CN116440094A - Lansoprazole sustained-release tablet and preparation method thereof - Google Patents

Lansoprazole sustained-release tablet and preparation method thereof Download PDF

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Publication number
CN116440094A
CN116440094A CN202210008119.8A CN202210008119A CN116440094A CN 116440094 A CN116440094 A CN 116440094A CN 202210008119 A CN202210008119 A CN 202210008119A CN 116440094 A CN116440094 A CN 116440094A
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China
Prior art keywords
release
sustained
lansoprazole
parts
tablet
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Inventor
张贵民
张超
秦守刚
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Shandong New Time Pharmaceutical Co Ltd
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Shandong New Time Pharmaceutical Co Ltd
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Priority to CN202210008119.8A priority Critical patent/CN116440094A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Abstract

The invention provides a lansoprazole sustained-release tablet, which comprises a tablet core and a coating layer, wherein the tablet core comprises sustained-release particles, quick-release particles and other pharmaceutically acceptable auxiliary materials, and the coating layer is made of enteric-coated film coating powder. The lansoprazole sustained-release tablet provided by the invention can be used for rapidly taking effect and maintaining blood concentration after being orally taken, and has high bioavailability and small side effect; the solubility of lansoprazole is improved, and the solubilization by using a surfactant is not needed; has high stability to acid and does not need to be coated with a release coating. The lansoprazole sustained-release tablet adopts a secondary granulating mode and adopts dry granulating, sustained-release granules and quick-release granules are respectively prepared, the high-temperature drying process after the traditional wet granulating is avoided, and the stability of lansoprazole is improved.

Description

Lansoprazole sustained-release tablet and preparation method thereof
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a lansoprazole sustained-release tablet and a preparation method thereof.
Background
Lansoprazole is a new generation of proton pump inhibitor antiulcer drug following omeprazole, similar in structure to omeprazole, and is superior to omeprazole in chemical stability and therapeutic action due to the introduction of fluorine atoms. Lansoprazole was developed by the martial arts pharmaceutical company of japan in 1994 and was first marketed in france. China began to be applied to clinic in 1998.
Lansoprazole is white to brown tasteless crystalline powder, has very small water solubility, is unstable under acidic conditions, is very easily damaged in gastric acid, is relatively slow to be orally absorbed after being prepared into common tablets or capsules, has relatively low bioavailability and relatively poor stability, and seriously influences the clinical curative effect of the medicine. The research also finds that lansoprazole is unstable to humidity, heat and illumination, is extremely easy to degrade and oxidize, generates inactive impurities, reduces the content of main drugs, and causes allergic reaction of users. In order to solve the problem that lansoprazole is unstable in gastric acid, in the prior art, the lansoprazole is usually prepared into enteric tablets or prepared into enteric granules and then filled into capsules, and the stability of the lansoprazole is influenced because a coating liquid is acidic, and a layer of barrier coating is usually added between a tablet core/pill core and the enteric coating to improve the stability of the preparation, but the preparation process of the barrier coating is complex, and the production cost is higher; meanwhile, a solubilizer such as sodium dodecyl sulfate is usually added in the prior art to solve the problem of dissolution, but the dissolution of the tablet by the solubilizer is limited, and the stability of the compatibility of sodium dodecyl sulfate and lansoprazole is poor, so that the stability of the lansoprazole medicine can be influenced.
In addition, patent CN109692161a discloses a lansoprazole sustained-release preparation, which consists of a tablet core prescription and a coating layer prescription, wherein the tablet core consists of lansoprazole, lactose, hydroxypropyl methylcellulose, crospovidone, talcum powder and magnesium stearate, and the coating layer prescription consists of two or more than two of ethylcellulose, hydroxypropyl methylcellulose, polyacrylic resin, microcrystalline cellulose and magnesium stearate, but the sustained-release preparation is hardly dissolved in 2 hours, the drug has slow onset, low bioavailability and poor stability; patent CN104013580B discloses a lansoprazole sustained-release pellet, which maintains the stability of lansoprazole by adding an antioxidant, and avoids the damage of high temperature to lansoprazole by spray drying granulation and spray coating, and the preparation process needs to be strictly controlled.
