86 parts of calcium hydrogen phosphate dihydrate, and 5 parts of povidone were added to a wet granulator and wet granulated using a 50% aqueous ethanol solution. After granulation, the mixture was dried. The remaining 5 parts of corn starch, 1 part of magnesium stearate, and 14.28 parts of succinic acid were added, mixed, and compressed into plain tablets.

[0060] Comparative Example 3

[0061] Ferrous succinate tablets (plain tablets) were obtained according to the preparation method of Example 5 of CN117599004A specification.

[0062] Detection and analysis methods:

[0063] Take an appropriate amount of fine powder under the content determination item (approximately equivalent to 0.5g of ferrous succinate), accurately weigh it, put it in a 300ml iodine bottle, add 60ml of water and 30ml of 1mol / L sulfuric acid solution, dissolve it, add 0.25g of zinc powder, seal it, and let it stand at room temperature for 20 minutes. Filter it with a vertical frit funnel covered with a zinc powder layer, wash the filter layer with 10ml of dilute sulfuric acid solution and 10ml of water, combine the washing liquid and the filtrate, add 2 drops of o-phenanthroline indicator solution, titrate with cerium sulfate titrant (0.1mol / L), and correct the titration result with a blank test. Each 1ml of cerium sulfate titrant (0.1mol / L) is equivalent to 5.585mg of iron. The total iron content is subtracted from the ferrous iron (Fe 2+ ) content, namely high iron (Fe 3+ ) content. The iron content of each tablet shall not exceed 2.5% of the labeled amount.

[0064] The dissolution rate was determined according to the dissolution and release method (Method 2, Part 4, General Chapter 0931, Chinese Pharmacopoeia 2020 Edition).

[0065] The dissolution conditions were: 1000 ml of hydrochloric acid solution (9→1000) as the dissolution medium, a rotation speed of 75 revolutions per minute, and operation according to the law. Samples were taken after 90 minutes.

[0066] Take the eluate of the test solution and filter it, accurately measure 2 ml of the filtrate, place it in a 25 ml volumetric flask, add 2 ml of a mixed solution of o-phenanthroline and hydroxylamine hydrochloride (take 0.12 g of o-phenanthroline and 10 g of hydroxylamine hydrochloride, add 100 ml of water to dissolve), shake well, add 10 ml of 2 mol / L sodium acetate solution, dilute to the scale with water, shake well, and let it stand for 15 minutes.

[0067] Reference solution: Accurately measure the standard iron solution {accurately weigh 1.756g of ferrous ammonium sulfate [Fe(NH4)2(SO4)2·6H2O], place it in a 250ml volumetric flask, add a small amount of water to dissolve it, add 10ml of sulfuric acid, let it cool, dilute it to the scale with water, shake it well, accurately measure 1ml, place it in a 50ml volumetric flask, dilute it to the scale with water, shake it well, and you have 1ml equivalent to 20μg of Fe 2+}3ml, follow the method for the test solution, starting from "place in a 25ml measuring flask", and operate in the same way.

[0068] Determination method: Take the test solution and the reference solution, and measure the absorbance at a wavelength of 510 nm according to the UV-visible spectrophotometry method (General Chapter 0401 of Part IV of the Chinese Pharmacopoeia 2020 Edition), and calculate the dissolution amount of each tablet.

[0069] The limit of 80% of the labeled amount shall comply with the regulations.

[0070] Content determination: Take 20 tablets of this product, accurately weigh them, grind them into powder, accurately weigh an appropriate amount (equivalent to 0.5g of ferrous succinate), add a mixture of 20ml of dilute sulfuric acid and 30ml of water, shake to dissolve the ferrous succinate, add 2 drops of o-phenanthroline indicator solution, immediately titrate with cerium sulfate titrant (0.1mol / L), and correct the titration result with a blank test. Each 1ml of cerium sulfate titrant (0.1mol / L) is equivalent to 5.585mg of Fe 2+ . The content is not less than 32.6%.

[0071] Test method: Ferrous succinate tablets (plain tablets) obtained by the above different preparation methods were sampled according to the influencing factors. The test results are as follows:

[0072] Table 2 Comparison of the quality of different preparations at 50℃

[0073]

[0074] Table 3 Comparison of quality of preparations with different illumination

[0075]

[0076] Table 4 Comparison of the quality of different preparations at high humidity RH75%

[0077]

[0078] Conclusion: The above test shows that the preparation of the present invention has a high temperature, high humidity and light test, and the Fe 2+ The content changes little, the high Fe content meets the requirements of the quality standard, and the dissolution rate is not less than 90%; while the Fe content of Comparative Example 1 and Comparative Example 2 after high temperature, high humidity and light test 2+ The content, high Fe content and solubility all meet the requirements of the quality standards. After high temperature, high humidity and light tests, the solubility of Comparative Example 3 does not meet the requirements of the quality standards; this fully demonstrates that the preparation of the present invention has better quality.

[0079] The above embodiments are intended to illustrate the present invention only and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the embodiments, it should be understood by those skilled in the art that various combinations, modifications, or equivalent substitutions of the technical solutions of the present invention do not depart from the spirit and scope of the technical solutions of the present invention and should be encompassed by the scope of the claims of the present invention.

Claims

1. A pharmaceutical composition containing ferrous succinate, characterized in that The pharmaceutical composition comprises: ferrous succinate, a filler, a disintegrant, a binder and a lubricant.

2. A pharmaceutical composition containing ferrous succinate according to claim 1, wherein ferrous succinate is 95-105 parts by weight, filler is 60-70 parts by weight, disintegrant is 150-160 parts by weight, binder is 17-18 parts by weight, and lubricant is 3-4 parts by weight.

3. A pharmaceutical composition containing ferrous succinate according to claim 1 or 2, wherein ferrous succinate is 95-105 parts by weight, filler calcium hydrogen phosphate dihydrate is 60-70 parts by weight, disintegrants corn starch and succinic acid are 150-160 parts by weight in total (weight ratio 27:50), binder povidone K30 is 17-18 parts by weight, and lubricant magnesium stearate is 3-4 parts by weight; preferably ferrous succinate is 100 parts by weight, filler calcium hydrogen phosphate dihydrate is 66 parts by weight, disintegrant corn starch is 54 parts by weight, succinic acid is 100 parts by weight, binder povidone K30 is 17.5 parts by weight, and lubricant magnesium stearate is 3.4 parts by weight.

4. A pharmaceutical composition containing ferrous succinate according to claim 3, wherein the weight ratio of the disintegrant corn starch to succinic acid is 27:

50.

5. A pharmaceutical composition containing ferrous succinate according to claim 3, wherein the pharmaceutical composition is prepared into a solid preparation.

6. A pharmaceutical composition containing ferrous succinate according to claim 3, wherein the pharmaceutical composition is prepared into tablets, capsules or granules.

7. A pharmaceutical composition containing ferrous succinate according to claim 6, wherein the preparation method of the tablet is: (1) The first step is premixing: ferrous succinate, calcium hydrogen phosphate dihydrate, corn starch, and succinic acid are mixed uniformly to obtain a premixed material for use; (2) Step 2, preparation of adhesive solution: take povidone K30, add it to 60% ethanol, mix well, and set aside; (3) The third step, granulation and tableting: take the prepared premixed material mixed in the first step, granulate it with the binder solution, dry the whole granules, add magnesium stearate, mix well, and tablet press to obtain ferrous succinate tablets.

8. A pharmaceutical composition containing ferrous succinate according to claim 7, wherein the weight ratio of povidone K30 to 60% ethanol is 7:8.

Images