CN111202718A - Ranitidine hydrochloride capsule and preparation method thereof - Google Patents
Ranitidine hydrochloride capsule and preparation method thereof Download PDFInfo
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- CN111202718A CN111202718A CN202010114924.XA CN202010114924A CN111202718A CN 111202718 A CN111202718 A CN 111202718A CN 202010114924 A CN202010114924 A CN 202010114924A CN 111202718 A CN111202718 A CN 111202718A
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- ranitidine hydrochloride
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- magnesium stearate
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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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 belongs to the field of medicines, and particularly relates to a ranitidine hydrochloride capsule and a preparation method thereof, wherein the ranitidine hydrochloride capsule comprises the following components in percentage by mass based on 100% of the total mass of the ranitidine hydrochloride capsule: 90-100% of ranitidine hydrochloride; 1-10% of microcrystalline cellulose; 1-10% of carboxymethyl starch sodium; 0.5 to 5 percent of magnesium stearate. The invention develops a new formula, adopts a mode of adding magnesium stearate partially, overcomes the defects of poor material fluidity and easy adhesion, ensures good stability of the capsule by strictly controlling the moisture of the granules through drying in a fluidized bed, and is suitable for large-scale production of ranitidine hydrochloride capsules.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a ranitidine hydrochloride capsule and a preparation method thereof.
Background
Ranitidine is currently the most widely used drug for the treatment of ulcers, developed by glaxo, a company of gelanin (glaxo) in the united kingdom. The traditional Chinese medicine composition is mainly used for treating hyperchlorhydria, heartburn, duodenal ulcer, benign gastric ulcer, postoperative ulcer, reflux esophagitis, Zollinger-Ellison syndrome and the like clinically, and can be used for treating upper gastrointestinal hemorrhage by intravenous injection. In the production of medicines, capsules are prepared by filling medicine powder or granules into empty capsules, can cover up peculiar smell and irritation of medicines, are convenient to swallow, and can prevent the medicines from being affected with damp, visible light and oxidation to a certain extent so as to stabilize the medicines. Ranitidine hydrochloride is white or yellow crystalline powder, and has poor fluidity, instability to damp and heat, extremely easy deliquescence, hygroscopicity and strict requirements on environment temperature and humidity, so that the process operability in the preparation process is poor. The product is unstable when the ranitidine is exposed to high temperature and high humidity for a long time, so that the increase of impurities and the coloring and yellowing of materials are easily caused, and the product quality is influenced. Therefore, the ranitidine hydrochloride raw material medicine is generally granulated, and filled after the powder chemical property of the ranitidine hydrochloride raw material medicine is improved.
The existing preparation method of the ranitidine capsule preparation can not completely avoid the phenomena of instability, moisture induction and the like of the ranitidine hydrochloride in the preparation method of the capsule preparation. The phenomenon of adhesion with equipment is easy to occur in the granulation preparation process, and the process is more, the equipment is more, the period of each process is longer, and the product stability is not facilitated. Therefore, there is a need for developing a process for preparing a ranitidine capsule preparation which can prepare a ranitidine capsule preparation with good stability and is suitable for industrial amplification.
Disclosure of Invention
The invention aims to overcome the defects in the prior art, provides a ranitidine hydrochloride capsule and a preparation method thereof, and aims to overcome the defects of instability, poor material flowability and easiness in adhesion of a product.