Although various enteric coated tablets or capsules related to lansoprazole have been disclosed in the prior art, how to obtain lansoprazole tablets with high stability, simple preparation process, quick effect and high bioavailability is still an important research topic of researchers.
Disclosure of Invention
In view of the above, the invention aims to provide a lansoprazole enteric-coated tablet with high stability, simple preparation process, quick response and high bioavailability and a preparation method thereof.
In order to achieve the above purpose, the present invention provides the following technical solutions:
the lansoprazole sustained-release tablet comprises a tablet core and a coating layer, wherein the tablet core comprises sustained-release particles, quick-release particles and other pharmaceutically acceptable auxiliary materials, and the coating layer is made of enteric film coating powder.
Preferably, the slow release particles in the tablet core comprise lansoprazole, sucrose powder, magnesium hydroxide, and hydroxypropyl methylcellulose.
Preferably, the immediate release particles in the tablet core comprise lansoprazole, sucrose powder, magnesium hydroxide, and croscarmellose sodium.
Preferably, the slow release particles in the tablet core comprise 15-20 parts of lansoprazole, 10-30 parts of sucrose powder, 30-45 parts of magnesium hydroxide and 180-220 parts of hydroxypropyl methylcellulose;
further preferably, the sustained-release particles in the tablet core comprise 15-20 parts of lansoprazole, 15-25 parts of sucrose powder, 35-40 parts of magnesium hydroxide and 200-220 parts of hydroxypropyl methylcellulose.
Preferably, the tablet core immediate release particles comprise 10-15 parts of lansoprazole, 15-30 parts of sucrose powder, 20-30 parts of magnesium hydroxide and 2-5 parts of crosslinked sodium carboxymethylcellulose;
further preferably, the immediate release granule in the tablet core comprises 10-15 parts of lansoprazole, 20-25 parts of sucrose powder, 25 parts of magnesium hydroxide and 3 parts of croscarmellose sodium.
In some embodiments, the slow release particles comprise 15 parts lansoprazole and the immediate release particles comprise 15 parts lansoprazole.
In some embodiments, the slow release particles comprise 20 parts lansoprazole and the immediate release particles comprise 10 parts lansoprazole.
Preferably, the other pharmaceutically acceptable excipients include disintegrants, lubricants and glidants; the disintegrating agent is selected from one of croscarmellose sodium, sodium carboxymethyl starch, crospovidone, low-substituted hydroxypropyl cellulose and calcium carboxymethyl cellulose, and is more preferably croscarmellose sodium; the lubricant is selected from one of stearic acid, magnesium stearate, sodium stearyl fumarate, polyethylene glycol 4000 and polyethylene glycol 6000, and is more preferably magnesium stearate; the glidant is selected from one of colloidal silicon dioxide and talcum powder, and is more preferably colloidal silicon dioxide.
Preferably, the disintegrant is used in an amount of 5 to 10 parts by weight.
Preferably, the lubricant is used in an amount of 3 to 5 parts by weight.
Preferably, the glidant is used in an amount of 1-2 parts by weight.
Preferably, the lansoprazole tablet provided by the invention is dissolved in phosphate buffer with pH of 6.8 for 0.5h to 25-40%,1h to 45-60%,1.5h to 60-75%,4h to 90-97%, and 5h to more than or equal to 95%.
The preparation method of the lansoprazole sustained-release tablet adopts a secondary granulating mode and adopts dry granulating, sustained-release granules and quick-release granules are respectively prepared, after the granulating is finished, the sustained-release granules, the quick-release granules and other pharmaceutically acceptable auxiliary materials are taken, and tabletting is carried out after uniform mixing, so as to obtain tablet cores; and taking the tablet core to cover the enteric coating to obtain the lansoprazole sustained-release tablet.
