A kind of aluminum carbonate double-layer sheet and preparation method thereof

Abstract

A magnesium aluminum carbonate double-layer tablet is obtained by pressing a magnesium aluminum carbonate common layer and a magnesium aluminum carbonate sustained-release layer, wherein the magnesium aluminum carbonate common layer contains magnesium aluminum carbonate as a main drug, and the auxiliary materials are a filler and a disintegrant, and the magnesium aluminum carbonate sustained-release layer contains magnesium aluminum carbonate as a main drug, and the auxiliary materials are a drug administration rate regulator, a gastric floating additive, a swelling agent, a foaming agent, and a hydrophilic gel. The magnesium aluminum carbonate double-layer tablet prepared by the present invention has a stable performance within 24 months, and the main drug content of the common layer and the sustained-release layer hardly changes. The common layer of the magnesium aluminum carbonate double-layer tablet can be completely peeled off from the sustained-release layer in about 30 seconds and sink into the lower layer, quickly neutralizing gastric acid and taking effect quickly. At the same time, the sustained-release layer has a release time of up to 4 hours after forming a floating layer, which proves that the magnesium aluminum carbonate double-layer tablet has a sustained-release effect within 4 hours after administration, and can effectively prolong the treatment time of patients with gastric ulcer and duodenal ulcer.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceuticals, and in particular to a hydrotalcite double-layer tablet and a preparation method thereof. Background Art

[0002] Aluminum carbonate granules are a drug used for acute and chronic gastritis, gastric ulcer, duodenal ulcer, reflux esophagitis, stomach discomfort symptoms related to gastric acid, such as stomach pain, heartburn, acidic belching, fullness, and prevention of gastric mucosal damage caused by non-steroidal drugs. Aluminum carbonate is a compound formed by aluminum hydroxide, magnesium hydroxide, carbonate and water. It can quickly release aluminum carbonate after oral administration. Aluminum carbonate is a crystalline powder that is insoluble in water and has a layered network structure. After oral administration, it is not absorbed by the gastrointestinal tract but forms a multi-layered network lattice structure in the esophageal, gastric and duodenal mucosa, and is deposited on the mucosal surface to exert its effect. Mechanism of action: (1) Forming a protective layer to play a mechanical protective role, especially with stronger bonding to damaged mucosa; (2) Blocking the damage of various damaging factors to the gastric mucosa and neutralizing gastric acid. The multi-layered network lattice structure formed by aluminum carbonate acts as HCO 3 - reservoir, which can continuously release OH - , blocking H + It has a diffusion effect, regulates the pH in the stomach (pH=3-5), adsorbs histamine and bile acid, and has an adsorption rate of 100% for free bile acid. It can prevent the carcinogenic effect of bile acid, adsorb pepsin, block the erosion of gastric mucosa by pepsin, remove oxygen free radicals, reduce the damage of oxygen free radicals to gastric mucosa, and promote ulcer healing; (3) It upregulates various defense and repair factors of the gastric mucosal defense and repair system, increases the content of gastric mucus glycoprotein-hexosamine, and increases gastric mucosal prostaglandin E 2 It increases the synthesis of gastric mucosal blood supply, the amount of epidermal growth factor and fibroblast growth factor in gastric mucosal epithelial cells and the expression of two corresponding receptors.

[0003] At present, there are four dosage forms of aluminum carbonate magnesium granules, aluminum carbonate magnesium suspension, aluminum carbonate magnesium chewable tablets, and aluminum carbonate co-dry gel on the market. There are a total of 118 registered units in China. Among them, aluminum carbonate magnesium granules, tablets, and aluminum carbonate co-dry gel are common products with basically the same principles. The disadvantage is that they do not stay in the stomach for a long time. They are either rapidly released and produce effects quickly, but the effect is short-lived, or the drug is slowly released and has a long effect, but the onset is slow and the efficacy is not obvious. In other words, they cannot achieve the effects of timely treatment and long-term maintenance of therapeutic effects at the same time. Summary of the invention

[0004] The present invention aims to provide a hydrotalcite double-layer tablet.

[0005] Another object of the present invention is to provide a method for preparing a hydrotalcite double-layer tablet, which solves the problems of poor uniformity in the double-layer tablet structure and disordered release of hydrotalcite between the ordinary layer and the sustained-release layer, so that the hydrotalcite double-layer tablet can achieve the effect of timely treatment and long-term maintenance of the therapeutic effect.