In order to achieve the purpose, the invention adopts the following technical scheme:
on one hand, the invention provides a ranitidine hydrochloride capsule, which comprises the following components in percentage by mass based on 100% of the total mass of the ranitidine hydrochloride capsule:
in one embodiment, the ranitidine hydrochloride capsule comprises the following components in percentage by mass based on 100% of the total mass of the ranitidine hydrochloride capsule:
or, the ranitidine hydrochloride capsule comprises the following components in percentage by mass:
or, the ranitidine hydrochloride capsule comprises the following components in percentage by mass:
on the other hand, the invention also provides a preparation method of the ranitidine hydrochloride capsule, which comprises the following steps:
firstly, ranitidine hydrochloride passes through a first screen to obtain ranitidine hydrochloride meeting the requirement of the particle size;
respectively sieving the microcrystalline cellulose and the carboxymethyl starch sodium by using a sieve to obtain the microcrystalline cellulose and the carboxymethyl starch sodium which meet the requirement of the particle size;
weighing the ranitidine hydrochloride, the microcrystalline cellulose, the sodium carboxymethyl starch and the magnesium stearate with the first mass which meet the requirement of the particle size according to the prescription amount to obtain raw and auxiliary materials;
adding the raw and auxiliary materials into a wet granulator, mixing, adding purified water, and granulating to obtain a soft material;
granulating the soft material by using a second screen, and drying by using a fluidized bed to obtain first dry particles;
vibrating the first dry particles, and then finishing the particles through a third screen to obtain second dry particles;
weighing a second mass of magnesium stearate, adding the second mass of magnesium stearate and the second dry granules, and uniformly mixing in a three-dimensional mixer to obtain target granules;
and filling the target particles to obtain the ranitidine hydrochloride capsule.
In one embodiment, the first mass is 0.3-3% based on 100% of the total mass of the ranitidine hydrochloride capsule;
and/or the second mass is 0.2-2%.
In one embodiment, the first screen has a mesh number of 60-100;
and/or the mesh number of the second screen is 16-20;
and/or the mesh number of the third screen is 30.
In one embodiment, the raw and auxiliary materials are added into a wet granulator to be mixed, and purified water is added for granulation to obtain a soft material, wherein the mixing time is 5-10 min.
In one embodiment, the drying process with a fluidized bed is carried out while controlling the moisture content in the granules to be less than 0.5% by mass.
In one embodiment, the fan frequency is 10-30Hz during the drying process with the fluidized bed.
In one embodiment, the material temperature is 30-40 ℃ in the process of drying by the fluidized bed;
and/or the temperature of the inlet air is 50-70 ℃.
In one embodiment, the step of weighing a second mass of magnesium stearate, adding the second mass of magnesium stearate and the second dry granules, and uniformly mixing in a three-dimensional mixer to obtain the target granules takes 10-30 min.
Aiming at the problems of instability, poor material fluidity and easy adhesion of the product, the invention develops a new formula, adopts a mode of adding magnesium stearate into the capsule, overcomes the defects of poor material fluidity and easy adhesion, strictly controls the moisture of the granules by drying in a fluidized bed, ensures the good stability of the capsule, and is suitable for large-scale production of ranitidine hydrochloride capsules.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects to be solved by the present invention more clearly apparent, the present invention is further described in detail below with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
On one hand, the invention provides a ranitidine hydrochloride capsule, which comprises the following components in percentage by mass based on 100% of the total mass of the ranitidine hydrochloride capsule:
further, the ranitidine hydrochloride capsule comprises the following components in percentage by mass based on 100% of the total mass of the ranitidine hydrochloride capsule:
or, the ranitidine hydrochloride capsule comprises the following components in percentage by mass:
or, the ranitidine hydrochloride capsule comprises the following components in percentage by mass:
wherein the microcrystalline cellulose acts as a filler; the sodium carboxymethyl starch plays a role of a disintegrating agent; magnesium stearate acts as a lubricant.
On the other hand, the invention also provides a preparation method of the ranitidine hydrochloride capsule, which comprises the following steps:
step S10, first screening ranitidine hydrochloride through a first screen to obtain ranitidine hydrochloride meeting the requirement of particle size;
step S20, respectively screening the microcrystalline cellulose and the carboxymethyl starch sodium through a screen to obtain the microcrystalline cellulose and the carboxymethyl starch sodium which meet the requirement of the particle size;
step S30, weighing the ranitidine hydrochloride, microcrystalline cellulose, carboxymethyl starch sodium and magnesium stearate with a first mass which meet the requirement of the particle size according to the prescription amount to obtain raw and auxiliary materials;
step S40, adding the raw and auxiliary materials into a wet granulator, mixing, adding purified water, and granulating to obtain a soft material;
step S50, granulating the soft material by using a second screen, and drying by using a fluidized bed to obtain first dry particles;
step S60, vibrating the first dry particles, and finishing the particles through a third screen to obtain second dry particles;
step S70, weighing a second mass of magnesium stearate, adding the second mass of magnesium stearate and the second dry granules, and uniformly mixing in a three-dimensional mixer to obtain target granules;
and step S80, filling the target particles to obtain the ranitidine hydrochloride capsule.