Preferably, the preparation method of the slow release granule comprises the following steps: weighing lansoprazole, sucrose powder and magnesium hydroxide with the prescribed amounts, crushing, sieving, mixing and performing first dry granulation; pulverizing the prepared granule again, sieving, mixing with hydroxypropyl methylcellulose, and granulating by dry method for the second time to obtain sustained release granule.
Preferably, the preparation method of the quick release granule comprises the following steps: weighing lansoprazole, sucrose powder and magnesium hydroxide with the prescribed amounts, crushing, sieving, mixing and performing first dry granulation; pulverizing the prepared granule again, sieving, mixing with croscarmellose sodium, and granulating by dry method for the second time to obtain quick release granule.
Preferably, the preparation method of the lansoprazole sustained-release tablet comprises the following steps:
1) Preparation of slow-release particles: weighing lansoprazole, sucrose powder and magnesium hydroxide, crushing, sieving, uniformly mixing, performing first dry granulation by using a dry granulator, crushing and sieving the prepared granules again, uniformly mixing the granules with hydroxypropyl methylcellulose, performing second dry granulation by using the dry granulator, and sieving for later use after granulating;
2) Preparation of quick release particles: weighing lansoprazole, sucrose powder and magnesium hydroxide, crushing and sieving, uniformly mixing, granulating for the first time by using a dry granulator, crushing and sieving the prepared granules again, adding sodium carboxymethyl cellulose, uniformly mixing, granulating for the second time by using the dry granulator, and sieving for later use after granulating is completed;
3) Preparation of tablet cores: uniformly mixing the slow release particles, the quick release particles and other pharmaceutically acceptable auxiliary materials prepared in the step 1) and the step 2), and tabletting to obtain tablet cores;
4) Preparation of enteric coating: and adding the enteric film coating powder into a solvent, and coating the tablet core to obtain the lansoprazole sustained-release tablet.
Preferably, the enteric film coating material in step 4) is selected from the group consisting ofL100、/>L100-55、/>One of L30D-55.
Preferably, the solvent for dissolving the enteric film coating material in the step 4) is 70% ethanol.
Preferably, the weight gain percentage of the coating after the enteric coating in the step 4) is 3-4%.
Overall, the lansoprazole sustained-release tablet prepared by the invention has the following characteristic advantages compared with the prior art:
(1) Has high stability to acid, does not need to be coated with isolation coating, and has simple process.
(2) By adopting the mode of combining the slow release particles and the quick release particles, the oral administration can quickly take effect and maintain the blood concentration, and has high bioavailability and small side effect.
(3) The solubility of lansoprazole is improved without the use of a surfactant for solubilization.
(4) The secondary granulation mode is adopted, and the dry granulation is adopted, so that the high-temperature drying process after the traditional wet granulation is avoided, and the stability of lansoprazole is improved.
Detailed Description
The invention is further illustrated by the following examples, with the understanding that: the examples of the present invention are intended to be illustrative of the invention and not limiting thereof, so that simple modifications of the invention based on the method of the invention are within the scope of the invention as claimed.
The raw materials used in the invention can be purchased from the market, and the sucrose powder used in the invention is sucrose (C) 12 H 22 O 11 ) Mixing with corn starch, pulverizing into fine powder, and containing sucrose not less than 95.0%.
Example 1
Prescription: table 1 below.
