CN109364037B - Lafutidine tablet and preparation method thereof - Google Patents
Lafutidine tablet and preparation method thereof Download PDFInfo
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- CN109364037B CN109364037B CN201811510289.6A CN201811510289A CN109364037B CN 109364037 B CN109364037 B CN 109364037B CN 201811510289 A CN201811510289 A CN 201811510289A CN 109364037 B CN109364037 B CN 109364037B
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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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
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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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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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
- A61K9/2004—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
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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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
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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
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- 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 relates to the field of medicine preparation, and particularly relates to a lafutidine tablet and a preparation method thereof. The preparation method of the lafutidine tablet comprises the following steps: mixing the preprocessed lafutidine raw material with an adhesive, an internal disintegrating agent and a filler, and then carrying out fluidized drying; then mixing with external disintegrating agent and lubricant, tabletting and coating. Pretreated lafutidine raw material particle size range D10Is 1.015-2.16 um, D50Is 2.684-7.367 um, D90Is 4.325-52.8 um. By the preparation method, the prepared lafutidine tablets can be guaranteed to have good stability, the dissolution curve is similar to that of the original research, the energy consumption in the preparation process is low, the pollution is small, and the lafutidine tablets are green and environment-friendly.
Description
Technical Field
The invention relates to the field of medicine preparation, and particularly relates to a lafutidine tablet and a preparation method thereof.
Background
Lafutidine, chemically known as (+/mono) -2- [ (2-furylmethyl) sulfinyl ] N- [4- (phytyl piperidinyl methyl) -2-pyridinyl ] oxy- (Z) -2-butenyl ] acetamide, is a new generation of long-acting, potent H2-receptor antagonist, developed by Fuji and Roc pharmaceutical Co, Japan, mainly used for the treatment of gastric and duodenal ulcers. Research shows that lafutidine can continuously inhibit basic secretion and night secretion of gastric acid and pepsin of human body and secretion caused by stimulating factors such as tetrapeptide gastrin, and can resist gastric mucosa damage caused by various gastric stimulating factors. Lafutidine is widely cited in the form of tablets, but in the prior art, the Lafutidine tablets have the technical problems of poor stability and dissimilar dissolution curve with the original research.
Disclosure of Invention
The invention provides a preparation method of a lafutidine tablet, which can ensure that the lafutidine tablet prepared by the preparation method has good stability, the dissolution curve is similar to that of the lafutidine tablet prepared by the original research, and the energy consumption in the preparation process is low.
The invention provides a lafutidine tablet which is high in stability, uniform in content of main drugs, good in dissolution effect and low in toxic and side effects.
The invention is realized by the following steps:
a preparation method of lafutidine tablets comprises the following steps:
mixing the preprocessed lafutidine raw material with an adhesive, an internal disintegrating agent and a filler, and then carrying out fluidized drying; then mixing with an external disintegrating agent and a lubricant, and tabletting and coating; pretreated lafutidine raw material particle size range D101.015 to 2.16 μm, D50Is 2.684 to 7.367 μm, D90Is 4.325 to 52.8 μm.
A lafutidine tablet is prepared by the preparation method of the lafutidine tablet.
The invention has the beneficial effects that: according to the lafutidine tablet prepared by the invention, the lafutidine raw material is pretreated, the granularity of the lafutidine raw material is controlled, the raw material in the lafutidine tablet is prevented from being aggregated, the uniform content of the main drug is ensured, the dissolution effect is improved, the stability of the lafutidine tablet is improved, and the treatment effect of the lafutidine tablet is further improved. Simultaneously, change drying method, promote drying efficiency, and prevent among the prior art that the lafutidine tablet that long-time drying arouses is rotten, and prevent in the drying process granule caking, guarantee the quality of lafutidine tablet then. Further replacing the solution used in the preparation process of the tablet, ensuring the safety and the effectiveness of the preparation and realizing faster dissolution; and the preparation process is simple and is suitable for industrial mass production. And the whole preparation process has low energy consumption, little pollution and environmental protection.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The lafutidine tablet and the method for producing the same according to the embodiment of the present invention are specifically described below.
