Pharmaceutical composition of sodium ferrous citrate and preparation method thereof

Abstract

The invention provides a pharmaceutical composition of sodium ferrous citrate and a preparation method of the pharmaceutical composition, and belongs to the field of medicines. The pharmaceutical composition of the sodium ferrous citrate comprises the following components in percentage by mass: 70-95% of the sodium ferrous citrate, 1-30% of a filling agent, 1-10% of an adhesive and 1-10% of a lubricating agent, the filling agent comprises one or more of microcrystalline cellulose, calcium bicarbonate, lactose, mannitol, calcium hydrophosphate and corn starch. By adjusting the composition and proportion of the filling agent, the adhesive and the lubricant, the character of the product is improved, the sticking problem in the tabletting process is solved, the texture performance of the product is improved, the stability of ferrous iron in the pharmaceutical composition is improved, the friability is reduced, the bioavailability is improved, and the sodium ferrous citrate tablet is still smooth in surface after being stored for a long time, and has a good application prospect. The stability is excellent.

Description

Technical Field

[0001] The invention belongs to the field of medicine and relates to a sodium ferrous citrate pharmaceutical composition, and specifically relates to a sodium ferrous citrate pharmaceutical composition and a preparation method thereof. Background Art

[0002] Sodium Ferrous Citrate, also known as sodium ferrous citrate, is a greenish white to yellowish green powder, odorless, with a faint iron taste, and its molecular formula is Na4FeC12H 10 O 14 . It is a complex drug of sodium citrate and divalent iron for oral administration to treat iron deficiency anemia. Iron is one of the important elements of the human body. It participates in the synthesis of hemoglobin and plays an important role in transferring oxygen and participating in human metabolic activities. Iron is the main component of hemoglobin and myoglobin. Hemoglobin is the main carrier of oxygen in red blood cells, and myoglobin is the site of oxygen storage in muscle cells, providing oxygen for muscle movement. Most enzymes and factors related to the tricarboxylic acid cycle contain iron, or can only function in the presence of iron. Therefore, after actively supplementing iron for iron-deficient patients, in addition to accelerating hemoglobin synthesis, symptoms related to tissue iron deficiency and reduced iron-containing enzyme activity, such as growth retardation, abnormal behavior, lack of physical strength, changes in mucosal tissues, and skin and nail lesions can also be gradually corrected. Iron supplements are mainly ferrous ions (Fe 2+ ) form is absorbed in the descending part of the duodenum and the proximal part of the jejunum. Clinical results show that after taking sodium ferrous citrate, the hemoglobin returns to normal values ​​quickly. In recent years, people's understanding of the physiological and pharmacological effects of iron salts has gradually deepened, and the application of iron salts has been increasingly valued and expanded. Sodium ferrous citrate is widely used in health products, nutritional products and medicines.

[0003] The invention patent with publication number CN117694527A discloses a suspension mineral oral liquid and a preparation method thereof, wherein the suspension mineral oral liquid comprises the following components by weight: 0.02-0.06 parts of gellan gum, 9-12 parts of xanthan gum, 80-120 parts of sugar alcohol and 90-150 parts of nutrient supplements, wherein the solvent of the suspension mineral oral liquid is water; wherein xanthan gum: gellan gum = 1:0.002-1:0.005. The nutrient supplement comprises an iron supplement, and the iron supplement comprises at least one of food-grade ferrous gluconate, ferrous fumarate, ferrous sulfate, ferrous lactate, ferrous succinate, ferric pyrophosphate, ferric citrate and sodium ferrous citrate. By adding gellan gum, xanthan gum, etc. in an optimal ratio and using high-pressure homogenization technology to change the state of the oral liquid from a flowing liquid to a suspended fluid, it is possible to design oral liquids with higher mineral content, solve the problem of soluble solids precipitation and precipitation in a variety of mineral oral liquids, and optimize the product in appearance and taste.

