Preparation method of Lansuo capsule

Abstract

The invention discloses a preparation method of a lansoprazole capsule, and relates to the technical field of medicine preparation, the lansoprazole capsule is an enteric capsule, the formula comprises a main medicine layer, an isolation layer and a casing layer, the main medicine layer comprises 30.00 mg / grain of lansoprazole, 83.00 mg / grain of cane sugar pellet core, 22.50 mg / grain of heavy magnesium carbonate, 12.4 mg / grain of corn starch, 20.60 mg / grain of cane sugar, 10.50 mg / grain of hydroxypropyl cellulose and 177 mg / grain of purified water; the isolating layer comprises 10.80 mg / grain of heavy magnesium carbonate, 1.02 mg / grain of hydroxypropyl cellulose and 17.2 mg / grain of purified water; the casing layer comprises 128.0 mg / grain of methacrylic acid-ethyl acrylate copolymer aqueous dispersion, 3.8 mg / grain of PEG 6000, 3.8 mg / grain of titanium dioxide, 15.2 mg / grain of talcum powder and 254 mg / grain of purified water, and the problems that the drug release behavior, stability and uniformity are difficult to be consistent with those of a reference preparation, and the reliability of the drug curative effect is influenced are solved.

Description

Technical Field

[0001] The invention relates to the technical field of drug preparation, in particular to a preparation method of Lansuo capsules. Background Art

[0002] Lansoprazole is a proton pump inhibitor drug that mainly reduces gastric acid secretion by inhibiting the activity of H+ / K+-ATPase on the gastric mucosal wall cells. It is commonly used clinically to treat diseases related to excessive gastric acid secretion, such as gastric ulcer, duodenal ulcer, reflux esophagitis, and Zollinger-Ellison syndrome. It can effectively relieve symptoms such as heartburn and acid reflux and promote mucosal repair.

[0003] For example, the Chinese authorized patent "A Method for Preparing Lansoprazole Capsules" with announcement number CN103505436B contains the active ingredient lansoprazole and pharmaceutical excipients, wherein the pharmaceutical excipients are sodium bicarbonate, poloxamer, cross-linked carboxymethyl cellulose sodium, and magnesium stearate; its preparation method comprises the following steps: weighing the prescribed amount of lansoprazole, sieving it for later use; weighing the prescribed amount of sodium bicarbonate, sieving it for later use; weighing the prescribed amount of poloxamer 188, cross-linked carboxymethyl cellulose sodium, and magnesium stearate, passing through an 80-mesh sieve for later use; mixing sodium bicarbonate and lansoprazole evenly; adding cross-linked carboxymethyl cellulose sodium, poloxamer, and magnesium stearate respectively, and mixing them evenly; filling the powder into hollow capsules; and packaging to obtain the finished product.

[0004] However, the preparation process of lansoprazole enteric-coated capsules in the existing technology may have problems such as inconsistent prescription composition with the reference preparation and imprecise control of process parameters, which makes it difficult for the preparation quality, such as drug release behavior, stability, and uniformity, to be consistent with the reference preparation, affecting the reliability of drug efficacy. Therefore, it does not meet existing needs. In this regard, we propose a preparation method for lansoprazole capsules. Summary of the Invention

[0005] The purpose of the present invention is to provide a preparation method of Lansuo capsules to solve the problem raised in the above background technology that the drug release behavior, stability and uniformity are difficult to be consistent with the reference preparation, which affects the reliability of the drug efficacy.

[0006] To achieve the above object, the present invention provides the following technical solution: a method for preparing Lansuo capsules, wherein the Lansuo capsules are enteric-coated capsules, and the formulation comprises a main drug layer, a separation layer, and an enteric coating layer:

[0007] The main drug layer contains: lansoprazole 30.00 mg / pill, sucrose core 83.00 mg / pill, heavy magnesium carbonate 22.50 mg / pill, corn starch 12.4 mg / pill, sucrose 20.60 mg / pill, hydroxypropyl cellulose 10.50 mg / pill, and purified water 177 mg / pill;

[0008] The isolation layer contains: heavy magnesium carbonate 10.80 mg / pill, hydroxypropyl cellulose 1.02 mg / pill, and purified water 17.2 mg / pill;

[0009] The enteric coating layer contains: 128.0 mg / pill of methacrylic acid-ethyl acrylate copolymer aqueous dispersion, 3.8 mg / pill of PEG6000, 3.8 mg / pill of titanium dioxide, 15.2 mg / pill of talc, and 254 mg / pill of purified water.