[0006] The purpose of the present invention is achieved through the following technical solutions:

[0007] A double-layer aluminum carbonate tablet, characterized in that the double-layer tablet is obtained by pressing a common aluminum carbonate layer and a sustained-release aluminum carbonate layer, wherein the common aluminum carbonate layer contains aluminum carbonate as the main drug, and the auxiliary materials are fillers and disintegrants, and the sustained-release aluminum carbonate layer contains aluminum carbonate as the main drug, and the auxiliary materials are administration rate regulators, gastric floating additives, expanders, foaming agents and hydrophilic gels.

[0008] Furthermore, the filler includes one or more of lactose, mannitol, and microcrystalline cellulose.

[0009] Furthermore, the disintegrant is one or more of low-substituted hydroxymethyl cellulose and sodium carboxymethyl starch.

[0010] Furthermore, the administration rate regulator is one or more of lactose and mannitol.

[0011] Furthermore, the gastric floating additive includes one or more of glyceryl monostearate, stearyl alcohol, stearic acid and beeswax.

[0012] Furthermore, the swelling agent is one or more of gelatin and gum arabic.

[0013] Furthermore, the foaming agent is any one of sodium carbonate and sodium bicarbonate.

[0014] Furthermore, the hydrophilic gel includes one or more of hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (CMC-Na), polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA).

[0015] Furthermore, in terms of weight percentage, in the common hydrotalcite layer, hydrotalcite is present in an amount of 150 to 200 parts, filler is present in an amount of 60 to 77 parts, and disintegrant is present in an amount of 30 to 60 parts.

[0016] Furthermore, in terms of weight percentage, in the aluminum carbonate sustained-release layer, aluminum carbonate is 50 to 80 parts, the administration rate regulator is 20 to 30 parts, the gastric floating additive is 130 to 170 parts, the foaming agent is 80 to 150 parts, the expander is 85 to 105 parts, and the hydrophilic gel is 30 to 60 parts.

[0017] Preferably, in the common layer of magnesium aluminum carbonate, the filler in the auxiliary materials is lactose, and the disintegrant is low-substituted hydroxypropyl cellulose.

[0018] Preferably, in the aluminum carbonate sustained-release layer, aluminum carbonate is the main drug, the administration rate regulator in the auxiliary materials is mannitol, the gastric floating additive is stearic acid, the swelling agent is gelatin, the foaming agent is sodium carbonate, and the hydrophilic gel is HPMC.

[0019] Furthermore, in terms of weight percentage, in the ordinary hydrotalcite layer, hydrotalcite is present in an amount of 170 to 200 parts, lactose is present in an amount of 60 to 77 parts, and low-substituted hydroxypropyl cellulose is present in an amount of 30 to 60 parts.

[0020] Furthermore, in terms of weight percentage, in the hydrotalcite sustained-release layer, hydrotalcite is 50-80 parts, mannitol is 20-30 parts, stearic acid is 130-170 parts, sodium carbonate is 80-150 parts, gelatin is 85-105 parts, and HPMC is 30-60 parts.

[0021] The basic principle of the aluminum carbonate double-layer tablet of the present invention for treating gastric ulcer and duodenal ulcer is that when the ordinary layer of aluminum carbonate encounters gastric juice, it quickly disintegrates under the action of the disintegrant low-substituted hydroxypropyl cellulose and peels off from the aluminum carbonate sustained-release layer. At the same time, the gelatin in the aluminum carbonate sustained-release layer rapidly expands in volume under the action of the hydrophilic gel hydroxypropyl methylcellulose after encountering gastric juice. Under the dual effects of the disintegration of the ordinary layer of aluminum carbonate and the expansion of the gelatin in the sustained-release layer, the sustained-release layer quickly falls off from the surface of the ordinary layer of aluminum carbonate, and the ordinary layer sinks and adheres to the stomach surface under the gravity of aluminum carbonate, quickly takes effect to protect the gastric mucosa from being eroded by gastric acid. The aluminum carbonate reacts with gastric acid to generate gas to form a boosting force, which pushes the aluminum carbonate sustained-release layer in the opposite direction to move in the stomach in an undirected manner, so that the sustained-release layer can release drugs at different positions in the stomach. The mannitol / lactose in the sustained-release layer in a migratory state dissolves evenly when it meets water, forming certain evenly distributed pores on the surface of the sustained-release layer, allowing gastric acid to fully contact with the foaming agent sodium carbonate, reacting to produce carbon dioxide. The carbon dioxide gas and stearic acid work together to allow the sustained-release layer to float in the stomach for a long time, forming a gastric floating tablet, allowing the carbon dioxide generated by the reaction to shuttle evenly in the sustained-release layer, further penetrating the pores generated by the dissolution of mannitol to form holes, forming a sustained-release channel, and regulating the release rate of aluminum carbonate in the sustained-release layer, achieving a continuous and slow release of the aluminum carbonate component, neutralizing gastric acid to achieve a sustained release and continuous treatment of the stomach and duodenum.

