Lansoprazole sodium bicarbonate capsule and preparation process thereof

Abstract

The invention belongs to the field of pharmaceutical preparations, and discloses a lansoprazole sodium bicarbonate capsule and a preparation process thereof, and the preparation process comprises the following steps: firstly, pressing lansoprazole and auxiliary materials into a tablet core; directly tabletting the hydroxypropyl methylcellulose phthalate, the auxiliary materials and the tablet core again to obtain an enteric-coated layer; and finally, carrying out third-time tabletting on sodium bicarbonate, auxiliary materials and the secondarily-pressed tablet core, and pressing into the micro-tablet which sequentially comprises the lansoprazole tablet core, the enteric-coated layer and the sodium bicarbonate quick-acting layer from inside to outside. According to the lansoprazole sodium bicarbonate capsule prepared through the method, after a patient takes the capsule, the sodium bicarbonate layer in the medicine disintegrates rapidly, the concentration of gastric acid is reduced rapidly, pain of the patient is reduced, then lansoprazole wrapping the enteric layer enters the intestinal tract to be released, the gastric acid releasing capacity of gastric cells is reduced, and the symptoms are treated firstly and then the root causes are treated.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations and relates to a lansoprazole capsule preparation, in particular to a lansoprazole sodium bicarbonate capsule and a preparation process thereof. Background Art

[0002] With the increase of average human life expectancy and the decrease of swallowing ability with aging, oral tablet administration has become a problem of concern. It is estimated that about 50% of people have difficulty swallowing tablets and capsules, which affects the compliance of drug treatment. Lansoprazole is a new type of drug that inhibits gastric acid secretion. It is the second proton pump inhibitor anti-ulcer drug after omeprazole. In particular, it is significantly better than omeprazole, which is currently widely used in clinical practice, in the treatment of duodenal ulcer (DU). In actual use, patients usually need to take lansoprazole and sodium bicarbonate separately, which will cause the pain of taking the medicine twice.

[0003] Existing prazole drugs are mostly coated to form an enteric layer. The coating cannot cover all the coating liquid, which will result in large losses. At the same time, the coating also causes great pollution to the air discharged by the coating machine. Even if air purification equipment is used, the air pollution problem cannot be completely eliminated. In addition, the better the purification effect, the cost will increase exponentially. Summary of the invention

[0004] The present invention aims to solve the inconvenience of taking existing prazole drugs and the above technical problems existing in the production process, and provides a lansoprazole sodium bicarbonate capsule and a preparation process thereof.

[0005] To achieve the above object, the present invention adopts the following technical solutions:

[0006] The first aspect of the present invention is to provide a preparation process of lansoprazole sodium bicarbonate capsules, which comprises the following steps: firstly pressing lansoprazole and auxiliary materials into tablet cores; then directly pressing the tablet cores again using hydroxypropyl methylcellulose phthalate, auxiliary materials and the tablet cores to form enteric layers; and finally pressing sodium bicarbonate, auxiliary materials and the tablet cores compressed twice for a third time to form micro-tablets which are, from the inside out, lansoprazole tablet cores, enteric layers and sodium bicarbonate quick-acting layers.

[0007] Preferably, the preparation process of the lansoprazole sodium bicarbonate capsules comprises the following steps:

[0008] (I) Preparation of Lansoprazole Tablet Core Granules

[0009] Add the prescribed amount of lansoprazole, microcrystalline cellulose, poloxamer 188, calcium hydrogen phosphate, and magnesium stearate into a high-efficiency mixing granulator, turn on the stirring paddle, mix evenly, and set aside;

[0010] (II) Preparation of enteric-layered granules

[0011] Use appropriate amount of ethanol / water to dissolve Hydroxypropyl methylcellulose phthalate to obtain a mixed solution for later use;

[0012] Add the prescribed amount of lactose into a high-efficiency mixing granulator, turn on the stirring paddle, and add the above mixed liquid at a uniform speed while stirring. After the addition of liquid is completed, turn on the granulating knife and granulate for several minutes to obtain wet granules;

[0013] The wet granules are spread on a plate and put into a drying room, where they are dried at 40-50°C;

[0014] (III) Preparation of Sodium Bicarbonate Mixed Powder

[0015] Add the prescribed amount of sodium bicarbonate, microcrystalline cellulose and cross-linked carboxymethyl cellulose sodium into a high-efficiency mixing granulator, mix evenly and set aside;

[0016] (IV) Tablet pressing

[0017] A multi-tablet press is used, and Φ9.5 mm flat punch tablets are loaded; Lansoprazole granules are added to the first hopper to compress the center layer tablets; enteric layer granules are added to the second hopper to compress the enteric layer; sodium bicarbonate mixed powder is added to the third hopper to compress the sodium bicarbonate quick-acting layer; and micro tablets with three layers of tablets compressed from the inside to the outside are obtained;

[0018] (V) Capsule filling

[0019] The compressed micro-tablets are filled into 0# gelatin capsules to prepare lansoprazole sodium bicarbonate capsules.