A preparation method of lafutidine tablets comprises the following steps:
s1, preprocessing a lafutidine raw material;
preprocessing the lafutidine raw material to ensure that D10 of the preprocessed lafutidine raw material is 1.015-2.16 mu m; d50 is 2.684-7.367 μm; d90 is 4.325-52.8 μm. The inventor finds that the lafutidine tablet has poor stability and poor dissolution effect, and the lafutidine raw material has large electrostatic action and is easy to agglomerate together, so that the main drug content is not uniform, the stability is affected, and the dissolution effect is poor. The inventor finds that the aggregation of the lafutidine raw material can be effectively controlled by controlling the particle size of the lafutidine raw material, and the prepared lafutidine tablet is ensured to have good stability and dissolution effect. If the number of the selected particles is too large during the screening, the particle size of the lafutidine raw material becomes smaller, resulting in a decrease in both dissolution effect and stability. On the other hand, if the selected mesh number is too low, the particle size of the raw material of lavetidine becomes too large, which also causes a decrease in dissolution effect and a decrease in stability.
Further, the pretreatment is to sieve, mechanically crush or micronize the raw material of lafutidine to obtain a particle size range D of lafutidine raw material101.015 to 2.16 μm, D50Is 2.684 to 7.367 μm, D90Is 4.325 to 52.8 μm. By adopting the method, the granularity of the lafutidine raw material can be effectively controlled, and the dissolution effect and stability of the lafutidine tablet are further ensured.
Furthermore, the dosage of the raw material of lafutidine accounts for 7-10% of the total mass of the lafutidine tablet, and the use of the raw material of lafutidine in the range can ensure the treatment effect of lafutidine tablet.
S2, preparing granules containing main medicine;
firstly, the adhesive raw material and water are mixed to form a mixed solution, namely the adhesive, and the adhesive raw material is prepared into the solution, so that the adhesive and other materials are more favorably and uniformly mixed, and the uniformity of the medicine is further ensured. Meanwhile, the solvent for dissolving the raw material of the adhesive is water instead of organic solvents such as ethanol and the like in the prior art, so that the solvent residue is reduced, the potential safety hazard of the medicine is reduced, and the pollution of the solvent to the environment is reduced.
Furthermore, the usage amount of the raw materials of the binder accounts for 2-5% of the total mass of the lafutidine tablet, the binder within the range can ensure the binding effect of the binder, and meanwhile, the usage amount of the auxiliary materials is controlled, so that the side effect of the lafutidine tablet is reduced. And the mass percentage concentration of the prepared adhesive is 5-10%.
Furthermore, the adhesive is hydroxypropyl cellulose, and the adhesive can be selected to ensure that the adhesive can effectively adhere various substances and ensure that auxiliary materials do not influence the drug effect of the drug.
Furthermore, the preprocessed lafutidine raw material is mixed with the filler and the internally added disintegrant to obtain a dry-mixed material, and the lafutidine raw material is mixed with the filler and the internally added disintegrant, so that the lafutidine raw material and various auxiliary materials are mixed uniformly, and the disintegration effect of the lafutidine tablet is ensured.
The dosage of the internal disintegrating agent is 60-70% of the total dosage of the internal disintegrating agent and the external disintegrating agent. The meaning of the internally added disintegrating agent is that the dosage of the disintegrating agent mixed with the filler and the raw material of lafutidine accounts for 60-70% of the dosage of the disintegrating agent of the whole tablet, and the internally added disintegrating agent is added to ensure the disintegrating effect of the tablet.
The total dosage of the internal disintegrating agent and the external disintegrating agent accounts for 5.0-9.0% of the total mass of the lafutidine tablet, and the internal disintegrating agent and the external disintegrating agent are the same substance, so that the stability of the medicine is ensured, and the toxic and side effects are reduced. Meanwhile, the internal disintegrating agent and the external disintegrating agent are all croscarmellose sodium, low-substituted hydroxypropyl cellulose or carboxymethyl starch sodium. The disintegrating agent can ensure the disintegrating effect of the tablet, and then ensure the treatment effect of the tablet.
Furthermore, the dosage of the filler accounts for 70-90% of the total material mass of the lafutidine tablet, and the filling agent in the proportion is more beneficial to tabletting to form a tablet with a stable structure.
Further, the filler is one or a combination of more of starch, lactose and microcrystalline cellulose; preferably corn starch, 200M lactose, microcrystalline cellulose pH 101. Microcrystalline cellulose pH101 is preferred as a filler because of its better particle size, which improves the uniformity of dispersion and thus the uniformity of the drug.
Further, the dry-mixed materials are mixed with a binding agent to form granules containing the main drug, specifically, the dry-mixed materials and the binding agent are mixed, stirred and sheared for 60-120 seconds to form granules, and then the granules are dried and granulated through 20-24 meshes. The granule has appropriate water content and uniform drug content.