Table 1:
the preparation method comprises the following steps:
1) Taking 20g of lansoprazole, 25g of sucrose powder and 40g of magnesium hydroxide, crushing, sieving, mixing and performing first dry granulation; pulverizing and sieving the prepared particles again, adding the particles and 200g HPMC into a mixer for full mixing, carrying out dry granulation for the second time after mixing, and sieving to obtain lansoprazole sustained release particles;
2) Taking 10g of lansoprazole, 25g of sucrose powder and 25g of magnesium hydroxide, crushing, sieving, mixing and performing first dry granulation; pulverizing and sieving the prepared particles again, adding the particles and 3g of crosslinked sodium carboxymethyl cellulose into a mixer for full mixing, carrying out secondary dry granulation after mixing, and sieving to obtain lansoprazole immediate release particles;
3) Adding 7g of crosslinked sodium carboxymethyl cellulose, 1.8g of colloidal silicon dioxide, lansoprazole sustained-release particles prepared in the step 1) and the step 2) and quick-release particles into a mixer, fully mixing, adding 3.2g of magnesium stearate, mixing, and tabletting 1000 tablets;
4) 15g of Eudragit enteric coating powder is taken, added into 187.5g of 70% ethanol and stirred for 45min, the tablet cores prepared above are coated by a coating machine, the coating weight is increased by 3%, and the lansoprazole enteric coating tablet is obtained after drying.
Example 2
Prescription: table 2 below.
Table 2:
the preparation method comprises the following steps: the same as in example 1.
Example 3
Prescription: table 3 below.
Table 3:
the preparation method comprises the following steps: the same as in example 1.
Example 4
Prescription: table 4 below.
Table 4:
the preparation method comprises the following steps: the same as in example 1.
Example 5
Prescription: table 5 below.
Table 5:
the preparation method comprises the following steps: the same as in example 1.
Example 6
Prescription: table 6 below.
Table 6:
the preparation method comprises the following steps: the same as in example 1.
Example 7
Prescription: table 7 below.
Table 7:
the preparation method comprises the following steps: the same as in example 1.
Example 8
Prescription: table 8 below.
Table 8:
the preparation method comprises the following steps: the same as in example 1.
Example 9
Prescription: table 9 below.
Table 9:
the preparation method comprises the following steps: the same as in example 1.
Example 10
Prescription: the same as in example 1.
The preparation method comprises the following steps:
1) Weighing prescription amount of lansoprazole, sucrose powder, magnesium hydroxide and hydroxypropyl methylcellulose, adding into a mixer, fully mixing, granulating by using a dry granulator, and sieving to obtain lansoprazole sustained-release particles;
2) Weighing prescription amount of lansoprazole, sucrose powder, magnesium hydroxide and croscarmellose sodium, adding into a mixer, fully mixing, granulating by using a dry granulator, and sieving to obtain lansoprazole quick-release granules;
3) Weighing prescribed amounts of croscarmellose sodium, colloidal silicon dioxide, lansoprazole sustained-release particles prepared in step 1) and step (2), adding the particles and quick-release particles into a mixer, fully mixing, adding magnesium stearate, mixing, and tabletting;
4) 15g of Eudragit enteric coating powder is taken, added into 187.5g of 70% ethanol and stirred for 45min, the tablet cores prepared above are coated by a coating machine, the coating weight is increased by 3%, and the lansoprazole enteric coating tablet is obtained after drying.
Comparative example 1
Prescription: table 10 below.
Table 10:
the preparation method comprises the following steps: the same as in example 1.
Comparative example 2
Prescription: table 11 below.
Table 11:
the preparation method comprises the following steps: the same as in example 1.
Comparative example 3
Prescription: table 12 below.
Table 12:
/>
the preparation method comprises the following steps:
1) Pulverizing and sieving lansoprazole, sucrose powder and magnesium hydroxide with a prescription amount, mixing, and performing first dry granulation; pulverizing the prepared granule again, sieving, adding into mixer together with 200g HPMC, mixing, granulating by dry method for the second time, and sieving;
2) Adding the prescription amount of the crosslinked sodium carboxymethyl cellulose, the colloidal silicon dioxide and the particles prepared in the step 1) into a mixer, fully mixing, adding magnesium stearate, mixing, and tabletting to 1000 tablets;
3) 15g of Eudragit enteric coating powder is taken, added into 187.5g of 70% ethanol and stirred for 45min, the tablet cores prepared above are coated by a coating machine, the coating weight is increased by 3%, and the lansoprazole enteric coating tablet is obtained after drying.