[0020] Preferably, in step (i), the prescription of the lansoprazole core granules is:

[0021]

[0022] Preferably, in step (ii), the formula of the enteric-coated granules is:

[0023] Hydroxypropyl methylcellulose phthalate 0.025kg

[0024] Lactose 0.025kg

[0025] Ethanol / water (8:2) appropriate amount.

[0026] Preferably, in step (iii), the formula of the sodium bicarbonate mixed powder is as follows, based on 10,000 micro-tablets:

[0027] Sodium bicarbonate 0.25kg

[0028] Croscarmellose sodium 0.02kg

[0029] 0.25kg of microcrystalline cellulose.

[0030] Preferably, in step (iv), the capsule filling prescription is:

[0031] 1 gelatin capsule

[0032] Lansoprazole sodium bicarbonate microtablets 0.9-1.0g.

[0033] Preferably, in step (i), the mixing process of the high-efficiency mixing granulator is: mixing speed 60-80 rpm and mixing time 3-5 min.

[0034] Preferably, in step (ii), the mixing process of the high-efficiency mixing granulator is: mixing speed 60-80 rpm and mixing time 5-10 min.

[0035] Preferably, in step (iv), the tablet pressing process of the tablet press is: a speed of 20 to 40 rpm and a main pressing pressure of 20 to 40 KN.

[0036] The second aspect of the present invention is to provide a lansoprazole sodium bicarbonate capsule prepared by the above process, comprising a three-layer micro-tablet formed by sequentially compressing a lansoprazole core, an enteric layer, and a sodium bicarbonate quick-acting layer from the inside out.

[0037] The present invention adopts the above technical solution, which has the following technical effects compared with the prior art:

[0038] (1) The present invention adopts a multiple tableting process to compress lansoprazole and sodium bicarbonate into one tablet, and the patient only needs to take it once, which reduces the pain of the patient;

[0039] (2) The present invention uses tabletting to directly compress the enteric layer instead of coating to form the enteric layer, which reduces the loss of raw materials and auxiliary materials, reduces environmental pollution and purification costs, and at the same time, tableting is more controllable and stable than the coating process, which is more beneficial to the quality assurance of the drug;

[0040] (3) The sodium bicarbonate layer in the microtablet of the present invention is directly compressed powder, wherein the microcrystalline cellulose and cross-linked sodium carboxymethyl cellulose can produce a rapid disintegration effect, which can quickly disintegrate and diffuse the sodium bicarbonate layer, effectively reduce the pH value of gastric acid, and quickly reduce the pain of the patient;

[0041] (4) In the lansoprazole core of the microtablet of the present invention, lansoprazole can be rapidly dissolved under the solubilizing effect of poloxamer 188, and has high bioavailability. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 The dissolution curves of lansoprazole sodium bicarbonate capsules prepared in the examples and comparative examples of the present invention in pH 6.8 phosphate buffer are shown. DETAILED DESCRIPTION

[0043] The present invention is described in detail and specifically by specific examples below to provide a better understanding of the present invention, but the following examples do not limit the scope of the present invention.

[0044] Example 1

[0045] A lansoprazole sodium bicarbonate capsule, calculated as 10,000 micro-tablets, adopts the following prescription:

[0046] (I) Lansoprazole tablet core layer prescription:

[0047]

[0048] (II) Enteric-coated formulation

[0049] Hydroxypropyl methylcellulose phthalate 0.025kg

[0050] Lactose 0.025kg

[0051] Ethanol / water (8:2) appropriate amount

[0052] (III) Sodium bicarbonate layer prescription

[0053] Sodium bicarbonate 0.25kg

[0054] Croscarmellose sodium 0.02kg

[0055] Microcrystalline cellulose 0.25kg

[0056] (IV) Capsule prescription (1 capsule)

[0057] 1 gelatin capsule

[0058] Lansoprazole sodium bicarbonate microtablets 0.9-1.0g.

