A pharmaceutical composition of sodium ferrous citrate and its preparation method

Abstract

The present invention provides a pharmaceutical composition of sodium ferrous citrate and a preparation method thereof, belonging to the field of medicine. The pharmaceutical composition of sodium ferrous citrate comprises the following components in mass percentage: 70-95% of sodium ferrous citrate, 1-30% of a filler, 1-10% of a binder, and 1-10% of a lubricant; the filler includes one or more of microcrystalline cellulose, calcium hydrogen carbonate, lactose, mannitol, calcium hydrogen phosphate, and corn starch. By adjusting the composition and proportion of the filler, binder, and lubricant, the present invention improves the properties of the product and the problem of sticking to the punch during the tabletting process, improves its texture performance, enhances the stability of divalent iron in the pharmaceutical composition, reduces the friability, improves the bioavailability, and the surface of the sodium ferrous citrate tablets remains smooth after long-term storage, having excellent stability.

Description

Technical Field

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

[0002] Sodium Ferrous Citrate, also known as ferrous citrate sodium, is a greenish-white to yellowish-green powder, odorless, with a faint iron taste, and its molecular formula is Na 4 FeC1 2 H 10 O 14 . It is a complex drug of sodium citrate and divalent iron used for oral administration to treat iron deficiency anemia. Iron is one of the important elements in the human body, participates in the synthesis of hemoglobin, and plays an important role in oxygen transport and 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 part of muscle cells that stores oxygen and provides 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 agents to 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, behavioral abnormalities, physical weakness, mucosal tissue changes, and skin and nail lesions, can also be gradually corrected. Iron agents are mainly absorbed in the descending part of the duodenum and the proximal jejunum in the form of ferrous ions (Fe 2+ ). Clinical results show that the hemoglobin returns to the normal value relatively quickly after taking sodium ferrous citrate. 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 emphasized and expanded. Sodium ferrous citrate is widely used in health products, nutritional products, and pharmaceuticals.

[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 the patent number WO2021137780A1 relates to a thin film tablet composition containing heme iron for treating iron deficiency while optimizing the characteristics of the film coating. The composition containing heme iron can be combined with one or more other iron sources (ionic iron and / or liposomal iron). The composition of the invention can include one or more forms of vitamins and / or minerals, in amounts and in any combination with the selected heme iron and / or the selected ionic iron salts and / or liposomal iron. The ionic iron is preferably in the form of a soluble iron salt, and the 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, iron triglycinate, ferrous diglycinate, ferric nitrate, ferrous saccharate, ferric sulfate, ferrous gluconate, sodium ferrous citrate, other pharmaceutically acceptable soluble iron salts, mixtures, mixtures and / or compositions thereof. In order to provide smooth tablets and solve the coating problem, a film coating using a combination of polyvinylpyrrolidone, synthetic polymers of polydextrose, and cellulose derivatives selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose, ethyl cellulose, and microcrystalline cellulose is used.

[0006] Sodium ferrous citrate is applied in pharmaceuticals and is mostly prepared into tablets. In sodium ferrous citrate tablets, the main drug accounts for a large proportion, and sticking to the punch is likely to occur during tabletting. The friability of the finished tablets is unqualified, and there are also depressions on the surface, which affect the preparation process of the product and the properties of the tablets. Using conventional binders for granulation and lubricants for mixing alone cannot improve the sticking problem during tabletting of the product. Sodium ferrous citrate tablets are a drug marketed in Japan and are not currently marketed in China. The indication is iron deficiency anemia. Its main components are sodium ferrous citrate, microcrystalline cellulose, calcium stearate, carboxymethyl cellulose, and hydroxypropyl cellulose. However, as an intermediate, the divalent iron in the tablets prepared therefrom will gradually oxidize to produce trivalent iron during storage, reducing the product quality, deteriorating iron absorption, and changing the properties, such as the color of the tablets turning yellow.

[0007] Based on the above problems, the present invention has improved the composition of sodium ferrous citrate to obtain a product with better tablet properties. 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 includes sodium ferrous citrate, fillers, binders, and lubricants. By adjusting the composition and proportion of the binders and lubricants, the properties of the product and the sticking problem during tabletting can be improved, its texture properties can be improved, the friability can be reduced, it has excellent dissolution, high tablet quality and bioavailability, the stability of divalent iron in the pharmaceutical composition can be improved, the color of the tablets can be prevented from turning yellow, and the surface of the sodium ferrous citrate tablets is still smooth after long-term storage, having excellent stability.