[0010] Preferably, the preparation of the main drug layer and isolation layer pellet core comprises the following steps:

[0011] Step 1: Prepare a 7.6% adhesive solution by mixing hydroxypropyl cellulose with purified water;

[0012] Step 2: Evenly mix the main drug layer ingredients, lansoprazole, sucrose powder, corn starch, heavy magnesium carbonate, and low-substituted hydroxypropyl cellulose to obtain the main drug powder; evenly mix the heavy magnesium carbonate to obtain the isolation layer powder;

[0013] Step 3: Use a centrifugal granulator to coat the main drug powder and the isolation layer powder on the surface of the sucrose pill core in sequence, control the granulation temperature at 28-34°C, the spray gun atomization pressure at 0.2-0.3 MPa, and the feeding oscillation frequency at 50-80 Hz. After drying, sieve to retain the pill cores with a main drug layer of 16-30 mesh and an isolation layer of 16-24 mesh.

[0014] Preferably, the main drug powder is coated twice: first, 2 / 3 of the main drug powder is coated, and the fine powder below 80 mesh is collected after drying and sieving, and then coated together with the remaining 1 / 3 of the main drug powder on the surface of the pill core.

[0015] Preferably, the isolation layer pellet core is dried under the following conditions: drying in a vacuum drying oven at 40-45° C. until the moisture content is less than 3.0%, as measured by a rapid moisture drying instrument.

[0016] Preferably, the preparation of the enteric coating layer comprises the following steps:

[0017] Step 1: dissolving PEG6000, titanium dioxide, and talc in purified water, and adding methacrylic acid-ethyl acrylate copolymer aqueous dispersion to prepare an enteric coating solution;

[0018] Step 2: Use a fluidized bed coating machine to spray the enteric coating solution on the surface of the isolation layer pellets, control the inlet air temperature at 60°C, the material temperature at 31-35°C, and the spray gun atomization pressure at 0.2-0.3 MPa, dry until the moisture content is less than 3.0%, and then sieve to retain 16-24 mesh pellets.

[0019] Preferably, the amount of the enteric coating solution is prepared so as to increase the weight of the isolation layer pellets by 25%.

[0020] Preferably, the preheating conditions of the centrifugal granulator are: speed 50-95R / M, air inlet speed 2000-3000R / M, air inlet temperature 50-70°C, exhaust speed 500-1000R / M, and the initial trigger temperature of the material temperature sensor is 37°C.

[0021] The preheating conditions of the fluidized bed coating machine are: fan frequency 40-50HZ, air inlet temperature 60°C, and initial trigger temperature of the material temperature sensor 38°C.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. The present invention utilizes the same formulation as the reference preparation and, through a rational preparation process, ensures the quality consistency of the pharmaceutical preparation. During the preparation process, precise control of the preparation conditions of each layer, such as temperature, rotation speed, pressure, and flow rate, helps improve the stability and uniformity of the drug, ensuring effective drug release in the intestine and thus enhancing its efficacy. Furthermore, the preparation method is rational, feasible, and suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a diagram showing the steps for preparing the Lansuo capsules of the present invention. DETAILED DESCRIPTION

[0025] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0026] (1) Preparation of main drug and isolation layer pellets

[0027] 1. Preparation process

[0028] (1) Take the prescribed amount of hydroxypropyl cellulose for the main drug layer, soak it in the prescribed amount of purified water for about 12 hours, and then stir it with a pneumatic lift mixer to make a 7.6% solution as a binder;

[0029] (2) Take the prescribed amount of hydroxypropyl cellulose for the isolation layer, soak it in the prescribed amount of purified water for about 12 hours, and then stir it with a pneumatic lift mixer to make a 7.6% solution as a binder;

[0030] (3) Take the main drug layer and the isolation layer of sucrose in the prescribed amount and grind them with a grinder, pass them through a 100-mesh sieve, and set aside;

[0031] (4) Take the prescribed amount of lansoprazole, sucrose powder, corn starch, heavy magnesium carbonate, and low-substituted hydroxypropyl cellulose in the main drug layer respectively, add them into a three-dimensional mixer and mix for 5 minutes to obtain the main drug powder.

[0032] (5) Take the amount of heavy magnesium carbonate prescribed for the isolation layer, add it into a three-dimensional mixer and mix for 5 minutes. Mix well to obtain isolation layer powder for later use.