Comparative example 4
Prescription: table 13 below.
Table 13:
the preparation method comprises the following steps:
1. and (3) preparing tablet cores, namely weighing a proper amount of lansoprazole powder, adding auxiliary materials in the table, sieving with a 20-mesh sieve to prepare wet granules, drying at 50 ℃, sieving the dry granules with a 15-mesh sieve, finishing the granules, adding 1% magnesium stearate, uniformly mixing, and tabletting to obtain the tablet cores.
2. The preparation of the coating layer comprises mixing the auxiliary materials, sieving with 20 mesh sieve to obtain wet granule, drying at 50deg.C, sieving with 20 mesh sieve, grading, adding 1% magnesium stearate, and mixing to obtain the final product.
3. Press coating, namely weighing the coating materials with the prescription amount, and dividing the coating materials into 2 parts with the ratio of 1:1. Filling a part of coating material into a die, placing a tablet core in the middle of the upper surface of the coating material, filling the rest 1 part of coating material into the die, and tabletting again to obtain the required sustained-release tablet. Each tablet contains 20mg of lansoprazole.
Comparative example 5
Prescription: table 14 below.
Table 14:
the preparation method comprises the following steps:
1) Preparation of slow-release particles: mixing lansoprazole with hypromellose and xanthan gum, stirring to obtain a uniform mixture, and extruding the mixture into sheet or block; crushing the flaky or blocky matters to enable the flaky or blocky matters to completely pass through a second sieve of Chinese pharmacopoeia; adding microcrystalline cellulose and magnesium stearate into the sieved particles, and uniformly stirring to prepare a slow-release layer mixture;
2) Preparation of quick release particles: adding lansoprazole into crospovidone and microcrystalline cellulose, stirring to obtain a uniform mixture, and extruding the mixture into sheets or blocks; crushing the flaky or blocky matters to enable the flaky or blocky matters to completely pass through a second sieve of Chinese pharmacopoeia; adding magnesium stearate into the sieved particles, and uniformly stirring to prepare a quick-release layer mixture;
3) Pressing the quick release layer mixture and the slow release layer mixture into double-layer tablets by using a double-layer tablet press;
4) The prepared medicine is coated by a coating machine, and the weight of the coating is increased by 3%.
Verification embodiment
1. Stability test
The lansoprazole sustained-release preparations prepared in examples 1 to 10 and comparative examples 1 to 5, and commercially available lansoprazole enteric-coated capsules were packaged with self-sealing bags. The experimental conditions are as follows: the temperature is 40+/-2 ℃ and the humidity is 75+/-5%. Samples were taken at 0, 3 and 6 months, the enteric coating was removed to observe the core color or pellet color, and the content and the related results were measured, respectively, as shown in Table 15 below.
Table 15: accelerated stability test results
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From the results, the lansoprazole enteric-coated preparation prepared by the invention has good stability within 6 months under the condition of accelerating experiments, has no change in appearance, basically has no change in content, and basically has no change in related substances.
Dissolution test in phosphate buffer at pH6.8
Taking lansoprazole preparation prepared in examples 1-10 and comparative examples 1-5 as test group objects, measuring according to a dissolution rate and a release rate measuring method (the first method 2 of the four general rules 0931 of Chinese pharmacopoeia), taking 1000ml of hydrochloric acid solution as a dissolution medium, taking the rotating basket as a dissolution medium, rotating the rotating basket at 100 revolutions per minute, operating according to the law, immediately lifting the rotating basket out of the liquid level after 120 minutes, discarding the hydrochloric acid solution, immediately adding 1000ml of phosphate buffer solution with pH of 6.8 preheated to 37 ℃ and keeping the rotating speed unchanged, continuing the normal operation, removing solution and filtering, precisely measuring 5ml of continuous filtrate, precisely adding 1ml of sodium hydroxide solution with 0.15mol/L and shaking uniformly to serve as a test sample solution after 30, 60, 90, 120, 150, 180, 240 and 300 minutes; in addition, precisely weighing lansoprazole reference substance (Chinese food and drug inspection institute, batch No. 100709-200902, purity 99.8%) about 15mg, placing into a 100ml measuring flask, adding methanol to dissolve and dilute to scale, shaking up, precisely weighing 5ml, placing into a 25ml measuring flask, diluting to scale with phosphate buffer solution, shaking up; precisely weighing 5ml, precisely adding 1ml of 0.15mol/L sodium hydroxide solution, and shaking uniformly to obtain reference solution. Removing the test solution and the reference solution, and calculating the dissolution rate of the preparation at 30, 60, 90, 120, 150, 180, 240 and 300 minutes according to the method under the content measurement item. The dissolution results are shown in table 16 below.