The drying is fluidized drying, the fluidized bed is adopted for fluidized drying in the embodiment of the invention, the existing conventional oven drying is not adopted, the oven and the blower adopted in the prior art are used for drying, the drying efficiency is low, the particle size of the prepared particles is not uniform, and the active ingredients are not favorably dissolved out.
The conditions for fluidized bed drying were: the inlet air temperature is 70-80 ℃, and the inlet air volume is 1600-1800 m3and/H, the drying effect can be ensured by adopting the drying conditions, and the stability of the medicine is ensured. The water content of the dried granules containing the main drug is less than 4.0 percent.
S3, tabletting, coating and drying;
furthermore, the granules containing the main drug are mixed with a lubricant and an external disintegrating agent and then tabletted. When the granules containing the main drug are mixed with the lubricant and the external disintegrating agent, the mixing effect of the granules containing the main drug and the disintegrating agent is ensured, and the disintegrating performance of the finally prepared tablet is ensured.
Furthermore, the dosage of the lubricant is 2-4% of the total mass of the lafutidine tablet, the lubricant is a mixture obtained by mixing magnesium stearate and silicon dioxide according to the mass ratio of 1: 3-3: 1, and the effect of the lafutidine tablet can be ensured by adopting the mixture of magnesium stearate and silicon dioxide as the lubricant.
It should be noted that the mass of the total material mentioned in the examples of the present invention refers to the total mass of other materials that do not contain a solvent before coating.
The further mixing time is 5-10 minutes, so that the mixing effect of the granules containing the main drug, the disintegrating agent and the lubricant is ensured, and the stability and the dissolution effect of the drug are ensured.
The tabletting is carried out according to the theoretical tablet weight. Controlling the hardness to be 1.2kg/cm2～3.5kg/cm2The hardness is controlled within the range, so that the coating and transportation requirements can be met, and the requirement on tabletting equipment is low.
Coating the plain tablets after tabletting, specifically, the coating is to put the plain tablets into a coating pot, uniformly spray coating powder solution on the plain tablets under certain conditions, form a coating film on the surfaces of the plain tablets, rotate at the speed of 10 r/min, have the air inlet temperature of 70-80 ℃ and the air inlet amount of 250-300 m3/H。
Further, the coating powder solution is a mixed solution formed by mixing the coating powder with water. The coating powder is conventional coating powder in the prior art, such as Shanghai Kalekang coating technology Limited, film coating premix (gastric soluble)
(gastric solution) 03F 580004.
The weight of the coated tablet containing the main drug is increased by 6-10%, so that the coating effect and the stability of the tablet are ensured.
Further, the total amount of the solvent coating powder solution used in the embodiment of the invention is 40-60% of the total mass of the lafutidine tablet. The solvent in the above proportion can ensure the dispersion degree of each substance. The solvent in the volume of the embodiment of the present invention includes a solvent for dissolving the raw material of the binder in preparing the binder, a solvent for mixing with the coating powder in preparing the coating solution, and the like.
Further, the solvent is water, most preferably deionized or purified water. The embodiment of the invention adopts water as the solvent, avoids the residue of organic solvents such as ethanol and the like, avoids the crystal form transformation of the medicine, and reduces the toxic and side effects of the medicine.
The embodiment of the invention also provides a lafutidine tablet, which is prepared by the preparation method of lafutidine tablet.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
The embodiment provides a preparation method of lafutidine tablets, which comprises the following steps:
s1, preprocessing lafutidine raw material, namely, sieving the lafutidine raw material with a 120-mesh sieve by 50g, and preprocessing lafutidine raw material D10Is 2.16 μm, D507.367 μm, D90It was 52.8 μm.
S2, preparing granules containing main medicine;
23.40g of hydroxypropyl cellulose were dissolved in 444.6g of water to give a 5% strength by mass binder.
The sieved raw lafutidine material is mixed with 14.98g of corn starch, 319.64g of lactose, 125.39g of microcrystalline cellulose and 29.7g of croscarmellose sodium to obtain a dry-blended material. And then mixing the dry-mixed materials with the adhesive for 60 seconds, granulating, drying, and grading by a 24-mesh screen to obtain the granules containing the main drug. The drying adopts fluidized bed drying, and the drying conditions are as follows: the inlet air temperature is 80 ℃, and the inlet air volume is 1600m3And H, drying until the moisture content is less than 4.0 percent, and discharging.