[0004] The invention patent with publication number CN117179113A discloses a kind of iron-rich composite juice gel soft candy product and its preparation method, and the soft candy product mainly includes the following components according to weight: 70-90 parts of sugar alcohol, 2-8 parts of gelling agent, 10-15 parts of purified water, 0.5-2 parts of iron nutrition enhancer, 2-4 parts of fruit juice, 0.2-0.6 parts of edible flavor, 0.2-0.6 parts of acidity regulator, and 0.1-0.2 parts of anti-sticking oil. The iron nutrition enhancer is composed of one or more combinations of sodium ferric ethylenediaminetetraacetate, ferric pyrophosphate, heme iron, sodium ferrous citrate, and ferrous gluconate. The present invention adopts sodium ferric ethylenediaminetetraacetate, ferric pyrophosphate, and heme iron as iron nutrition enhancers. These iron nutrition enhancers have no iron smell, stable properties, high absorption rate, good absorbability, high bioavailability, and good iron supplementation effect. At the same time, xylitol, maltitol, isomalt, sorbitol, mannitol and natural concentrated fruit juice are used, which has a strong fruity aroma, a sweet and glutinous taste, rich elasticity and low sugar content.

[0005] The international patent with patent number WO2021137780A1 relates to a film tablet composition comprising heme iron, which is used to treat iron deficiency and optimize film coating properties. The composition comprising heme iron can be combined with one or more other iron sources (ionic iron and / or liposomal iron). The composition of the invention may include one or more forms of vitamins and / or minerals, any combination of their quantity and selected heme iron and / or selected ionic iron salts and / or liposomal iron. Ionic iron is preferably in the form of soluble iron salts, and soluble iron salts include but are not limited to ferrous sulfate, ferrous gluconate, ferrous fumarate, ferrous hydrogen phosphite, albumin iron, ferric chloride, ferric citrate, ammonium ferric citrate, ferrous chloride, ferrous iodide, ferrous lactate, triglycine iron, diglycine ferrous, ferrous nitrate, ferrous sucrose acid, ferrous sulfate, ferrous gluconate, ferrous sodium citrate, other pharmaceutically acceptable solubility iron salts, mixtures thereof, mixtures and / or compositions. In order to provide smooth tablets and solve the coating problem, a film coating of a combination of povidone, a polydextrose type synthetic polymer and a cellulose derivative selected from hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylcellulose and microcrystalline cellulose is used.

[0006] Sodium ferrous citrate is used in pharmaceutical preparations, and is mostly prepared as tablets. The main drug accounts for a large proportion of sodium ferrous citrate tablets, and sticking is prone to occur during tableting. The brittleness of the finished tablets is unqualified, and there are depressions on the surface, which affects the product preparation process and the properties of the tablets. The use of conventional adhesive granulation and lubricant mixing alone cannot improve the tableting sticking problem of the product. Sodium ferrous citrate tablets are a drug listed in Japan. It is not currently listed in China and is indicated for iron deficiency anemia. Its main ingredients are sodium ferrous citrate, microcrystalline cellulose, calcium stearate, carboxymethyl cellulose, and hydroxypropyl cellulose. However, as an intermediate, the divalent iron in the tablets produced therefrom will gradually oxidize to produce trivalent iron during storage, reducing product quality, worsening iron absorption, and changing properties, such as yellowing of the tablet color.

[0007] Based on the above problems, the present invention improves the composition of sodium ferrous citrate to obtain a product with better tablet performance. Summary of the invention

[0008] The present invention aims at the problems existing in the prior art and provides a pharmaceutical composition of sodium ferrous citrate and a preparation method thereof. The pharmaceutical composition of sodium ferrous citrate provided by the present invention comprises sodium ferrous citrate, a filler, a binder and a lubricant. By adjusting the composition and ratio of the binder and the lubricant, the properties of the product and the sticking problem in the tableting process can be improved, the texture performance can be improved, the friability can be reduced, the dissolution is excellent, the tablet quality and bioavailability are high, the stability of divalent iron in the pharmaceutical composition is improved, the color of the tablet is prevented from turning yellow, and the surface of the sodium ferrous citrate tablet is still smooth after long-term storage, and the tablet has excellent stability.

[0009] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0010] In a first aspect, the present invention provides a pharmaceutical composition of sodium ferrous citrate, comprising the following components in percentage by weight:

[0011]

[0012] The filler includes one or more of microcrystalline cellulose, calcium bicarbonate, lactose, mannitol, calcium hydrogen phosphate and corn starch.