Further, in step S10, the mesh number of the first screen is 60 to 100, and may be, for example, 60, 61, 62, 63, 64, 65, 70, 80, 90, 100, or the like, and preferably 60.
Further, in step S30, the first mass is 0.3 to 3%, for example, 0.3%, 0.4%, 0.5%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, etc., preferably 1.5%, based on 100% of the total mass of the ranitidine hydrochloride capsule.
Further, in step S40, the mixing time is 5 to 10min, for example, 5min, 5.5min, 6min, 6.5min, 7min, 8min, 9min, 10min, etc., preferably 5min, and when the mixing time is too short, the mixing is not uniform.
Further, in step S50, the mesh number of the second screen is 16 to 20, and may be, for example, 16, 17, 18, 20, etc., and is preferably 16.
In the drying process using the fluidized bed, the mass content of water in the granules is controlled to be less than 0.5%, for example, 0.5%, 0.49%, 0.48%, 0.47%, 0.45%, 0.4%, 0.3%, 0.2%, 0.1%, etc., and the water content is measured by a rapid moisture meter at 105 ℃.
The fan frequency is 10-30Hz, such as 10Hz, 11Hz, 12Hz, 13Hz, 14Hz, 15Hz, 16Hz, 17Hz, 18Hz, 19Hz, 20Hz, 30Hz, etc.; when the fan frequency is too big, the material blows equipment and trembles the bag and can lose, when extension frequency is too little, does not reach the boiling state.
The material temperature is 30-40 deg.C, such as 30 deg.C, 31 deg.C, 32 deg.C, 33 deg.C, 34 deg.C, 35 deg.C, 36 deg.C, 37 deg.C, 38 deg.C, 39 deg.C, 40 deg.C, etc., when the material temperature is too low, the drying speed is slow, and when the material temperature is too high, the stability of the medicine is affected.
The temperature of the intake air is 50-70 deg.C, such as 50 deg.C, 51 deg.C, 52 deg.C, 53 deg.C, 54 deg.C, 55 deg.C, 60 deg.C, 65 deg.C, 70 deg.C, etc.
Further, in step S60, the mesh number of the third screen is 30.
Further, in step S70, the second mass is 0.3 to 3%, for example, 0.2%, 0.3%, 0.4%, 0.5%, 0.7%, 0.8%, 0.9%, 1%, 2%, etc., preferably 1%, based on 100% of the total mass of the ranitidine hydrochloride capsule.
The mixing time is 10-30min, for example, 10min, 11min, 12min, 13min, 14min, 15min, 20min, 25min, 30min, etc., when the mixing time is too short, the mixing may be non-uniform, and when the mixing time is too long, the disintegration and dissolution of the drug may be affected.
Aiming at the problems of instability, poor material fluidity and easy adhesion of the product, the invention develops a new formula, adopts a mode of adding magnesium stearate into the capsule, overcomes the defects of poor material fluidity and easy adhesion, strictly controls the moisture of the granules by drying in a fluidized bed, ensures the good stability of the capsule, and is suitable for large-scale production of ranitidine hydrochloride capsules.
The invention is described in further detail with reference to a part of the test results, which are described in detail below with reference to specific examples.