[0033] 2. Preparation process of main drug and isolation layer

[0034] (1) Preheating: Start the centrifugal granulator at a speed of 50-95 R / M, an inlet air speed of 2000-3000 R / M, an inlet air temperature of 50-70°C, and an exhaust air speed of 500-1000 R / M;

[0035] (2) When the centrifugal granulator material temperature sensor shows 37 ° C, add the prescribed amount of sucrose pellets, the material temperature will drop, and continue to heat the sucrose pellets. At this time, place the main drug layer powder in the lower hopper.

[0036] (3) When the material temperature shows 35-38 ° C, maintain the spray gun atomization pressure of 0.2-0.3Mpa, and control the flow rate of the adhesive peristaltic pump to 100-700ml / min, so that the adhesive is sprayed on the surface of the sucrose pill core. After the surface of the pill core is wetted, open the feed hopper of the centrifugal granulator to discharge the material, control the feeding oscillation frequency to 50-80Hz, and control the material temperature to 28-34 ° C, so that the main drug powder is adhered to the surface of the sucrose pill core.

[0037] (4) After 2 / 3 of the main drug powder is applied, turn off the adhesive peristaltic pump, continue spheronization and heating for 3-5 minutes, and remove the pill core;

[0038] (5) Place the pill core in a vacuum drying oven at 40-45°C and dry it.

[0039] (6) The dried pill cores containing the drug are sieved through 16, 30 and 80 mesh sieves respectively. The pill cores that pass through the 16 mesh sieve but not through the 30 mesh sieve are taken for later use; the powder below the 80 mesh sieve is collected for subsequent drug application.

[0040] (7) After cleaning and drying the centrifugal granulator, repeat steps (1), (2), and (3) to remove the remaining 1 / 3 of the main drug powder and the powder below 80 mesh in step (6).

[0041] (8) After the main drug layer powder is applied, the prepared isolation layer powder is placed in the centrifugal granulator hopper and begins to be discharged. The spray gun atomization pressure is maintained at 0.2-0.3 MPa, the adhesive peristaltic pump controls the flow rate at 100-700 ml / min, the feeding oscillation frequency is controlled at 50-80 Hz, and the material temperature is controlled at 28-34 ° C, so that the isolation layer powder adheres to the surface of the main pill core.

[0042] (9) After the isolation layer powder is discharged, turn off the adhesive peristaltic pump, continue spheronization and heating for 5-10 minutes, and remove the pellets;

[0043] (10) The isolation layer pellets are placed in a vacuum drying oven at 40°C to 45°C and dried until the moisture content is less than 3.0% (measured by a rapid moisture drying instrument).

[0044] (11) The dried isolation layer pellets are sieved through 16 and 24 mesh sieves respectively, and the isolation layer pellet cores that pass through the 16 mesh sieve but not the 24 mesh sieve are taken and set aside.

[0045] (2) Preparation of enteric coating pellet cores (prepared based on a 25% weight gain of pellets after screening the isolation layer)

[0046] 1. Preparation process

[0047] (1) Weigh the prescribed amount of purified water, add the prescribed amount of PEG6000, wait for it to completely dissolve, add the prescribed amount of titanium dioxide and talc, stir well, and set aside;

[0048] (2) Take the prescribed amount of methacrylic acid-ethyl acrylate copolymer aqueous dispersion, add it to the solution in the previous step, stir well, and prepare an enteric coating solution for later use;

[0049] 2. Preparation process of enteric coating pellets

[0050] (1) Start the fluidized bed fan at 40-50 Hz, the inlet air temperature at 60°C, preheat the pot, and when the material temperature sensor shows 38°C, place the isolation layer pellets into the fluidized bed coating machine.

[0051] (3) Heat the isolation layer pellets. When the material temperature shows 35°C, start the peristaltic pump for the enteric coating solution and set the spray gun atomization pressure to 0.2-0.3 MPa. The material temperature will drop. Control the peristaltic pump speed to 45-75 r / min, maintain the material temperature at 31-35°C, and continue to spray the enteric coating solution.

[0052] (4) After the casing solution is sprayed, turn off the peristaltic pump and set the air inlet temperature to 45-50°C to dry until the moisture content is less than 3% (measured by a rapid moisture drying instrument).