[0059] Based on the above prescription, the preparation process of the lansoprazole sodium bicarbonate capsules specifically includes the following steps:

[0060] (I) Preparation of Lansoprazole Granules

[0061] Add the prescribed amount of lansoprazole, microcrystalline cellulose, poloxamer 188, and magnesium stearate into a high-efficiency mixing granulator, turn on the stirring paddle, mix for 3 minutes, and set aside;

[0062] (II) Preparation of enteric-layered granules

[0063] Use an appropriate amount of ethanol / water (8:2) to dissolve hydroxypropyl methylcellulose phthalate to obtain a mixed solution for later use;

[0064] Add the prescribed amount of lactose into a high-efficiency mixing granulator, turn on the stirring paddle, and add the above mixed liquid at a uniform speed while stirring. After the addition of liquid is completed, turn on the granulating knife and granulate for several minutes to obtain wet granules;

[0065] Put the wet granules into the drying room and dry them at 40-50℃ for later use;

[0066] (III) Preparation of Sodium Bicarbonate Mixed Powder

[0067] Mix the prescribed amount of lansoprazole, microcrystalline cellulose, and croscarmellose sodium for 5 minutes and set aside;

[0068] (IV) Tablet pressing

[0069] Use a multi-tablet press to load Φ9.5mm flat punch tablets; add lansoprazole granules to the first hopper to compress the center layer tablets, add enteric layer granules to the second hopper to compress the enteric layer, and add sodium bicarbonate mixed powder to the third hopper to compress the sodium bicarbonate quick-acting layer;

[0070] (V) Capsule filling

[0071] The compressed micro-tablets are filled into 0# gelatin capsules to prepare lansoprazole sodium bicarbonate capsules.

[0072] Comparative Example 1

[0073] A lansoprazole sodium bicarbonate capsule, calculated as 10,000 tablets, adopts the following prescription:

[0074] (I) Lansoprazole tablet core layer prescription:

[0075]

[0076] (II) Enteric-coated layer prescription:

[0077]

[0078] Based on the above prescription, the preparation process of the lansoprazole sodium bicarbonate capsules specifically includes the following steps:

[0079] (I) Preparation of Lansoprazole Sodium Bicarbonate Granules

[0080] Add the prescribed amount of lansoprazole, microcrystalline cellulose, sodium bicarbonate, and magnesium stearate into a high-efficiency mixing granulator, turn on the stirring paddle, mix for 5 minutes, and set aside;

[0081] (II) Tablet pressing

[0082] The granules are compressed into tablets to prepare lansoprazole sodium bicarbonate tablet cores.

[0083] (III) Coating

[0084] Prepare enteric coating solution:

[0085] Add appropriate amount of purified water to the prescribed amount of talcum powder and shear in a high-speed shearing machine for 5 minutes for later use;

[0086] Add a proper amount of purified water to the prescribed amount of titanium dioxide in a high-speed shearing machine, shear for 5 minutes, and set aside;

[0087] Put the remaining purified water in a mixing bucket and add L30D-55 while stirring until it is evenly mixed;

[0088] Slowly add triethyl citrate into the above-mentioned enteric coating layer material under stirring;

[0089] Add the prepared talcum powder solution and titanium dioxide solution into the material of the enteric coating layer under stirring to prepare an enteric coating solution for later use;

[0090] Enteric layer:

[0091] Place the lansoprazole sodium bicarbonate tablet core in a fluidized bed boiling coating pot, heat to about 40°C, and start coating with an enteric layer coating solution;

[0092] Control the spray gun flow, spray speed, inlet air temperature, material temperature, fan frequency and atomization pressure;

[0093] After coating is completed, boil for a few minutes to dry, release the material, spread it out in a drying room and dry it at 40°C for 3 hours.

[0094] Comparative Example 2

[0095] A lansoprazole sodium bicarbonate capsule, calculated as 10,000 micro-tablets, adopts the following prescription:

[0096] (I) Lansoprazole tablet core layer prescription:

[0097] Lansoprazole 0.03kg

[0098] Microcrystalline cellulose 0.03kg

[0099] Magnesium stearate 0.0005kg

[0100] (II) Enteric-coated formulation

[0101] Hydroxypropyl methylcellulose phthalate 0.025kg

[0102] Lactose 0.025kg

[0103] Ethanol / water (8:2) appropriate amount

[0104] (III) Sodium bicarbonate layer prescription

[0105] Sodium bicarbonate 0.25kg

[0106] Croscarmellose sodium 0.02kg

[0107] Microcrystalline cellulose 0.25kg

[0108] (IV) Capsule prescription (1 capsule)

[0109] 1 gelatin capsule

[0110] Lansoprazole sodium bicarbonate microtablets 0.9-1.0g.