[0022] A method for preparing a hydrotalcite double-layer tablet is characterized by comprising the following steps:

[0023] Step (1) Raw material processing: the raw and auxiliary hydrotalcite, filler and disintegrant in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, drug delivery rate regulator, gastric floating additive, foaming agent, expander and hydrophilic gel in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;

[0024] Step (2) preparing mixed powder: placing the raw materials of the common layer of aluminum carbonate, aluminum carbonate, filler and disintegrant in a three-dimensional motion mixer and mixing for 10 minutes to obtain the total mixed powder 1 for tableting; adding the raw materials of the sustained-release layer of aluminum carbonate, aluminum carbonate, drug delivery rate regulator, gastric floating additive, foaming agent, expander and hydrophilic gel to the three-dimensional motion mixer and mixing for 15 minutes to obtain the total mixed powder 2 for tableting;

[0025] Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.

[0026] Furthermore, in the step (1), the filler in the common layer of hydrotalcite is lactose, and the disintegrant is low-substituted hydroxypropyl cellulose.

[0027] Furthermore, in the step (1) of the aluminum carbonate sustained-release layer, aluminum carbonate is the main drug, the administration rate regulator in the auxiliary materials is mannitol, the gastric floating additive is stearic acid, the swelling agent is gelatin, the foaming agent is sodium carbonate, and the hydrophilic gel is HPMC.

[0028] Furthermore, in terms of weight percentages, in the ordinary layer of aluminum carbonate in step (2), aluminum carbonate is 170 to 200 parts, lactose is 60 to 77 parts, and low-substituted hydroxypropyl cellulose is 30 to 60 parts.

[0029] Furthermore, in terms of parts by mass, in the hydrotalcite sustained-release layer of step (2), hydrotalcite is 50 to 80 parts, mannitol is 20 to 30 parts, stearic acid is 130 to 170 parts, sodium carbonate is 80 to 150 parts, gelatin is 85 to 105 parts, and HPMC is 30 to 60 parts.

[0030] The most specific method for preparing a hydrotalcite double-layer tablet is as follows:

[0031] Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;

[0032] Step (2) preparing a mixed powder: according to the weight percentage, 170-200 parts of the raw materials of the normal layer of the sieved aluminum carbonate, 60-77 parts of lactose, and 30-60 parts of low-substituted hydroxypropyl cellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 50-80 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 30-40 parts of mannitol, 130-170 parts of stearic acid, 80-150 parts of sodium carbonate, 85-105 parts of gelatin, and 30-60 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;

[0033] Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.

[0034] The present invention has the following technical effects:

[0035] The aluminum carbonate magnesium double-layer tablet prepared by the present invention has a rapid onset of treatment for gastric and duodenal ulcers, is more durable, and has better patient compliance. The stability test results show that the stability is within 24 months, and the main drug content of the common layer and the sustained-release layer of the product hardly changes. The common layer of the aluminum carbonate magnesium double-layer tablet can be completely peeled off from the sustained-release layer and sink into the lower layer in about 30 seconds, quickly neutralizes gastric acid, and takes effect quickly. At the same time, the release time of the sustained-release layer after forming a floating layer is as long as 4 hours, which proves that the aluminum carbonate magnesium double-layer tablet has a sustained-release effect within 4 hours after administration, and can effectively prolong the treatment time of patients with gastric ulcers and duodenal ulcers. The preparation method is simple and feasible and is worthy of promotion. DETAILED DESCRIPTION

[0036] The present invention is described in detail below through examples. It is necessary to point out that the following examples are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. Those skilled in the art can make some non-essential improvements and adjustments to the present invention based on the above-mentioned contents of the present invention.