S3, tabletting, coating and drying;
mixing granules containing main drug with 14.00g of magnesium stearate and 10.00g of silicon dioxide and 12.0g of croscarmellose sodium for 5 minutes, tabletting, placing the plain tablets in a coating pan, wherein the rotation speed of the coating pan is 10 r/min, the air inlet temperature is 75 ℃, and the air inlet amount is 300m3And H, uniformly spraying the coating powder solution on the plain tablets. Wherein the hardness of the tablet is 1.2kg/cm2(ii) a The coating powder solution was prepared by dissolving 90g (gastric soluble) 03F580004 in 810g of water; the weight of the coated tablet is increased by 6%.
The embodiment also provides a lafutidine tablet prepared by the method.
Examples 2 to 5
Examples 2-5 provide a process for preparing a delavirdine tablet that is substantially identical to the process for preparing a lafutidine tablet provided in example 1, except that the specific operating conditions of the process for preparing the lafutidine tablet provided in examples 2-5 are varied and the specific materials used are different.
Example 2
The pretreatment is micronization, and D of the particle size range of the preprocessed lafutidine raw material101.015 μm, D502.684 μm, D90The dosage of the raw material of the lafutidine is 4.325 mu m, and the dosage of the lafutidine raw material is 8.35 percent of the total mass of the lafutidine tablet.
The amount of hydroxypropyl cellulose was 2% by mass of the total material of the lafutidine tablet, and the binder was prepared to have a concentration of 5% by mass.
The internal disintegrating agent and the external disintegrating agent are carboxymethyl starch sodium, the dosage of the internal disintegrating agent accounts for 70% of the total dosage of the internal disintegrating agent and the external disintegrating agent, and the total dosage of the internal disintegrating agent and the external disintegrating agent accounts for 5.0% of the total mass of the lafutidine tablet.
The filler is 200M lactose, and the dosage of the lactose accounts for 82.15 percent of the total mass of the lafutidine tablet.
Stirring and shearing for 120S during granulation, and drying conditions are as follows: the inlet air temperature is 75 ℃, and the inlet air volume is 1700m3and/H, sieving the granules containing the main drug with a 24-mesh sieve to complete granules, wherein the water content of the granules containing the main drug is lower than 4%.
The mass ratio of magnesium stearate to silicon dioxide is 5.5:6.5, and the dosage of the lubricant is 2.5% of the total mass of the lafutidine tablet. The mixing time was 10 minutes, and the hardness was controlled to be 3.5kg/cm during tabletting2。
The weight of the coated tablet is increased by 10 percent, and the total amount of the solvent is 40 percent of the total mass of the lafutidine tablet.
Example 3
The pretreatment is mechanical crushing, and D of the grain size range of the preprocessed lafutidine raw material101.425 μm, D503.413 μm, D90The dosage of the raw material of the lafutidine is 7.497 mu m, and the dosage of the lafutidine raw material is 7 percent of the total mass of the lafutidine tablet.
The dosage of the hydroxypropyl cellulose accounts for 5 percent of the total mass of the lafutidine tablet, and the prepared adhesive has the mass percentage concentration of 10 percent.
The internal disintegrating agent and the external disintegrating agent are carboxymethyl starch sodium, the dosage of the internal disintegrating agent accounts for 60 percent of the total dosage of the internal disintegrating agent and the external disintegrating agent, and the total dosage of the internal disintegrating agent and the external disintegrating agent accounts for 9.0 percent of the total mass of the lafutidine tablet.
The filler is microcrystalline cellulose with pH101, and the dosage of the filler accounts for 70% of the total mass of the lafutidine tablet.
Stirring and shearing for 80S during granulation, wherein the drying conditions are as follows: the inlet air temperature is 75 ℃, and the inlet air volume is 1600m3and/H, sieving the granules containing the main drug with a 24-mesh sieve to complete granules, wherein the water content of the granules containing the main drug is lower than 4%.
The mass ratio of magnesium stearate to silicon dioxide is 1:2, and the dosage of the lubricant is 3% of the total mass of the lafutidine tablet. The mixing time was 8 minutes, and the tablet was compressed to a controlled hardness of 2.5kg/cm2。
The weight of the coated tablet is increased by 7 percent, and the total amount of the solvent is 60 percent of the total mass of the lafutidine tablet.
Example 4
The pretreatment is sieving, D of the grain size range of the preprocessed lafutidine raw material101.224 μm, D503.017 μm, D90The dosage of the raw material of the lafutidine is 6.983 mu m, and the dosage of the lafutidine raw material is 8 percent of the total mass of the lafutidine tablet.