[0013] The sodium ferrous citrate is a commercially available material, which is not limited here. In one embodiment, the mass percentage of sodium ferrous citrate in the pharmaceutical composition of sodium ferrous citrate is 70-95%, preferably 70-90%. In one embodiment, the mass percentage of sodium ferrous citrate in the pharmaceutical composition of sodium ferrous citrate is 88.9%. In one embodiment, the mass percentage of sodium ferrous citrate in the pharmaceutical composition of sodium ferrous citrate is 90%. In one embodiment, the mass percentage of sodium ferrous citrate in the pharmaceutical composition of sodium ferrous citrate is 70%.

[0014] The filler includes one or more of microcrystalline cellulose, calcium bicarbonate, lactose, mannitol, calcium hydrogen phosphate and corn starch. Preferably, the filler is microcrystalline cellulose and calcium bicarbonate, and the mass ratio of the microcrystalline cellulose and calcium bicarbonate is 1:2-4, preferably 1:2.5-3.5, and more preferably 1:3.125. In one embodiment, the filler is microcrystalline cellulose, and the microcrystalline cellulose can also be used as a filler and a disintegrant at the same time. The microcrystalline cellulose is a type commonly used by those skilled in the art, and is not limited here. The microcrystalline cellulose is a rod-shaped or granular crystal. Since there are hydrogen bonds between microcrystalline cellulose molecules, hydrogen bonds are associated when compressed, so it has a high degree of compressibility and molding effect. According to the production process and use, different types of microcrystalline cellulose can be used. Preferably, the microcrystalline cellulose is microcrystalline cellulose suitable for wet granulation, including but not limited to one or more of PH101, MCC-CG, MCC-101, Avicel PH101, Avicel PH301 and UF711. The mass percentage of the filler in the pharmaceutical composition of sodium ferrous citrate is 1-30%, preferably 1-20. In one embodiment, the mass percentage of the filler in the pharmaceutical composition of sodium ferrous citrate is 5-30%. In one embodiment, the filler in the pharmaceutical composition of sodium ferrous citrate is microcrystalline cellulose and calcium bicarbonate, and the mass percentage of the filler is 8%. In one embodiment, the filler is microcrystalline cellulose, and the mass percentage of microcrystalline cellulose in the pharmaceutical composition of sodium ferrous citrate is 6.6%. After the microcrystalline cellulose is used for granulation, the fluidity of the pharmaceutical composition can be improved.

[0015] The binder includes one or more of hydroxypropyl cellulose, hypromellose, povidone and starch slurry. In one embodiment, the binder is a mixture of hydroxypropyl cellulose and hypromellose. In one embodiment, the binder is a mixture of hydroxypropyl cellulose and hypromellose, and the mass ratio of hydroxypropyl cellulose and hypromellose in the mixture is 1-4:1, preferably 2:1. The mass ratio of the binder in the pharmaceutical composition of sodium ferrous citrate is 1-10%, preferably 1-5%. In one embodiment, the mass ratio of the binder in the pharmaceutical composition of sodium ferrous citrate is 3%, preferably, the binder is a mixture of hydroxypropyl cellulose and hypromellose; the mass ratio of hydroxypropyl cellulose and hypromellose in the mixture is 2:1.

[0016] The lubricant includes one or more of magnesium stearate, calcium stearate and silicon dioxide, preferably a mixture of magnesium stearate and silicon dioxide. In one embodiment, the mass ratio of magnesium stearate and silicon dioxide in the mixture is 1-4:1-4, preferably 1:1. The silicon dioxide can be a type of silicon dioxide commonly used in pharmaceutical excipients. According to different production processes and uses, silicon dioxide includes but is not limited to colloidal silicon dioxide, precipitated silicon dioxide, light silicon dioxide, ultrafine silicon dioxide and hydrophobic silicon dioxide. In one embodiment, the silicon dioxide is colloidal silicon dioxide. The colloidal silicon dioxide has a high specific surface area, good fluidity and strong adsorption capacity. The mass ratio of the lubricant in the pharmaceutical composition of sodium ferrous citrate is 1-10%, preferably 1-5%. In one embodiment, the mass ratio of the lubricant in the pharmaceutical composition of sodium ferrous citrate is 1.5%, preferably, the lubricant is a mixture of magnesium stearate and colloidal silicon dioxide, and the mass ratio of magnesium stearate and colloidal silicon dioxide in the mixture is 1:1.