[0009] To achieve the above object, 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 components with the following mass percentages:

[0011]

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

[0013] The sodium ferrous citrate can be a commercially available material, which is not limited herein. 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 hydrogen carbonate, lactose, mannitol, calcium hydrogen phosphate, and corn starch. Preferably, the filler is microcrystalline cellulose and calcium hydrogen carbonate, and the mass ratio of microcrystalline cellulose to calcium hydrogen carbonate 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 serve as both a filler and a disintegrant at the same time. The microcrystalline cellulose is of the type commonly used by those skilled in the art and is not limited herein. The microcrystalline cellulose is in the form of rod-shaped or granular crystals. Due to the presence of hydrogen bonds between microcrystalline cellulose molecules, the hydrogen bonds associate under pressure, so it has high compressibility and molding effect. Depending on the production process and use, different types of microcrystalline cellulose can be used. Preferably, the microcrystalline cellulose is the 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 content of the filler in the ferrous sodium citrate pharmaceutical composition is 1 - 30%, preferably 1 - 20%. In one embodiment, the mass percentage content of the filler in the ferrous sodium citrate pharmaceutical composition is 5 - 30%. In one embodiment, the filler in the ferrous sodium citrate pharmaceutical composition is microcrystalline cellulose and calcium hydrogen carbonate, and the mass percentage content of the filler is 8%. In one embodiment, the filler is microcrystalline cellulose, and the mass percentage content of microcrystalline cellulose in the ferrous sodium citrate pharmaceutical composition is 6.6%. After being used for granulation, the microcrystalline cellulose can improve the fluidity of the pharmaceutical composition.

[0015] The binder includes one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, povidone, and starch paste. In one embodiment, the binder is a mixture of hydroxypropyl cellulose and hydroxypropyl methylcellulose. In one embodiment, the binder is a mixture of hydroxypropyl cellulose and hydroxypropyl methylcellulose, and the mass ratio of hydroxypropyl cellulose to hydroxypropyl methylcellulose in the mixture is 1 - 4:1, preferably 2:1. The mass ratio of the binder in the ferrous sodium citrate pharmaceutical composition is 1 - 10%, preferably 1 - 5%. In one embodiment, the mass ratio of the binder in the ferrous sodium citrate pharmaceutical composition is 3%. Preferably, the binder is a mixture of hydroxypropyl cellulose and hydroxypropyl methylcellulose; the mass ratio of hydroxypropyl cellulose to hydroxypropyl methylcellulose 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 to silicon dioxide in the mixture is 1-4:1-4, preferably 1:1. The silicon dioxide can be of the types commonly used in pharmaceutical excipients. Depending on 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 to 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 herein, including but not limited to tablets, granules, or capsules. Preferably, the dosage form of the pharmaceutical composition is a tablet, and the tablet can be an ordinary tablet, chewable tablet, dispersible tablet, or 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] Mix sodium ferrous citrate, a filler, and a binder to granulate, dry after granulation, add a lubricant, and press tablets to obtain the pharmaceutical composition of sodium ferrous citrate.

[0021] Specifically, the method for preparing the pharmaceutical composition comprises the following steps:

[0022] 1) Granulate ferrous citrate sodium, filler, and binder by wet granulation. The mass percentages of ferrous citrate sodium, filler, and binder are 70 - 95%, 1 - 30%, and 1 - 10% respectively; preferably, the filler is microcrystalline cellulose and calcium hydrogen carbonate, and the mass ratio of microcrystalline cellulose to calcium hydrogen carbonate is 1:2 - 4. The binder is a mixture of hydroxypropyl cellulose and hydroxypropyl methylcellulose, and the mass ratio of hydroxypropyl cellulose to hydroxypropyl methylcellulose is 1 - 4:1, preferably 2:1. The wet granulation uses a wetting agent, which is a mixture of water and ethanol. Preferably, the volume percentage of ethanol in the wetting agent is 5 - 40%.

[0023] 2) After wet granulation, perform drying. The instruments used for drying include but are not limited to fluidized bed dryers, convection dryers, box dryers, vibrating dryers, natural convection type constant temperature dryers, forced convection type constant temperature dryers, and forced convection type constant temperature and humidity dryers. Preferably, drying is performed using a fluidized bed. Control the moisture content to 1 - 2%, add a lubricant. The lubricant is preferably a composition of magnesium stearate and colloidal silica. The mass percentage of magnesium stearate in the lubricant is 25 - 75%, preferably 50%. Press and coat to obtain the pharmaceutical composition of ferrous citrate sodium.