[0037] Example 1

[0038] A method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:

[0039] Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;

[0040] Step (2) preparing a mixed powder: according to the weight percentage, 200 parts of the raw materials of the normal layer of the sieved aluminum carbonate, 60 parts of lactose, and 50 parts of low-substituted hydroxypropyl cellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 50 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 20 parts of mannitol, 140 parts of stearic acid, 80 parts of sodium carbonate, 100 parts of gelatin, and 30 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;

[0041] Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.

[0042] Example 2

[0043] A method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:

[0044] Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;

[0045] Step (2) preparing a mixed powder: according to the weight percentage, 170 parts of the raw materials of the ordinary layer of the sieved aluminum carbonate, 77 parts of lactose, and 30 parts of low-substituted hydroxypropyl cellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 80 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 30 parts of mannitol, 170 parts of stearic acid, 150 parts of sodium carbonate, 85 parts of gelatin, and 60 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;

[0046] Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.

[0047] Example 3

[0048] A method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:

[0049] Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;

[0050] Step (2) preparing a mixed powder: according to the weight percentage, 180 parts of the raw materials of the ordinary layer of the sieved aluminum carbonate, 70 parts of lactose, and 60 parts of low-substituted hydroxypropyl methylcellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 70 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 25 parts of mannitol, 130 parts of stearic acid, 100 parts of sodium carbonate, 105 parts of gelatin, and 50 parts of HPMC are added to the three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;

[0051] Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.

[0052] Experiment 1:

[0053] Artificial gastric juice experiments were carried out using ordinary hydrotalcite tablets and the hydrotalcite double-layer tablets prepared by the present invention.

[0054] Preparation of simulated artificial gastric juice:

[0055] 1. Take 1 mol / mL dilute hydrochloric acid, dilute with water, adjust the pH to 1.0, add 25 parts of pepsin, 12.5 parts of sodium chloride and 12.5 parts of potassium chloride to 2.5L solution, stir and dissolve completely, and filter with a 0.2um sterile filter membrane to obtain simulated artificial gastric juice.

[0056] 2. Place the simulated artificial gastric juice in a glass cup, and place the glass cup in a water bath insulation system to ensure that the temperature of the simulated artificial filtrate is around 37°C.

[0057] 3. Take 500mL of simulated artificial gastric juice with a pH of 1.0 and add it to the dissolution cup. Add 1 compressed aluminum carbonate double-layer tablet, adjust the stirring speed to 50 rpm, stir and observe the phenomenon. The results are shown in Table 1:

[0058] Table 1:

[0059]

[0060] Experiment 2:

[0061] The hydrotalcite bilayer tablets prepared by the present invention were subjected to dissolution test and long-term stability test.

[0062] 1. Test method: Refer to the stability test of Part II of the 2020 edition of the Chinese Pharmacopoeia

[0063] 2. Test conditions:

[0064] (1) Dissolution curve test: Dissolution curve test was performed on the retained samples at 0, 1, 2, 3, and 6 months under the condition of pH 1.2 to observe the change of dissolution rate.

[0065] (2) Long-term test temperature: 25±2℃; long-term test humidity: RH60%±10%

[0066] (3) Long-term test duration: 0, 3, 6, 9, 12, 18, 24 months

[0067] (4) Dissolution test observation time: 0, 1, 2, 3, 6

[0068] (5) Dissolution test method: The aluminum carbonate magnesium bilayer tablets prepared in Examples 1, 2, and 3 were tested for dissolution curves. The test method was based on the first method of the 2020 edition of the Pharmacopoeia Standard Operating Procedure, with 1000 ml of pH 1.2 salt buffer as the release medium, and the rotation speed was 100 turns per min. The blue method was operated according to the law. 5 ml of solution was taken after 5 min, 10 min, 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, and 360 min, respectively, and filtered. 5 ml of hydrochloric acid buffer at the same temperature was immediately added to the dissolution cup; 1 ml of the subsequent filtrate was accurately measured, placed in a 100 ml volumetric flask, diluted to the scale with hydrochloric acid buffer at pH 1.2, and shaken to obtain. The melting curve data obtained by the test are shown in Table 2.

[0069] Table 2: Dissolution curve statistics of hydrotalcite bilayer tablets

[0070]

[0071] From the dissolution curve data in the above table, it can be seen that hydrotalcite can reach a dissolution rate of more than 65% after dissolution for 10 minutes, and the highest can reach more than 80%, that is, it can achieve a rapid effect. After 10 minutes, the double-layer tablet begins to exert a slow release effect, and the release time can reach 4 hours. Compared with ordinary hydrotalcite tablets, granules, etc., it has a slow release effect, prolongs the efficacy, and can reduce the number of medications. In addition,

[0072] After 6 months of storage, the dissolution behavior did not change compared with 0 month.