[0017] In the pharmaceutical composition, the mass ratio of the binder to the lubricant is 1-10:1-10, preferably 1-5:1-5. In one embodiment, the mass ratio of the binder to the lubricant is 3:1.5.

[0018] The dosage form of the pharmaceutical composition can be any common dosage form in the art, which is not limited here, including but not limited to tablets, granules or capsules. Preferably, the dosage form of the pharmaceutical composition is a tablet, which can be a regular tablet, a chewable tablet, a dispersible tablet, or a sustained-release tablet.

[0019] In a second aspect, the present invention provides a method for preparing the pharmaceutical composition according to the above technical solution, comprising the following steps:

[0020] The sodium ferrous citrate, filler and binder are mixed and granulated, dried after granulation, lubricant is added, and tableting is performed to obtain the sodium ferrous citrate pharmaceutical composition.

[0021] Specifically, the preparation method of the pharmaceutical composition comprises the following steps:

[0022] 1) Sodium ferrous citrate, a filler and a binder are granulated by wet granulation, wherein the mass percentages of the sodium ferrous citrate, the filler and the binder are 70-95%, 1-30% and 1-10% respectively; preferably, the filler is microcrystalline cellulose and calcium bicarbonate, the mass ratio of the microcrystalline cellulose and calcium bicarbonate is 1:2-4, the binder is a mixture of hydroxypropyl cellulose and hypromellose, the mass ratio of the hydroxypropyl cellulose and the hypromellose is 1-4:1, preferably 2:1; the wet granulation adopts a wetting agent, the wetting agent is a mixture of water and ethanol, preferably, the volume proportion of ethanol in the wetting agent is 5-40%;

[0023] 2) Drying after wet granulation, wherein the apparatus used for drying includes but is not limited to a fluidized bed dryer, a convection dryer, a box dryer, a vibration dryer, a natural convection constant temperature dryer, a forced convection constant temperature dryer and a forced convection constant temperature and humidity dryer, preferably a fluidized bed is used for drying; the moisture content is controlled to be 1-2% during drying, a lubricant is added, and the lubricant is preferably a composition of magnesium stearate and colloidal silicon dioxide, wherein the mass proportion of magnesium stearate in the lubricant is 25-75%, preferably 50%; tableting and coating are performed to obtain a pharmaceutical composition of sodium ferrous citrate.

[0024] Compared with the prior art, the present invention has the following beneficial effects: the pharmaceutical composition of sodium ferrous citrate provided by the present invention comprises sodium ferrous citrate, a filler, a binder and a lubricant, and the composition and proportion of the filler, the binder and the lubricant are adjusted at the same time to prepare a tablet product, which can improve the stability of divalent iron in the pharmaceutical composition, prevent the color of the tablet from turning yellow, improve the properties of the product and the sticking problem in the tableting process, improve its texture performance, reduce friability, have excellent dissolution, and have high tablet quality and bioavailability. The surface of the sodium ferrous citrate tablet is still smooth after long-term storage and has excellent stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a picture of the sodium ferrous citrate tablet of Example 1;

[0026] Figure 2 This is a picture of the sodium ferrous citrate tablet of Comparative Example 1. DETAILED DESCRIPTION

[0027] It is worth noting that, unless otherwise specified, the raw materials used in the present invention are all common commercially available products, and their sources are not specifically limited.

[0028] The following sources of raw materials are provided for illustrative purposes:

[0029] Microcrystalline cellulose: Jiangsu Xidian Pharmaceutical Excipients Co., Ltd., PH101;

[0030] Hydroxypropylcellulose: Ashland Specialty Ingredients, GP EF;

[0031] Hydroxypropyl methylcellulose: Ashland Specialty Ingredients, GP E5;

[0032] Magnesium stearate: Anhui Shanhe Pharmaceutical Excipients Co., Ltd.

[0033] Colloidal silica: Evonik Corporation.