Table 16 dissolution of lansoprazole sustained release formulations at various time points in phosphate buffer ph6.8
Test sample 30min 60min 90min 120min 150min 180min 240min 300min
Example 1 30.4 55.6 63.5 71.0 79.2 88.5 94.3 99.8
Example 2 38.2 58.6 68.0 76.8 83.1 87.6 96.8 99.0
Example 3 25.6 46.8 57.9 68.8 78.6 89.7 95.4 100.1
Example 4 39.5 59.7 67.5 74.3 82.6 85.4 94.9 99.2
Example 5 31.5 53.6 65.7 73.2 80.5 87.6 93.4 98.8
Example 6 38.9 61.6 73.6 81.7 87.9 93.2 96.7 99.9
Example 7 18.7 36.8 42.5 55.5 70.0 78.3 86.9 93.6
Example 8 34.5 64.0 79.6 88.1 92.8 98.0 98.9 97.6
Example 9 17.8 30.7 40.2 53.9 64.8 73.5 81.1 89.0
Example 10 23.4 36.7 47.5 63.8 72.6 80.0 88.2 93.5
Comparative example 1 25.1 39.0 48.7 56.6 64.8 73.9 85.4 89.3
Comparative example 2 22.9 37.9 46.1 53.9 63.0 71.2 83.5 86.8
Comparative example 3 17.9 23.5 29.8 37.6 52.9 68.1 72.8 76.7
Comparative example 4 0 2.8 4.7 7.6 65.9 98.7 98.6 ——
Comparative example 5 8.9 18.0 21.5 30.8 43.2 57.5 62.6 65.4
3. Bioavailability experiments
Lansoprazole preparations prepared in examples 1 to 10 and comparative examples 1 to 5 are used as test samples, and ordinary grade Beagle dogs are used as experimental animals according to a cross administration design. The reference preparation is commercial lansoprazole enteric capsule @ and the reference preparation is commercial lansoprazole enteric capsule @30 mg/tablet). When in administration, the mouth of a dog is broken off, a self-made preparation/reference preparation is stuffed into the throat of the dog, 10mL of purified water is poured, and the time is counted after the dog swallows. About 0.2mL of blood samples were collected at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48 and 72 hours before and after administration, respectively, and placed in heparinized centrifuge tubes, centrifuged at 4000g for 10min, and the supernatant was taken and frozen at-80℃for use. The collecting time error of the blood sampling points within 1h is +/-2 min, and the collecting error of the blood sampling points within 1 h-24 h is +/-10 min. The blood sampling time error of 24 hours and above is +/-1 hour. The time from the collection of blood to the centrifugation is built in ice. And a developed UPLC-MS/MS method is adopted to determine the lansoprazole content in the canine plasma. The pharmacokinetic parameters of lansoprazole in the plasma were calculated after oral administration of lansoprazole formulation to dogs using DAS2.1.1 drug-data processing software. The blood sampling time and the expected time are not coincident, and the drug generation parameter calculation is performed according to the actual blood sampling time, and the result is shown in table 17.