Example 1
Based on the preparation of 150mg of each capsule, the ranitidine hydrochloride capsule comprises the following components in parts by weight:
| name (R) | Weight ratio (%) | Function of |
| Ranitidine hydrochloride | 96.1％ | Active ingredient |
| Microcrystalline cellulose | 0.7％ | Filler |
| Sodium starch glycolate | 0.7％ | Disintegrating agent |
| Magnesium stearate | 2.5％ | Lubricant agent |
The preparation process comprises the following steps:
s1, screening ranitidine hydrochloride through a 60-mesh sieve to obtain ranitidine hydrochloride meeting the requirement of the particle size;
s2, respectively screening the microcrystalline cellulose and the carboxymethyl starch sodium through a screen to obtain the microcrystalline cellulose and the carboxymethyl starch sodium which meet the requirement of the particle size;
s3, weighing the ranitidine hydrochloride, the microcrystalline cellulose, the carboxymethyl starch sodium and 1.5% of magnesium stearate which meet the particle size requirement according to the prescription amount to obtain raw and auxiliary materials;
s4, adding the raw and auxiliary materials into a wet granulator, mixing for 5 minutes, adding purified water, and granulating to obtain a soft material;
s5, granulating the soft material by using a 16-mesh sieve, and drying by using a fluidized bed, wherein the frequency of a fan is 10-30Hz, the temperature of the material is 30-40 ℃, the air inlet temperature is 50-70 ℃, and the moisture content is controlled to be less than 0.5% to obtain first dry particles;
s6, vibrating the first dry particles, and sieving the first dry particles through a 30-mesh sieve to obtain second dry particles;
s7, weighing magnesium stearate with the amount of 1% of the prescription amount, adding the magnesium stearate with the amount of 1% and mixing the magnesium stearate with the second dry granules in a three-dimensional mixer for 10min to obtain target granules;
s8, filling the target particles to obtain the ranitidine hydrochloride capsule.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml of water as a dissolution medium, measuring the dissolution rate by a dissolution rate and release rate measuring method (second method of 0931 general rule) by a paddle method of 50 revolutions (adding a settling basket); the dissolution profile measurement data are shown in table one.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml of acetic acid solution with pH of 4.5 as dissolution medium, performing paddle method for 50 revolutions (adding a settling basket), and determining dissolution rate by dissolution rate and release rate determination method (second method of 0931 general rule); the dissolution profile measurement data are shown in table two.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml hydrochloric acid solution with pH of 1.2 as dissolution medium, performing paddle method for 50 revolutions (adding a settling basket), and determining dissolution rate by a dissolution rate and release rate determination method (second method of 0931 general rule); the dissolution profile measurement data are shown in table three.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml of phosphate buffer solution with pH of 6.8 as dissolution medium, performing paddle method for 50 revolutions (adding a settling basket), and determining dissolution rate by a dissolution rate and release rate determination method (second method of general rule 0931); the dissolution profile measurement data are shown in table four.