[0034] Example 1

[0035] The specific formula of sodium ferrous citrate tablets is shown in Table 1.

[0036] Table 1 Specific formula of sodium ferrous citrate tablets of Example 1

[0037]

[0038]

[0039] The preparation steps of sodium ferrous citrate tablets are specifically as follows:

[0040] 1) Sodium ferrous citrate, filler (microcrystalline cellulose and calcium bicarbonate) and binder (mixture of hydroxypropyl cellulose and hydroxypropyl methylcellulose) are granulated by wet granulation, and 0.1 g of wetting agent is used for wet granulation, and the wetting agent is a mixture of water and ethanol, and the volume proportion of ethanol in the wetting agent is 16.7%. The specific process conditions of wet granulation are:

[0041] The premix was stirred at 125 rpm, sheared at 1000 rpm, mixed for 5 min, the spray pressure was 0.3 MPa, the peristaltic pump speed was 7 Hz, stirred at 125 rpm, sheared at 1000 rpm, the total liquid addition time was 10 min, and granulated for 1 min after the liquid addition was completed.

[0042] 2) After wet granulation, a fluidized bed is used for drying. The specific process conditions of the fluidized bed drying are: the air inlet temperature is set at 65°C, the material temperature is set at 40°C, the moisture is controlled to be 2%, a lubricant (a composition of magnesium stearate and colloidal silicon dioxide) is added, and the tablets are compressed and coated. The specific process flow of the tablet compression and coating is as follows:

[0043] Tablet pressing: Use high-speed rotary tablet press, average hardness 60N, tablet pressing speed 5w / h;

[0044] Coating: The inlet air temperature is 70°C, the pot speed is 7rpm, the atomization pressure is 0.2MPa, the fan pressure is 0.2MPa, the peristaltic pump speed is 20rpm, the tablet temperature is 40°C, the weight gain is 3%, and sodium ferrous citrate tablets are obtained.

[0045] Example 2

[0046] The specific formula of sodium ferrous citrate tablets is shown in Table 2.

[0047] Table 2 Specific formula of sodium ferrous citrate tablets of Example 2

[0048]

[0049] Sodium ferrous citrate tablets were prepared according to the preparation steps of Example 1.

[0050] Example 3

[0051] The specific formula of sodium ferrous citrate tablets is shown in Table 3.

[0052] Table 3 Specific formula of sodium ferrous citrate tablets of Example 3

[0053]

[0054] Sodium ferrous citrate tablets were prepared according to the preparation steps of Example 1.

[0055] Example 4

[0056] The specific formula of sodium ferrous citrate tablets is shown in Table 4.

[0057] Table 4 Specific formula of sodium ferrous citrate tablets of Example 4

[0058]

[0059] Sodium ferrous citrate tablets were prepared according to the preparation steps of Example 1.

[0060] Example 5

[0061] The specific formula of sodium ferrous citrate tablets is shown in Table 5.

[0062] Table 5 Specific formula of sodium ferrous citrate tablets of Example 5

[0063]

[0064] Sodium ferrous citrate tablets were prepared according to the preparation steps of Example 1.

[0065] Example 6

[0066] The specific formula of sodium ferrous citrate tablets is shown in Table 6.

[0067] Table 6 Specific formula of sodium ferrous citrate tablets of Example 6

[0068]

[0069] Sodium ferrous citrate tablets were prepared according to the preparation steps of Example 1.

[0070] Comparative Example 1

[0071] The specific formula of sodium ferrous citrate tablets is shown in Table 7.

[0072] Table 7 Comparative Example 1 Specific formula of sodium ferrous citrate tablets

[0073]

[0074]

[0075] Sodium ferrous citrate tablets were prepared according to the preparation steps of Example 1.

[0076] Comparative Example 2

[0077] The difference from Example 1 is that the "calcium bicarbonate" in Example 1 is replaced by "microcrystalline cellulose", and the other steps and operations are the same as those in Example 1 to obtain sodium ferrous citrate tablets.

[0078] Comparative Example 3

[0079] The difference from Example 4 is that "hydroxypropyl cellulose" in Example 4 is replaced by "hydroxypropyl methylcellulose", and the other steps and operations are the same as those in Example 4 to obtain sodium ferrous citrate tablets.