Table 17 relative bioavailability of lansoprazole sustained release formulations
Group of Cmax(μg/ml) Relative bioavailability (%)
Example 1 0.688±0.254 167.1±18.6
Example 2 0.735±0.236 159.5±17.3
Example 3 0.697±0.259 147.4±18.5
Example 4 0.437±0.266 138.6±19.2
Example 5 0.303±0.198 152.9±12.3
Example 6 0.721±0.202 118.6±14.5
Example 7 0.367±0.231 104.4±14.3
Example 8 0.876±0.128 114.9±14.3
Example 9 0.384±0.187 103.8±11.3
Example 10 0.358±0.245 112.5±15.6
Comparative example 1 0.547±0.226 81.5±12.3
Comparative example 2 0.479±0.141 76.9±16.8
Comparative example 3 0.237±0.135 85.6±15.4
Comparative example 4 0.334±0.251 67.4±14.9
Comparative example 5 0.279±143 60.0±15.8

Claims (10)

1. The lansoprazole sustained-release tablet is characterized by comprising a tablet core and a coating layer, wherein the tablet core comprises sustained-release particles, quick-release particles and other pharmaceutically acceptable auxiliary materials, and the coating layer is made of enteric film coating powder.
2. The sustained release tablet of claim 1, wherein the sustained release particles in the tablet core comprise lansoprazole, sucrose powder, magnesium hydroxide, hydroxypropyl methylcellulose.
3. The sustained-release tablet according to claim 1, wherein the immediate-release particles in the tablet core comprise lansoprazole, sucrose powder, magnesium hydroxide, and croscarmellose sodium.
4. The sustained-release tablet according to claim 1, wherein the sustained-release particles comprise 15 to 20 parts by weight of lansoprazole, 10 to 30 parts by weight of sucrose powder, 30 to 45 parts by weight of magnesium hydroxide, and 180 to 220 parts by weight of hydroxypropyl methylcellulose.
5. The sustained-release tablet according to claim 1, wherein the immediate-release particles comprise, in parts by weight, 10-15 parts of lansoprazole, 15-30 parts of sucrose powder, 20-30 parts of magnesium hydroxide, and 2-5 parts of croscarmellose sodium.
6. A sustained release tablet according to claim 1, wherein the other pharmaceutically acceptable excipients include disintegrants, lubricants and glidants.
7. The sustained-release tablet according to claim 6, wherein the disintegrant is used in an amount of 5 to 10 parts by weight, the lubricant is used in an amount of 3 to 5 parts by weight, and the glidant is used in an amount of 1 to 2 parts by weight.
8. A method for preparing a lansoprazole sustained-release tablet as claimed in any one of claims 1 to 7, characterized in that a secondary granulation mode is adopted, and dry granulation is adopted, sustained-release granules and quick-release granules are respectively prepared, after the granulation is completed, the sustained-release granules, the quick-release granules and other pharmaceutically acceptable auxiliary materials are taken, and tabletting is carried out after uniform mixing, so as to obtain tablet cores; and taking the tablet core to cover the enteric coating to obtain the lansoprazole sustained-release tablet.
9. The method of preparing a sustained release tablet according to claim 8, wherein the method of preparing the sustained release granule comprises the steps of: weighing lansoprazole, sucrose powder and magnesium hydroxide, crushing, sieving, mixing, and performing first dry granulation; pulverizing the prepared granule again, sieving, mixing with hydroxypropyl methylcellulose, and granulating by dry method for the second time to obtain sustained release granule.
10. The method of preparing a sustained release tablet according to claim 8, wherein the method of preparing the immediate release granule comprises the following steps: weighing lansoprazole, sucrose powder and magnesium hydroxide with the prescribed amounts, crushing, sieving, mixing and performing first dry granulation; pulverizing the prepared granule again, sieving, mixing with croscarmellose sodium, and granulating by dry method for the second time to obtain quick release granule.
CN202210008119.8A 2022-01-06 2022-01-06 Lansoprazole sustained-release tablet and preparation method thereof Pending CN116440094A (en)

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