The dosage of the hydroxypropyl cellulose accounts for 3 percent of the total mass of the lafutidine tablet, and the mass percentage concentration of the prepared adhesive is 8 percent.
The internal disintegrating agent and the external disintegrating agent are all croscarmellose sodium, the dosage of the internal disintegrating agent accounts for 65% of the total dosage of the internal disintegrating agent and the external disintegrating agent, and the total dosage of the internal disintegrating agent and the external disintegrating agent accounts for 7.0% of the total mass of the lafutidine tablet.
The filler is a mixture of corn starch, 200M lactose and microcrystalline cellulose with the pH value of 101, and the dosage of the filler accounts for 81.5 percent of the total mass of the lafutidine tablet.
Stirring scissors for softeningCutting for 100S, and drying under the conditions of: the inlet air temperature is 70 ℃, and the inlet air volume is 1650m3and/H, sieving the granules containing the main drug with a 24-mesh sieve to complete granules, wherein the water content of the granules containing the main drug is lower than 4%.
The mass ratio of magnesium stearate to silicon dioxide is 1:3, and the dosage of the lubricant is 3.5 of the total mass of the lafutidine tablet. The mixing time was 6 minutes, and the tablet was compressed while controlling the hardness to 1.5kg/cm2。
The weight of the coated tablet is increased by 8 percent, and the total amount of the solvent is 55 percent of the total mass of the lafutidine tablet.
Example 5
The pretreatment is sieving, D of the grain size range of the preprocessed lafutidine raw material101.73 μm, D506.109 μm, D90The dosage of the raw material of the lafutidine is 21.375 mu m, and the dosage of the lafutidine raw material is 9 percent of the total mass of the lafutidine tablet.
The amount of hydroxypropyl cellulose was 4% by mass of the total material of the lafutidine tablet, and the binder was prepared to have a concentration of 7% by mass.
The internal disintegrating agent and the external disintegrating agent are all croscarmellose sodium, the dosage of the internal disintegrating agent accounts for 68% of the total dosage of the internal disintegrating agent and the external disintegrating agent, and the total dosage of the internal disintegrating agent and the external disintegrating agent accounts for 6.5% of the total mass of the lafutidine tablet.
The filler is a mixture of corn starch, 200M lactose and microcrystalline cellulose with the pH value of 101, and the dosage of the filler accounts for 78.5 percent of the total mass of the lafutidine tablet.
Stirring and shearing 70S during granulation, and drying conditions are as follows: the inlet air temperature is 72 ℃, and the inlet air volume is 1650m3and/H, sieving the granules containing the main drug with a 24-mesh sieve to complete granules, wherein the water content of the granules containing the main drug is lower than 4%.
The mass ratio of magnesium stearate to silicon dioxide is 5:7, and the dosage of the lubricant is 2% of the total mass of the lafutidine tablet. The mixing time was 10 minutes, and the tablet was compressed to a controlled hardness of 3kg/cm2。
The weight of the coated tablet is increased by 9 percent, and the total amount of the solvent is 53 percent of the total mass of the lafutidine tablet.
Comparative example 1: lafutidine tablets were prepared according to the method provided in example 1, except that the Lafutidine starting material was sieved to 100 mesh.
Comparative example 2: lafutidine tablets were prepared according to the method provided in example 1, except that the Lafutidine starting material was sieved to 80 mesh.
Comparative example 3: lafutidine tablets were prepared according to the method provided in example 1, except that the drying mode was oven drying at 75 ℃.
The granularity of the treated lafutidine is shown in table 1, the dissolution rate in water of the lafutidine tablets of the original medicine, comparative examples 1 to 2 and examples 1 to 5 is detected, the detection method is shown in the general rule of the 4 th pharmacopoeia of China, and the specific detection result is shown in table 2.
Table 1 particle size data
| Screen mesh | D10/μm | D50/μm | D90/μm |
| 80 | 2.532 | 9.465 | 118.413 |
| 100 | 2.346 | 8.206 | 69.578 |
| 120 | 2.16 | 7.367 | 52.8 |
| 130 | 1.73 | 6.109 | 21.375 |
| 150 | 1.425 | 3.413 | 7.497 |
| 180 | 1.224 | 3.017 | 6.983 |
| 200 | 1.015 | 2.684 | 4.325 |
| Jet milling | 1.687 | 5.154 | 18.173 |
| Untreated | 2.636 | 8.857 | 306.192 |
TABLE 2 dissolution test results
As can be seen from table 2, the dissolution rate of the lafutidine tablet provided by the embodiment of the present invention is similar to that of the original research, but changing the sieving mesh number or the drying manner will cause the dissolution rate of the lafutidine tablet to change, which is not favorable for the dissolution of lafutidine.