[0080] Comparative Example 4

[0081] The difference from Example 5 is that the "magnesium stearate" in Example 5 is replaced by "colloidal silicon dioxide", and the other steps and operations are the same as those in Example 5 to obtain sodium ferrous citrate tablets.

[0082] Comparative Example 5

[0083] The difference from Example 6 is that "hydroxypropyl cellulose" in Example 6 is replaced by "hydroxypropyl methylcellulose", and the other steps and operations are the same as those in Example 1 to obtain sodium ferrous citrate tablets.

[0084] Comparative Example 6

[0085] The difference from Example 1 is that: the "mass proportion of microcrystalline cellulose is 1.6%, and the mass proportion of calcium bicarbonate is 5.0%" in Example 1 is replaced by "the mass proportion of microcrystalline cellulose is 5.0%, and the mass proportion of calcium bicarbonate is 1.6%", and the other steps and operations are the same as in Example 1 to obtain sodium ferrous citrate tablets.

[0086] Test example

[0087] The following performance tests were performed using Examples 1-6, Comparative Examples 1-6 and a commercial drug (Ferromia Sodium Ferrous Citrate Tablets, an original drug of Japan Co., Ltd., product number: 007329-001):

[0088] 1. Determination of the flatness (smoothness) of the sodium ferrous citrate tablets of Example 1 and Comparative Example 1

[0089] The sodium ferrous citrate tablets of Example 1 and Comparative Example 1 are respectively as follows Figure 1 and Figure 2 As shown, Figure 1 This is a picture of the sodium ferrous citrate tablet of Example 1. Figure 2 This is a picture of the sodium ferrous citrate tablet of Comparative Example 1. Figure 1-2 The results show that the sodium ferrous citrate tablets of Example 1 have better effects and smooth tablet surfaces. The sodium ferrous citrate tablets of the comparative example have depressions and small pits to varying degrees on their surfaces, and have rough surfaces and poor appearance.

[0090] 2. Determination of the friability of sodium ferrous citrate tablets of Examples 1-6, Comparative Examples 1-6 and commercial medicines

[0091] The friability of sodium ferrous citrate tablets was tested according to the method specified in Pharmacopoeia 0923 Tablet Friability Test Method.

[0092] The results are shown in Table 8.

[0093] Table 8 Friability of sodium ferrous citrate tablets

[0094]

[0095] The results in Table 8 show that the sodium ferrous citrate tablets in the examples of the present invention have significantly superior friability, among which the sodium ferrous citrate tablets in Example 1 have the lowest friability.

[0096] Compared with the sodium ferrous citrate tablets prepared in Example 1 of the present invention and Comparative Examples 1-2, after six friability tests, the friability stability of Example 1 is high and lower than that of Comparative Example 1. Therefore, the sodium ferrous citrate tablets of Example 1 of the present invention have better wear and vibration resistance than Comparative Example 1 and have better product quality. The results show that the lubricant uses magnesium stearate and colloidal silicon dioxide, which synergistically enhance the friability of the sodium ferrous citrate tablets.

[0097] Example 4 was compared with Comparative Example 3. After six friability tests, it was found that the friability of the sodium ferrous citrate tablets of Example 4 was significantly lower than that of Comparative Example 3. The results showed that the binders used hydroxypropyl cellulose and hydroxypropyl methylcellulose, which synergistically enhanced the friability of the sodium ferrous citrate tablets.

[0098] Comparing Example 5 with Comparative Example 4, after six friability tests, it was found that the friability of the sodium ferrous citrate tablets of Example 5 was significantly lower than that of Comparative Example 4. The results showed that when only colloidal silicon dioxide was used as the lubricant, the friability of the sodium ferrous citrate tablets was significantly improved.

[0099] Comparing Example 6 with Comparative Example 5, after six friability tests, it was found that the friability of the sodium ferrous citrate tablets of Example 6 was significantly lower than that of Comparative Example 5. The results showed that when only hypromellose was used as the binder, the friability of the sodium ferrous citrate tablets was significantly improved.