Example 2
Based on the preparation of 150mg of each capsule, the ranitidine hydrochloride capsule comprises the following components in parts by weight:
| name (R) | Weight ratio (%) | Function of |
| Ranitidine hydrochloride | 95％ | Active ingredient |
| Microcrystalline cellulose | 1％ | Filler |
| Sodium starch glycolate | 1％ | Disintegrating agent |
| Magnesium stearate | 3％ | Lubricant agent |
The preparation process comprises the following steps:
s1, screening ranitidine hydrochloride through a 60-mesh sieve to obtain ranitidine hydrochloride meeting the requirement of the particle size;
s2, respectively screening the microcrystalline cellulose and the carboxymethyl starch sodium through a screen to obtain the microcrystalline cellulose and the carboxymethyl starch sodium which meet the requirement of the particle size;
s3, weighing the ranitidine hydrochloride, the microcrystalline cellulose, the carboxymethyl starch sodium and 1.8% of magnesium stearate which meet the particle size requirement according to the prescription amount to obtain raw and auxiliary materials;
s4, adding the raw and auxiliary materials into a wet granulator, mixing for 7 minutes, adding purified water, and granulating to obtain a soft material;
s5, granulating the soft material by using a 20-mesh sieve, and drying by using a fluidized bed, wherein the frequency of a fan is 10-30Hz, the temperature of the material is 30-40 ℃, the air inlet temperature is 50-70 ℃, and the moisture content is controlled to be less than 0.5% to obtain first dry particles;
s6, vibrating the first dry particles, and sieving the first dry particles through a 30-mesh sieve to obtain second dry particles;
s7, weighing magnesium stearate with the prescription amount of 1.2%, adding the magnesium stearate with the prescription amount of 1.2% and mixing the magnesium stearate with the second dry granules in a three-dimensional mixer for 20min to obtain target granules;
s8, filling the target particles to obtain the ranitidine hydrochloride capsule.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml of water as a dissolution medium, measuring the dissolution rate by a dissolution rate and release rate measuring method (second method of 0931 general rule) by a paddle method of 50 revolutions (adding a settling basket); the dissolution profile measurement data are shown in table one.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml of acetic acid solution with pH of 4.5 as dissolution medium, performing paddle method for 50 revolutions (adding a settling basket), and determining dissolution rate by dissolution rate and release rate determination method (second method of 0931 general rule); the dissolution profile measurement data are shown in table two.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml hydrochloric acid solution with pH of 1.2 as dissolution medium, performing paddle method for 50 revolutions (adding a settling basket), and determining dissolution rate by a dissolution rate and release rate determination method (second method of 0931 general rule); the dissolution profile measurement data are shown in table three.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml of phosphate buffer solution with pH of 6.8 as dissolution medium, performing paddle method for 50 revolutions (adding a settling basket), and determining dissolution rate by a dissolution rate and release rate determination method (second method of general rule 0931); the dissolution profile measurement data are shown in table four.
Example 3
Based on the preparation of 150mg of each capsule, the ranitidine hydrochloride capsule comprises the following components in parts by weight:
| name (R) | Weight ratio (%) | Function of |
| Ranitidine hydrochloride | 91％ | Active ingredient |
| Microcrystalline cellulose | 3％ | Filler |
| Sodium starch glycolate | 1％ | Disintegrating agent |
| Magnesium stearate | 5％ | Lubricant agent |
The preparation process comprises the following steps:
s1, screening ranitidine hydrochloride through a 60-mesh sieve to obtain ranitidine hydrochloride meeting the requirement of the particle size;
s2, respectively screening the microcrystalline cellulose and the carboxymethyl starch sodium through a screen to obtain the microcrystalline cellulose and the carboxymethyl starch sodium which meet the requirement of the particle size;
s3, weighing the ranitidine hydrochloride, microcrystalline cellulose, sodium carboxymethyl starch and 3% magnesium stearate which meet the particle size requirement according to the prescription amount to obtain raw and auxiliary materials;
s4, adding the raw and auxiliary materials into a wet granulator, mixing for 9 minutes, adding purified water, and granulating to obtain a soft material;
s5, granulating the soft material by using a 16-mesh sieve, and drying by using a fluidized bed, wherein the frequency of a fan is 10-30Hz, the temperature of the material is 30-40 ℃, the air inlet temperature is 50-70 ℃, and the moisture content is controlled to be less than 0.5% to obtain first dry particles;
s6, vibrating the first dry particles, and sieving the first dry particles through a 30-mesh sieve to obtain second dry particles;
s7, weighing magnesium stearate with the prescription amount of 2%, adding the magnesium stearate with the prescription amount of 2% and the second dry granules, and mixing for 30min in a three-dimensional mixer to obtain target granules;
s8, filling the target particles to obtain the ranitidine hydrochloride capsule.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml of water as a dissolution medium, measuring the dissolution rate by a dissolution rate and release rate measuring method (second method of 0931 general rule) by a paddle method of 50 revolutions (adding a settling basket); the dissolution profile measurement data are shown in table one.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml of acetic acid solution with pH of 4.5 as dissolution medium, performing paddle method for 50 revolutions (adding a settling basket), and determining dissolution rate by dissolution rate and release rate determination method (second method of 0931 general rule); the dissolution profile measurement data are shown in table two.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml hydrochloric acid solution with pH of 1.2 as dissolution medium, performing paddle method for 50 revolutions (adding a settling basket), and determining dissolution rate by a dissolution rate and release rate determination method (second method of 0931 general rule); the dissolution profile measurement data are shown in table three.