[0024] Compared with the prior art, the present invention has the following beneficial effects: The pharmaceutical composition of ferrous citrate sodium provided by the present invention includes ferrous citrate sodium, filler, binder, and lubricant. By adjusting the composition and ratio of the filler, binder, and lubricant, a tablet product can be prepared, which can improve the stability of divalent iron in the pharmaceutical composition, prevent the tablets from turning yellow, improve the properties of the product and the sticking problem during the tabletting process, improve its texture performance, reduce the friability, have excellent dissolution, high tablet quality and bioavailability. The surface of the ferrous citrate sodium tablets remains smooth after long-term storage, and has excellent stability. Description of the Drawings

[0025] Figure 1 It is a tablet diagram of ferrous citrate sodium for Example 1;

[0026] Figure 2 It is a tablet diagram of ferrous citrate sodium for Comparative Example 1. Detailed Embodiments

[0027] It should be noted that, unless otherwise specified, the raw materials used in the present invention are all ordinary commercially available products, and no specific limitation is imposed on their sources.

[0028] The following raw material sources are for illustrative purposes:

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

[0030] Hydroxypropylcellulose: Ashland Specialty Ingredients, G.P EF;

[0031] Hydroxypropylmethylcellulose: Ashland Specialty Ingredients, G.P E5;

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

[0033] Colloidal silicon dioxide: Evonik Corporation.

[0034] Example 1

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

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

[0037]

[0038]

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

[0040] 1) Granulate sodium ferrous citrate, fillers (microcrystalline cellulose and calcium hydrogen carbonate), and binder (a mixture of hydroxypropylcellulose and hydroxypropylmethylcellulose) by wet granulation. 0.1 g of wetting agent is used for wet granulation. The wetting agent is a mixture of water and ethanol, and the volume percentage of ethanol in the wetting agent is 16.7%. The specific process conditions for wet granulation are:

[0041] Premix stirring at 125 rpm, shearing at 1000 rpm, mixing for 5 min, spraying pressure of 0.3 MPa, peristaltic pump speed of 7 Hz, stirring at 125 rpm, shearing at 1000 rpm, total liquid addition time of 10 min, and granulating for 1 min after liquid addition is completed.

[0042] 2) After wet granulation, use a fluidized bed for drying. The specific process conditions for fluidized bed drying are: inlet air temperature set at 65 °C, material temperature set at 40 °C, water content controlled at 2%, add lubricant (a composition of magnesium stearate and colloidal silicon dioxide), press tablets and coat them. The specific process flow for pressing tablets and coating is:

[0043] Tablet pressing: Use a high-speed rotary tablet press to press tablets, with an average hardness of 60 N and a tablet pressing speed of 50,000 / h;

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

[0045] Example 2

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

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

[0048]

[0049] Prepare sodium ferrous citrate tablets according to the preparation steps of Example 1.

[0050] Example 3

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

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

[0053]

[0054] Prepare sodium ferrous citrate tablets according to the preparation steps of Example 1.

[0055] Example 4

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

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

[0058]

[0059] Prepare sodium ferrous citrate tablets according to the preparation steps of Example 1.

[0060] Example 5

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

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

[0063]

[0064] Prepare sodium ferrous citrate tablets according to the preparation steps of Example 1.

[0065] Example 6

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

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

[0068]

[0069] Prepare sodium ferrous citrate tablets according to the preparation steps of Example 1.

[0070] Comparative Example 1

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

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

[0073]

[0074]

[0075] Prepare sodium ferrous citrate tablets according to the preparation steps of Example 1.

[0076] Comparative Example 2

[0077] The difference from Example 1 is that "calcium hydrogen carbonate" in Example 1 is replaced with "microcrystalline cellulose", and 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 with "hydroxypropyl methylcellulose", and 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 "magnesium stearate" in Example 5 is replaced with "colloidal silica", and 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 with "hydroxypropyl methylcellulose", and 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 ratio of microcrystalline cellulose is 1.6%, and the mass ratio of calcium hydrogen carbonate is 5.0%" in Example 1 is replaced with "the mass ratio of microcrystalline cellulose is 5.0%, and the mass ratio of calcium hydrogen carbonate is 1.6%", and other steps and operations are the same as those in Example 1 to obtain sodium ferrous citrate tablets.

[0086] Test Example

[0087] The following performance tests were carried out using Examples 1-6, Comparative Examples 1-6 and the commercial drug (the original Ferromia sodium ferrous citrate tablets of Nippon Shokubai Co., Ltd., product number: 007329-001):

[0088] 1. Measure 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 Figure 1 and Figure 2 shown. Figure 1 Figure of the sodium ferrous citrate tablet of Example 1 Figure 2 Figure of the sodium ferrous citrate tablet of Comparative Example 1 Figures 1-2 The results show that the sodium ferrous citrate tablets of Example 1 have better effects and the tablet surfaces are smooth. The surfaces of the sodium ferrous citrate tablets of the comparative examples have depressions, small pits, etc. to varying degrees, the surfaces are rough, and the appearance is poor.