[0073] Experiment 3: Long-term acid-reducing capacity and stability test

[0074] Take the hydrochloric acid titration of the hydrochloric acid double-layer tablets prepared in Examples 1-3, take an appropriate amount (equivalent to 0.5g of hydrochloric acid), accurately weigh, add a small amount of water to mix to form a uniform slurry, add water to make 100mL, accurately add 200mL of hydrochloric acid titration solution (0.1mol / L), stir at 37°C at a speed of 200 revolutions per minute for 1h, and test the amount of hydrochloric acid titration solution (0.1mol / L) consumed by 1g of hydrochloric acid titration solution as the antacidity. The specific antacidity test results are shown in Table 3.

[0075] Table 3:

[0076]

[0077]

[0078] Note: "--" means no test was performed.

[0079] Long-term tests show that there is no significant change in the properties, identification, content, microbial limit and other indicators of Examples 1, 2 and 3 of the product in the 24-month long-term test, so the quality of this product is stable in the 24-month long-term test.

[0080] Comparative Example 1:

[0081] Compared with Example 1, in the raw materials of the hydrotalcite sustained-release layer, sodium carbonate was replaced with an equal amount of lactose, and the other components remained unchanged.

[0082] The acid-suppressing power of the aluminum carbonate bilayer tablet prepared in comparative example 1 is 326.4 mL. Through the simulation of artificial gastric juice experiment, it is found that the aluminum carbonate bilayer tablet prepared in comparative example 1 is separated from the ordinary layer and the sustained-release layer at 30 seconds, and the ordinary layer is completely disintegrated. A small amount of bubbles are generated when the artificial gastric juice is just put into the artificial gastric juice. After the aluminum carbonate sustained-release layer is opened, the diffuse powder gradually sinks to the bottom of the bottle. At the same time, the sustained-release layer swims in the bottle without direction, and the surrounding bubbles do not change much. The sustained-release layer slowly sinks after floating for about 30 seconds, and the tablet gradually becomes smaller. Since there is no sodium carbonate reacting with the acid to generate gas to form a sustained-release channel, it depends on the expansion of gelatin in the sustained-release layer. The large proportion of mannitol and lactose dissolve in water, making the sustained-release layer structure unstable and quickly releasing drugs. At 150 minutes, the sustained-release layer completely disintegrates.

[0083] Comparative Example 2:

[0084] Compared with Example 1, the gelatin in the raw material of the hydrotalcite sustained-release layer of hydrotalcite was replaced with an equal amount of lactose, and the other components remained unchanged.

[0085] The acid antacidity of the aluminum carbonate magnesium bilayer tablet prepared in Comparative Example 2 was 331.9 mL. Through the simulated artificial gastric juice experiment, it was found that the ordinary layer and the sustained-release layer of the aluminum carbonate magnesium bilayer tablet prepared in Comparative Example 2 were separated at 38 s, and the ordinary layer was completely disintegrated. A small amount of bubbles are generated when the artificial gastric juice is just put into the bottle. After the aluminum carbonate sustained-release layer pops up, the diffused powder gradually sinks to the bottom of the bottle. At the same time, the sustained-release layer swims in the bottle without direction, and the number of bubbles around it increases, floating in the beaker, but the floating time is short, only maintaining 42 seconds, and then slowly sinking, the sinking speed is slightly slower than that of comparative example 1. As time goes by, the sustained-release layer tablets gradually become smaller. Due to the absence of gelatin to promote the expansion of the hydrogel, the dissolution of the mannitol and lactose inside is hindered, and the reaction of sodium carbonate with acid is slow, making the sustained release of the drug difficult. At 290 minutes, the floating sustained-release layer completely disintegrates. Such a sustained-release rate causes the aluminum carbonate in the sustained-release layer to be unable to connect with the efficacy of the aluminum carbonate in the ordinary layer, resulting in a fault, and the amount of aluminum carbonate in the sustained-release layer is small, and it cannot independently exert a more obvious efficacy.