The dissolution test of the ranitidine hydrochloride capsule is carried out, and the dissolution test conditions are as follows: taking 900ml of phosphate buffer solution with pH of 6.8 as dissolution medium, performing paddle method for 50 revolutions (adding a settling basket), and determining dissolution rate by a dissolution rate and release rate determination method (second method of general rule 0931); the dissolution profile measurement data are shown in table four.
TABLE data for dissolution curves in water of examples 1 to 3 and reference formulations
| Sampling time (min) | 5 | 10 | 15 | Similarity of characters |
| Reference formulation dissolution (%) | 18.15 | 56.93 | 86.18 | / |
| Example 1 | 30.50 | 68.94 | 88.86 | Similarity of |
| Example 2 | 26.76 | 61.22 | 89.21 | Similarity of |
| Example 3 | 25.23 | 63.12 | 87.90 | Similarity of |
。
TABLE 2 data for dissolution Curve measurements in acetate buffer medium at pH 4.5 for examples 1-3 and reference formulation
| Sampling time (min) | 10 | 15 | 20 | Similarity of characters |
| Reference formulation dissolution (%) | 50.42 | 73.98 | 88.91 | / |
| Example 1 | 48.73 | 70.17 | 80.65 | Similarity of |
| Example 2 | 49.43 | 70.66 | 81.61 | Similarity of |
| Example 3 | 47.30 | 68.51 | 80.22 | Similarity of |
。
TABLE TRI EXAMPLES 1-3 measurement data of dissolution curves of reference preparations in hydrochloric acid medium having pH of 1.2
| Sampling time (min) | 5 | 10 | 15 | 30 | 45 | Similarity of characters |
| Reference formulation dissolution (%) | 18.68 | 41.36 | 55.00 | 76.75 | 89.72 | / |
| Example 1 | 22.23 | 48.13 | 63.60 | 78.9 | 91.07 | Similarity of |
| Example 2 | 23.03 | 50.09 | 63.08 | 79.6 | 89.41 | Similarity of |
| Example 3 | 19.87 | 48.07 | 63.68 | 80.1 | 93.53 | Similarity of |
。
TABLE IV data for the determination of the dissolution curves of examples 1 to 3 and the reference preparation in phosphate buffer medium with pH 6.8
| Sampling time (min) | 5 | 10 | 15 | Similarity of characters |
| Reference formulation dissolution (%) | 18.18 | 58.61 | 87.99 | / |
| Example 1 | 24.33 | 66.70 | 90.98 | Similarity of |
| Example 2 | 22.58 | 61.51 | 87.32 | Similarity of |
| Example 3 | 25.64 | 68.12 | 89.99 | Similarity of |
。
Reference formulation
Ranitidine hydrochloride capsules;
the manufacturer: DR REDDY' S Laboratories Limited in the orange book, USA.
The dissolution test is carried out on the ranitidine hydrochloride capsule. Dissolution test conditions were as follows: taking 900ml dissolution medium, rotating 50 times by paddle method (adding a settling basket), dissolution is measured by dissolution and release determination method (second method of general rule 0931).