[0053] (5) The dried enteric coating layer pellets are sieved through 16 and 24 mesh sieves respectively, and the enteric coating layer pellets that pass through the 16 mesh sieve but not through the 24 mesh sieve are taken to be the enteric coating layer pellets.

[0054] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the invention can be embodied in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as illustrative and non-restrictive, and the scope of the invention is defined by the appended claims, not the foregoing description, and all variations within the meaning and range of equivalents of the claims are intended to be included therein. Any reference sign in a claim should not be construed as limiting the claim to which it relates.

Claims

1. A method for preparing Lansuo capsules, characterized in that: The Lansuo capsules are enteric-coated capsules, and the prescription composition includes a main drug layer, an isolation layer and an enteric coating layer: The main drug layer contains: lansoprazole 30.00 mg / pill, sucrose core 83.00 mg / pill, heavy magnesium carbonate 22.50 mg / pill, corn starch 12.4 mg / pill, sucrose 20.60 mg / pill, hydroxypropyl cellulose 10.50 mg / pill, and purified water 177 mg / pill; The isolation layer contains: heavy magnesium carbonate 10.80 mg / pill, hydroxypropyl cellulose 1.02 mg / pill, and purified water 17.2 mg / pill; The enteric coating layer contains: 128.0 mg / pill of methacrylic acid-ethyl acrylate copolymer aqueous dispersion, 3.8 mg / pill of PEG6000, 3.8 mg / pill of titanium dioxide, 15.2 mg / pill of talc, and 254 mg / pill of purified water.

2. The method for preparing Lansuo capsule according to claim 1, wherein: The preparation of the pellet cores with the main drug layer and the isolation layer comprises the following steps: Step 1: Prepare a 7.6% adhesive solution by mixing hydroxypropyl cellulose with purified water; Step 2: Evenly mix the main drug layer ingredients, lansoprazole, sucrose powder, corn starch, heavy magnesium carbonate, and low-substituted hydroxypropyl cellulose to obtain the main drug powder; evenly mix the heavy magnesium carbonate to obtain the isolation layer powder; Step 3: Use a centrifugal granulator to coat the main drug powder and the isolation layer powder on the surface of the sucrose pill core in sequence, control the granulation temperature at 28-34°C, the spray gun atomization pressure at 0.2-0.3 MPa, and the feeding oscillation frequency at 50-80 Hz. After drying, sieve to retain the pill cores with a main drug layer of 16-30 mesh and an isolation layer of 16-24 mesh.

3. The method for preparing Lansuo capsule according to claim 2, wherein: The main drug powder is coated twice: first, 2 / 3 of the main drug powder is coated, and the fine powder below 80 mesh is collected after drying and sieving, and then coated together with the remaining 1 / 3 of the main drug powder on the surface of the pill core.

4. The method for preparing Lansuo capsule according to claim 2, wherein: The isolation layer pellet core drying conditions are: drying in a vacuum drying oven at 40-45° C. until the moisture content is less than 3.0%, as measured by a rapid moisture drying instrument.

5. The method for preparing Lansuo capsule according to claim 1, wherein: The preparation of the enteric coating layer comprises the following steps: Step 1: dissolving PEG6000, titanium dioxide, and talc in purified water, and adding methacrylic acid-ethyl acrylate copolymer aqueous dispersion to prepare an enteric coating solution; Step 2: Use a fluidized bed coating machine to spray the enteric coating solution on the surface of the isolation layer pellets, control the inlet air temperature at 60°C, the material temperature at 31-35°C, and the spray gun atomization pressure at 0.2-0.3 MPa, dry until the moisture content is less than 3.0%, and then sieve to retain 16-24 mesh pellets.

6. The method for preparing Lansuo capsules according to claim 5, characterized in that: The amount of the enteric coating solution is prepared so that the weight of the isolation layer pellets increases by 25%.

7. The method for preparing Lansuo capsules according to any one of claims 1 to 6, characterized in that: The preheating conditions of the centrifugal granulator are: rotation speed 50-95R / M, air inlet speed 2000-3000R / M, air inlet temperature 50-70°C, exhaust speed 500-1000R / M, and the initial trigger temperature of the material temperature sensor is 37°C.

8. The method for preparing Lansuo capsule according to any one of claims 1 to 6, characterized in that: The preheating conditions of the fluidized bed coating machine are: fan frequency 40-50HZ, air inlet temperature 60°C, and initial trigger temperature of the material temperature sensor 38°C.

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