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

[0091] According to the provisions of the Pharmacopoeia 0923 Friability Test for Tablets, the friability of the sodium ferrous citrate tablets was examined.

[0092] The results are shown in Table 8.

[0093] Table 8 Friability of the 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 excellent friability, among which the friability of the sodium ferrous citrate tablets of Example 1 is the lowest.

[0096] Compared with the sodium ferrous citrate tablets prepared in Example 1 and Comparative Examples 1-2 of the present invention, after six friability tests, the friability of Example 1 is highly stable and lower than that of Comparative Example 1. Therefore, the sodium ferrous citrate tablets of Example 1 of the present invention have better anti-wear and vibration resistance than Comparative Example 1 and have better product quality. The results show that the lubricants are magnesium stearate and colloidal silicon dioxide, and the two work synergistically to reduce the friability of the sodium ferrous citrate tablets.

[0097] Comparing Example 4 with Comparative Example 3, after six friability tests, it was found that the friability of the sodium ferrous citrate tablets in Example 4 was significantly lower than that in Comparative Example 3. The results showed that when the binders were hypromellose and hydroxypropyl methylcellulose, they had a synergistic effect and could reduce 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 in Example 5 was significantly lower than that in Comparative Example 4. The results showed that when the lubricant was only colloidal silicon dioxide, the friability of the sodium ferrous citrate tablets increased significantly.

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

[0100] 3. Determine the dissolution rates of the sodium ferrous citrate tablets of Examples 1-6, Comparative Examples 1-6, and the commercial drug

[0101] Table 9 Dissolution rates of the sodium ferrous citrate tablets

[0102]

[0103] The results in Table 9 showed that the sodium ferrous citrate tablets in the examples of the present invention had significantly excellent dissolution rates, high tablet quality and 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 rate tests, the dissolution rate of Example 1 was not much different from that of Comparative Example 1.

[0105] Comparing Example 4 with Comparative Example 3, after six dissolution rate tests, it was found that the dissolution rate of the sodium ferrous citrate tablets in Example 4 was significantly higher than that in Comparative Example 3. The results showed that when the binders were hypromellose and hydroxypropyl methylcellulose, they had a synergistic effect and could increase the dissolution rate of the sodium ferrous citrate tablets.

[0106] Comparing Example 6 with Comparative Example 5, after six dissolution rate tests, it was found that the dissolution rate of the sodium ferrous citrate tablets in Example 6 was significantly higher than that in Comparative Example 5. The results showed that when the binder was only hydroxypropyl methylcellulose, the dissolution rate of the sodium ferrous citrate tablets decreased significantly.

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

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

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

[0110] Table 10 Ferric iron content in sodium ferrous citrate tablets

[0111]

[0112] The results in Table 10 show that adding calcium bicarbonate to the sodium ferrous citrate tablets of the present invention synergistically enhances the effect with microcrystalline cellulose, and has an obvious effect of reducing the ferric iron content of the product. When calcium bicarbonate and microcrystalline cellulose maintain a certain ratio (mass ratio 1:2 - 4), the effect of preventing the oxidation of ferrous iron 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 that of 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 a limitation on the protection scope of the present invention. Any simple modification or equivalent replacement of the technical solution of the present invention by those of ordinary skill in the art shall not depart 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: The formula of the pharmaceutical composition is as follows: The preparation steps of the ferrous citrate pharmaceutical composition are specifically as follows: 1) A mixture of sodium ferrous citrate, microcrystalline cellulose, calcium bicarbonate, hydroxypropyl cellulose and hydroxypropyl methylcellulose is granulated by wet granulation. The wet granulation uses 0.1 g of a wetting agent, which is a mixture of water and ethanol. The volume proportion of ethanol in the wetting agent is 16.7%. The specific process conditions of the wet granulation are: Premixing stirring 125rpm, shearing 1000rpm, mixing 5min, spraying pressure 0.3MPa, peristaltic pump speed 7Hz, stirring 125rpm, shearing 1000rpm, total liquid addition time 10min, granulation 1min after liquid addition; 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 content is controlled to be 2%, a composition of magnesium stearate and colloidal silicon dioxide is added, tableting and coating are performed, and the specific process flow of tableting and coating is as follows: Tablet pressing: Use high-speed rotary tablet press, average hardness 60N, tablet pressing speed 5w / h; 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.

2. A pharmaceutical composition of sodium ferrous citrate, characterized in that: The formula of the pharmaceutical composition is as follows:

3. A pharmaceutical composition of sodium ferrous citrate, characterized in that: The formula of the pharmaceutical composition is as follows:

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