The lafutidine tablets of examples 1 to 5 and comparative examples 1 to 3 were allowed to stand at a temperature of 40. + -. 2 ℃ and a relative humidity of RH 75. + -. 5% for 30 days, and then the dissolution thereof was measured, and the results of the measurements are shown in Table 3.
Dissolution in Water after 330 days in Table
As can be seen from table 3, accelerated testing showed that the examples had a dissolution profile similar to that of the original study and F2 was greater than 60, while the comparative examples remained dissimilar and the product stability was poor.
In conclusion, the lafutidine tablet prepared by the invention is prepared by screening lafutidine raw materials, controlling the granularity of the lafutidine raw materials, preventing the raw materials in the lafutidine tablet from aggregating, ensuring the uniform content of the main drug, improving the dissolution effect, improving the stability of the lafutidine tablet and further improving the treatment effect of the lafutidine tablet. Meanwhile, the drying mode is changed, the energy consumption is reduced, the drying effect is improved, the lafutidine tablet caused by long-time drying in the prior art is prevented from deteriorating, the tablet is prevented from being bonded in the drying process, and the quality of the lafutidine tablet is further ensured. Further replacing the solution used in the preparation process of the tablet, ensuring the safety and the effectiveness of the preparation and realizing faster dissolution; and the preparation process is simple and is suitable for industrial mass production.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A preparation method of lafutidine tablets is characterized by comprising the following steps:
mixing the preprocessed lafutidine raw material with an adhesive, an internal disintegrating agent and a filler, and then carrying out fluidized drying; then mixing with an external disintegrating agent and a lubricant, and tabletting and coating; pretreated lafutidine raw material particle size range D101.015 to 2.16 μm, D50Is 2.684 to 7.367 μm, D904.325-52.8 mu m, wherein the dosage of the binder raw material accounts for 2-5% of the total mass of the lafutidine tablet;
the conditions of fluidized drying were: the inlet air temperature is 70-80 ℃, and the inlet air volume is 1600-1800 m3/H；
The raw material of the adhesive is one of povidone K30, hydroxypropyl methylcellulose and hydroxypropyl cellulose; the filler is one or a combination of more of starch, lactose and microcrystalline cellulose; the internal disintegrating agent and the external disintegrating agent are all croscarmellose sodium, low-substituted hydroxypropyl cellulose or carboxymethyl starch sodium;
the using amount of the internal disintegrating agent is 60-70% of the total using amount of the internal disintegrating agent and the external disintegrating agent; the total dosage of the internal disintegrating agent and the external disintegrating agent accounts for 5.0-9.0% of the total mass of the lafutidine tablet.
2. A process for preparing lafutidine tablet according to claim 1, wherein the pretreatment is to screen, mechanically pulverize or micronize the lafutidine raw material to give lafutidine raw material a particle size range D101.015 to 2.16 μm, D50Is 2.684 to 7.367 μm, D90Is 4.325 to 52.8 μm.
3. A method for producing a lafutidine tablet according to claim 1, wherein the drying by fluidization after mixing is a main drug-containing granule obtained by mixing the lafutidine raw material subjected to pretreatment with the filler, the internal disintegrant, and the binder, stirring and shearing for 60 to 120 seconds to granulate, then drying by fluidization, and granulating through 20 to 24 mesh.
4. The method of manufacturing a lafutidine tablet according to claim 1 or 2, wherein the binder is a mixed solution formed by mixing a binder raw material and water.
5. A process for preparing lafutidine tablet according to claim 1,
the dosage of the lafutidine raw material accounts for 7-10% of the total mass of the lafutidine tablet.
6. The method for preparing lafutidine tablet according to claim 1, wherein the amount of the filler is 70 to 85% of the total mass of lafutidine tablet.
7. The method of claim 1, wherein the coating is performed by spraying the coating powder solution uniformly onto the surface of the tablet obtained after tableting to form a coating film.
8. A method for preparing lafutidine tablet according to claim 1, wherein the solvent used in the preparation of lafutidine tablet is 40 to 60% by mass of the total material of lafutidine tablet.
9. The method of preparing lafutidine tablet according to claim 8, wherein the solvent is purified water.
10. Lafutidine tablets, which are prepared by the method for preparing Lafutidine tablets according to any one of claims 1 to 9.
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