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (10)
1. The ranitidine hydrochloride capsule is characterized by comprising the following components in percentage by mass based on 100% of the total mass of the ranitidine hydrochloride capsule:
2. the ranitidine hydrochloride capsule according to claim 1, which comprises the following components in percentage by mass, based on 100% of the total mass of the ranitidine hydrochloride capsule:
or, the ranitidine hydrochloride capsule comprises the following components in percentage by mass:
or, the ranitidine hydrochloride capsule comprises the following components in percentage by mass:
3. a method of preparing the ranitidine hydrochloride capsule of any of claims 1 or 2, characterized by comprising the steps of:
firstly, ranitidine hydrochloride passes through a first screen to obtain ranitidine hydrochloride meeting the requirement of the particle size;
respectively sieving the microcrystalline cellulose and the carboxymethyl starch sodium by using a sieve to obtain the microcrystalline cellulose and the carboxymethyl starch sodium which meet the requirement of the particle size;
weighing the ranitidine hydrochloride, the microcrystalline cellulose, the sodium carboxymethyl starch and the magnesium stearate with the first mass which meet the requirement of the particle size according to the prescription amount to obtain raw and auxiliary materials;
adding the raw and auxiliary materials into a wet granulator, mixing, adding purified water, and granulating to obtain a soft material;
granulating the soft material by using a second screen, and drying by using a fluidized bed to obtain first dry particles;
vibrating the first dry particles, and then finishing the particles through a third screen to obtain second dry particles;
weighing a second mass of magnesium stearate, adding the second mass of magnesium stearate and the second dry granules, and uniformly mixing in a three-dimensional mixer to obtain target granules;
and filling the target particles to obtain the ranitidine hydrochloride capsule.
4. The method of claim 3, wherein the first mass is 0.3-3% based on 100% of the total mass of the ranitidine hydrochloride capsule;
and/or the second mass is 0.2-2%.
5. The method of claim 3, wherein the first mesh has a mesh size of 60 to 100;
and/or the mesh number of the second screen is 16-20;
and/or the mesh number of the third screen is 30.
6. The method for preparing ranitidine hydrochloride capsules according to claim 3, wherein the mixing time in the step of adding the raw and auxiliary materials into a wet granulator for mixing, adding purified water for granulation to obtain soft materials is 5-10 min.
7. The method of claim 3, wherein the drying with a fluidized bed is performed while controlling the moisture content of the granules to less than 0.5% by mass.
8. The method of claim 3, wherein the fan frequency is 10-30Hz during the drying process with the fluidized bed.
9. The method for preparing ranitidine hydrochloride capsules according to claim 3, wherein the material temperature is 30-40 ℃ during the drying process by the fluidized bed;
and/or the temperature of the inlet air is 50-70 ℃.
10. The method for preparing ranitidine hydrochloride capsules according to claim 3, wherein the step of weighing a second mass of magnesium stearate, adding the second mass of magnesium stearate and the second dry granules, and uniformly mixing in a three-dimensional mixer to obtain the target granules, the mixing time is 10-30 min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010114924.XA CN111202718A (en) | 2020-02-25 | 2020-02-25 | Ranitidine hydrochloride capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202010114924.XA CN111202718A (en) | 2020-02-25 | 2020-02-25 | Ranitidine hydrochloride capsule and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1299090B1 (en) * | 2000-07-11 | 2006-03-08 | Flamel Technologies | Oral pharmaceutical composition with controlled release and prolonged absorption |
| CN108670959A (en) * | 2018-06-30 | 2018-10-19 | 郑州明泽医药科技有限公司 | A kind of ranitidine hydrochloride capsules and preparation method thereof |
| CN109010303A (en) * | 2017-06-09 | 2018-12-18 | 苏州科伦药物研究有限公司 | A kind of industrial production process of ranitidine hydrochloride capsules |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1299090B1 (en) * | 2000-07-11 | 2006-03-08 | Flamel Technologies | Oral pharmaceutical composition with controlled release and prolonged absorption |
| CN109010303A (en) * | 2017-06-09 | 2018-12-18 | 苏州科伦药物研究有限公司 | A kind of industrial production process of ranitidine hydrochloride capsules |
| CN108670959A (en) * | 2018-06-30 | 2018-10-19 | 郑州明泽医药科技有限公司 | A kind of ranitidine hydrochloride capsules and preparation method thereof |
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