[0100] 3. Determination of the dissolution rate of sodium ferrous citrate tablets of Examples 1-6, Comparative Examples 1-6 and commercial medicines

[0101] Table 9 Dissolution of sodium ferrous citrate tablets

[0102]

[0103] The results in Table 9 show that the sodium ferrous citrate tablets in the examples of the present invention have significantly excellent dissolution, high tablet quality and high bioavailability.

[0104] Compared with the sodium ferrous citrate tablets prepared in Example 1 of the present invention and Comparative Examples 1-2, after six dissolution tests, the dissolution of Example 1 was not much different from that of Comparative Example 1.

[0105] Comparing Example 4 with Comparative Example 3, after six dissolution tests, it was found that the dissolution of the sodium ferrous citrate tablets of Example 4 was significantly higher than that of Comparative Example 3. The results showed that the binders used hydroxypropyl cellulose and hydroxypropyl methylcellulose, which synergistically enhanced the dissolution of the sodium ferrous citrate tablets.

[0106] Comparing Example 6 with Comparative Example 5, after six dissolution tests, it was found that the dissolution of the sodium ferrous citrate tablets of Example 6 was significantly higher than that of Comparative Example 5. The results showed that when only hypromellose was used as the binder, the dissolution of the sodium ferrous citrate tablets was significantly reduced.

[0107] 4. Determination of the ferric iron content of sodium ferrous citrate tablets of Examples 1-6, Comparative Examples 1-6 and commercial medicines

[0108] Test method: Total iron (UV) - ferrous iron (titration)

[0109] The test results are shown in Table 10.

[0110] Table 10 Trivalent iron content of sodium ferrous citrate tablets

[0111]

[0112] The results in Table 10 show that the addition of calcium bicarbonate to the sodium ferrous citrate tablets of the present invention synergizes with microcrystalline cellulose to significantly reduce the ferric iron content of the product. When calcium bicarbonate and microcrystalline cellulose are kept in a certain ratio (mass ratio of 1:2-4), the effect of preventing ferrous iron from being oxidized is significantly better than that of the mass ratio of 2-4:1. Among them, the ferric iron content in the sodium ferrous citrate tablets of Example 1 is the lowest, which is better than the current commercial drugs.

[0113] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A pharmaceutical composition of sodium ferrous citrate, characterized in that: Includes the following components in percentage by mass: The filler includes one or more of microcrystalline cellulose, calcium bicarbonate, lactose, mannitol, calcium hydrogen phosphate and corn starch.

2. The pharmaceutical composition according to claim 1, characterized in that The fillers are microcrystalline cellulose and calcium bicarbonate.

3. The pharmaceutical composition according to claim 1, characterized in that The mass percentage of the filler is 1-20%.

4. The pharmaceutical composition according to claim 2, characterized in that: The mass ratio of the microcrystalline cellulose to calcium bicarbonate is 1:2-4.

5. The pharmaceutical composition according to claim 1, characterized in that: The binder includes one or more of hydroxypropyl cellulose, hydroxypropyl methyl cellulose, povidone and starch slurry.

6. The pharmaceutical composition according to claim 5, characterized in that The adhesive is a mixture of hydroxypropyl cellulose and hydroxypropyl methyl cellulose; the mass ratio of hydroxypropyl cellulose to hydroxypropyl methyl cellulose in the mixture is 1-4:

1.

7. The pharmaceutical composition according to claim 1, characterized in that: The lubricant includes one or more of magnesium stearate, calcium stearate and silicon dioxide.

8. The pharmaceutical composition according to claim 7, characterized in that: The lubricant is a mixture of magnesium stearate and silicon dioxide; the mass ratio of magnesium stearate to silicon dioxide in the mixture is 1-4:1-4; and the silicon dioxide is colloidal silicon dioxide.

9. The pharmaceutical composition according to any one of claims 1 to 8, characterized in that The dosage form of the pharmaceutical composition is tablet, granule or capsule.

10. The method for preparing the pharmaceutical composition according to any one of claims 1 to 9, characterized in that: The following steps are involved: The sodium ferrous citrate, the filler and the binder are mixed and granulated, the granulation is dried, a lubricant is added, and the tablets are pressed to obtain the sodium ferrous citrate pharmaceutical composition.

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