[0111] Based on the above prescription, the preparation process of the lansoprazole sodium bicarbonate capsules specifically includes the following steps:

[0112] (I) Preparation of Lansoprazole Granules

[0113] Add the prescribed amount of lansoprazole, microcrystalline cellulose and magnesium stearate into a high-efficiency mixing granulator, turn on the stirring paddle, mix for 3 minutes, and set aside;

[0114] (II) Preparation of enteric-layered granules

[0115] Use an appropriate amount of ethanol / water (8:2) to dissolve hydroxypropyl methylcellulose phthalate to obtain a mixed solution for later use;

[0116] Add the prescribed amount of lactose into a high-efficiency mixing granulator, turn on the stirring paddle, and add the above mixed liquid at a uniform speed while stirring. After the addition of liquid is completed, turn on the granulating knife and granulate for several minutes to obtain wet granules;

[0117] Put the wet granules into the drying room and dry them at 40-50℃;

[0118] (III) Preparation of Sodium Bicarbonate Mixed Powder

[0119] Mix the prescribed amount of lansoprazole, microcrystalline cellulose, and croscarmellose sodium for 5 minutes and set aside;

[0120] (IV) Tablet pressing

[0121] Use a multi-tablet press to load Φ9.5mm flat punch tablets; add lansoprazole granules to the first hopper to compress the center layer tablets, add enteric layer granules to the second hopper to compress the enteric layer, and add sodium bicarbonate mixed powder to the third hopper to compress the sodium bicarbonate quick-acting layer;

[0122] (V) Capsule filling

[0123] The compressed micro-tablets are filled into 0# gelatin capsules to prepare lansoprazole sodium bicarbonate capsules.

[0124] Experimental verification:

[0125] Lansoprazole sodium bicarbonate quick-acting tablets prepared in Example 1, Comparative Example 1 and Comparative Example 2 were divided into three groups, and dissolution tests were performed at various in vitro pHs. Specifically, the tablets were simulated for release in 0.005 mol / L hydrochloric acid + 0.3% pepsin solution (simulating gastric juice) and pH 6.8 buffer (simulating the environment of the small intestine), respectively, using the paddle method at 75 rpm. The dissolution data of each group are shown in Tables 1, 2 and 3 below, and the dissolution curves of each group in pH 6.8 buffer are shown in Tables 1, 2 and 3 below, and the dissolution curves of each group in pH 6.8 buffer are shown in Tables 1, 2 and 3 below. Figure 1 shown.

[0126] Table 1 Dissolution data of three groups of lansoprazole sodium bicarbonate quick-acting tablets under different simulation conditions in Example 1

[0127]

[0128] Table 2 Dissolution data of three groups of lansoprazole sodium bicarbonate quick-acting tablets under different simulation conditions in Comparative Example 1

[0129]

[0130] Table 3 Dissolution data of three groups of lansoprazole sodium bicarbonate quick-acting tablets under different simulation conditions in Comparative Example 2

[0131]

[0132]

[0133] Summary: From the in vitro simulation, it can be seen that when the example drug enters the gastric juice (PH1.0), the drug quickly disintegrates and releases sodium bicarbonate, neutralizing the gastric juice pH to a more suitable level; at the same time, the enteric layer plays a protective role, ensuring that the drug is acid-resistant in the stomach for more than 2 hours. Generally, after more than 2 hours, the drug will enter the intestine (PH6.8), at which time the enteric layer dissolves and lansoprazole begins to be released. Under the solubilizing effect of poloxamer 188, the solubility in 15 minutes is ≥85%, which meets the rapid dissolution standard of the drug, indicating that the drug can be released quickly and has high bioavailability.

[0134] Compared with Comparative Example 1, the embodiment can quickly disintegrate and diffuse the sodium bicarbonate layer when the drug enters the stomach, effectively reduce the pH value of gastric acid, and quickly reduce the pain of the patient, while Comparative Example 1 is a conventional enteric layer coated tablet, which cannot reduce the pH value of gastric acid when entering the stomach, relieve symptoms, and requires other drugs for treatment, which increases the pain of patients taking the medicine;

[0135] Compared with Comparative Example 2, the dissolution rate of lansoprazole in the example in the intestine (pH 6.8) is ≥85% in 15 minutes, while the dissolution rate of Comparative Example 2 is about 35% in 15 minutes and about 75% in 30 minutes. It can be seen that the example has a fast efficacy and high bioavailability.