[0086] Experiment 4: In vitro acid resistance test

[0087] According to Rossett Rice body acid resistance test: 30mL water and 70ml 0.1mol / L hydrochloric acid solution are added to the reaction vessel, and the reaction solution is controlled at 37°C by a magnetic heating stirrer and a contact thermometer, and magnetic stirring is performed at a stirring speed of 400r / min. The change of pH value in the reaction vessel is measured, and a constant flow pump is used to pump 37°C constant temperature 0.1mol / L hydrochloric acid solution into the reaction vessel at a speed of (1±0.1)mL / min. When the aluminum carbonate magnesium double-layer tablets prepared in Examples 1-3 and Comparative Examples 1 and 2 are added, the constant flow pump and magnetic stirrer are immediately turned on, and the time when pH reaches 3 and the duration of holding are recorded. The test results are shown in Table 4.

[0088] Table 4:

[0089] Aluminum carbonate double layer tablets Time taken for pH to reach 3 The pH is maintained at 3-5 Example 1 17s 4.3h Example 2 19s 4.2h Example 3 19s 4.4h Comparative Example 1 28s 2.6h Comparative Example 2 24s 2.3h

[0090] As can be seen from the above table, the aluminum carbonate magnesium double-layer tablet prepared by the present invention takes a shorter time to reach pH 3, which can achieve the purpose of rapid onset of effect, and maintains pH 3-5 for a longer time, which can achieve a long-term anti-acid effect.

Claims

1. A double-layer aluminum carbonate magnesium sheet, characterized in that: The double-layer tablet is obtained by pressing a common aluminum carbonate layer and a sustained-release aluminum carbonate layer. In the common aluminum carbonate layer, aluminum carbonate is the main drug, and the auxiliary materials are fillers and disintegrants. In the sustained-release aluminum carbonate layer, the main drug is aluminum carbonate, and the auxiliary materials are a drug administration rate regulator, a gastric floating additive, a swelling agent, a foaming agent and a hydrophilic gel. The filler is lactose, the disintegrant is low-substituted hydroxymethyl cellulose, the drug administration rate regulator is mannitol, the gastric floating additive includes stearic acid, and the swelling agent is gelatin. The foaming agent is sodium carbonate, and the hydrophilic gel includes hydroxypropyl methylcellulose (HPMC). Calculated by weight, in the ordinary hydrotalcite layer, hydrotalcite is 170-200 parts, lactose is 60-77 parts, and low-substituted hydroxymethylcellulose is 30-60 parts. In the hydrotalcite sustained-release layer, hydrotalcite is 50-80 parts, mannitol is 20-30 parts, stearic acid is 130-170 parts, sodium carbonate is 80-150 parts, gelatin is 85-105 parts, and HPMC is 30-60 parts.

2. A method for preparing a hydrotalcite double-layer tablet, characterized in that: Proceed as follows: Step (1) Raw material processing: the raw materials of hydrotalcite, filler and disintegrant in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials of hydrotalcite, drug delivery rate regulator, gastric floating additive, foaming agent, expander and hydrophilic gel in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use; The main drug in the common layer of aluminum carbonate is aluminum carbonate, the filler is lactose, the disintegrant is low-substituted hydroxypropyl cellulose, the aluminum carbonate is 170-200 parts, the lactose is 60-77 parts, and the low-substituted hydroxypropyl cellulose is 30-60 parts; in the aluminum carbonate aluminum sustained-release layer, aluminum carbonate is the main drug, the drug delivery rate regulator in the auxiliary materials is mannitol, the gastric floating additive is stearic acid, the expander is gelatin, the foaming agent is sodium carbonate, the hydrophilic gel is HPMC, the aluminum carbonate is 50-80 parts, the mannitol is 20-30 parts, the stearic acid is 130-170 parts, the sodium carbonate is 80-150 parts, the gelatin is 85-105 parts, and the HPMC is 30-60 parts; Step (2) preparing a mixed powder: placing the sieved raw materials of the normal layer of the aluminum carbonate, the filler and the disintegrant in a three-dimensional motion mixer and mixing for 10 minutes to obtain the total mixed powder 1 for tableting; placing the sieved raw materials of the sustained-release layer of the aluminum carbonate, the aluminum carbonate, the drug delivery rate regulator, the gastric floating additive, the foaming agent, the expander and the hydrophilic gel in the three-dimensional motion mixer and mixing for 15 minutes to obtain the total mixed powder 2 for tableting; Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and press the tablets to obtain the tablets.

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