[0136] The specific embodiments of the present invention are described in detail above, but they are only examples, and the present invention is not limited to the specific embodiments described above. For those skilled in the art, any equivalent modifications and substitutions made to the present invention are also within the scope of the present invention. Therefore, the equalization changes and modifications made without departing from the spirit and scope of the present invention should be included in the scope of the present invention.

Claims

1. A preparation process of lansoprazole sodium bicarbonate capsules, characterized in that: First, lansoprazole and auxiliary materials are compressed into tablet cores; then, hydroxypropyl methylcellulose phthalate, auxiliary materials and tablet cores are directly compressed again to form enteric layers; finally, sodium bicarbonate, auxiliary materials and the tablet core compressed twice are compressed for the third time to form micro-tablets which are, from the inside to the outside, lansoprazole tablet core, enteric layer and sodium bicarbonate quick-acting layer.

2. The preparation process of lansoprazole sodium bicarbonate capsules according to claim 1, characterized in that: The steps include: (I) Preparation of Lansoprazole Tablet Core Granules Add the prescribed amount of lansoprazole, microcrystalline cellulose, poloxamer 188, calcium hydrogen phosphate, and magnesium stearate into a high-efficiency mixing granulator, turn on the stirring paddle, mix evenly, and set aside; (II) Preparation of enteric-layered granules Use appropriate amount of ethanol / water to dissolve Hydroxypropyl methylcellulose phthalate to obtain a mixed solution for later use; Add the prescribed amount of lactose into a high-efficiency mixing granulator, turn on the stirring paddle, and add the above mixed liquid at a uniform speed while stirring. After the addition of liquid is completed, turn on the granulating knife and granulate for several minutes to obtain wet granules; Put the wet granules into the drying room and dry them at 40-50℃ for later use; (III) Preparation of Sodium Bicarbonate Mixed Powder Add the prescribed amount of sodium bicarbonate, microcrystalline cellulose and cross-linked carboxymethyl cellulose sodium into a high-efficiency mixing granulator, mix evenly and set aside; (IV) Tablet pressing A multi-tablet press is used, and Φ9.5 mm flat punch tablets are loaded; Lansoprazole granules are added to the first hopper to compress the center layer tablets; enteric layer granules are added to the second hopper to compress the enteric layer; sodium bicarbonate mixed powder is added to the third hopper to compress the sodium bicarbonate quick-acting layer; and micro tablets with three layers of tablets compressed from the inside to the outside are obtained; (V) Capsule filling The compressed micro-tablets are filled into 0# gelatin capsules to prepare lansoprazole sodium bicarbonate capsules.

3. The preparation process of lansoprazole sodium bicarbonate capsules according to claim 2, characterized in that: In step (a), the prescription of the lansoprazole core granules is:

4. The preparation process of lansoprazole sodium bicarbonate capsules according to claim 2, characterized in that: In step (ii), the formula of the enteric-coated granules is as follows, based on 10,000 micro-tablets: Hydroxypropyl methylcellulose phthalate 0.025kg Lactose 0.025kg Ethanol / water (8:2) appropriate amount.

5. The preparation process of lansoprazole sodium bicarbonate capsules according to claim 2, characterized in that: In step (iii), the prescription of the sodium bicarbonate mixed powder is as follows, based on 10,000 micro-tablets: Sodium bicarbonate 0.25kg Croscarmellose sodium 0.02kg 0.25kg of microcrystalline cellulose.

6. The preparation process of lansoprazole sodium bicarbonate capsules according to claim 2, characterized in that: In step (iv), the capsule filling prescription is: 1 gelatin capsule Lansoprazole sodium bicarbonate microtablets 0.9-1.0g.

7. The preparation process of lansoprazole sodium bicarbonate capsules according to claim 2, characterized in that: In step (i), the mixing process of the high-efficiency mixing granulator is: mixing speed 60-80 rpm and mixing time 3-5 min.

8. The preparation process of lansoprazole sodium bicarbonate capsules according to claim 2, characterized in that: In step (ii), the mixing process of the high-efficiency mixing granulator is: mixing speed 60-80 rpm and mixing time 5-10 min.

9. The preparation process of lansoprazole sodium bicarbonate capsules according to claim 2, characterized in that: In step (iv), the tablet pressing process of the tablet press is: a speed of 20 to 40 rpm and a main pressing pressure of 20 to 40 KN.

10. A lansoprazole sodium bicarbonate capsule prepared by the process according to any one of claims 1 to 9, characterized in that: The invention comprises a three-layer micro-tablet which is formed by sequentially compressing a lansoprazole core, an enteric layer and a sodium bicarbonate quick-acting layer from the inside out.

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