CN107753455B - A tablet containing imidafenacin and its preparation method - Google Patents
A tablet containing imidafenacin and its preparation method Download PDFInfo
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
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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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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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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- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
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Abstract
The invention discloses a tablet containing imidafenacin and a preparation method thereof, wherein the tablet or a tablet core thereof comprises an active component imidafenacin, a filling agent, a bonding agent and a lubricating agent, during the preparation process, the active component is firstly dissolved in an ethanol solvent or an ethanol-water mixed solvent, then the bonding agent and water are added to prepare a bonding agent solution, and then the bonding agent solution, the filling agent and the lubricating agent are granulated and tabletted. The invention can ensure that the finished product is dissolved out quickly, and in the application, the raw materials and the adhesive are dissolved in the ethanol solution step by step and then added into other mixed powder in a solution state, so that the content uniformity can be greatly improved; the reduced pressure drying process is adopted, and the air is isolated, so that the oxidative degradation impurities of the material can be well reduced. The technical scheme of the invention has the advantages of rapid dissolution, small oxidized impurities, good content uniformity and the like, and the preparation process is simple and is suitable for large-scale production.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an imidafenacin tablet and a preparation method thereof.
Background
Overactive bladder (OAB) is a syndrome characterized by symptoms of urgency, often accompanied by frequency, urgency, and nocturia, or by urge incontinence, which severely reduces the quality of life of the patient. About 5 million to 1 million people all over the world suffer from overactive bladder, more than diabetes and peptic ulcerIt is common. Imidafenacin has a diphenylbutanamide structure, is a novel high-efficiency anticholinergic agent, selectively acts on M3 and M1 receptors, blocks the contraction action of choline on detrusor muscle, and has fewer central and peripheral adverse reactions. Imidafenacin tablet (trade name)
) Marketed in japan in 6 months of 2007 with a specification of 0.1 mg.
Because the product has extremely small specification, the content uniformity of the product needs to be focused in the production process; it was found that imidafenacin is prone to oxidative degradation impurities at high temperatures, and thus the formation of such oxidative impurities can be reduced during sample preparation by avoiding drying processes (direct compression of the powder), reducing drying time (fluidized bed granulation or partial granulation) or by air isolation (vacuum drying).
Chinese patent CN102579393A discloses a solid composition for improving the content uniformity and dissolution of imidafenacin, wherein the raw and auxiliary materials are micronized to improve the dissolution and bioavailability of the drug; CN 102861010A spray-drying imidafenacin and alpha-cyclodextrin aqueous solution to obtain granules, and then carrying out subsequent treatment to improve the in vitro dissolution rate; in the research process, the solubility of the imidafenacin in water is extremely low, but the dissolution belongs to a quick dissolution type under the condition of proper prescription composition and proportion due to extremely small specification, and the in-vitro dissolution is improved without adding a working procedure.
Chinese patent CN103479594B provides a imidafenacin film tablet and a preparation method thereof, which adopts a fluidized bed granulation process, tabletting and coating to obtain a sample with qualified dissolution and content uniformity.
Chinese patent CN104415034A discloses a imidafenacin pharmaceutical composition with good content uniformity, rapid dissolution and excellent stability and a preparation method thereof, wherein the imidafenacin is firstly dissolved by using an inert non-volatile solvent, then a porous auxiliary material is selected to absorb the drug to obtain powder, and finally the powder is mixed with a disintegrant and an excipient to be tableted. The process is complex to operate, and has limited choice of auxiliary materials, especially nonvolatile solvents, and the dosage must be very low, and the operation is limited.
Chinese patent CN106580899A discloses a method for preparing imidafenacin tablets, which comprises dissolving imidafenacin and cosolvent in absolute ethanol, spraying into adjuvant, adding lubricant, mixing, and tabletting.
Disclosure of Invention
The invention aims to provide an imidafenacin tablet which has good content uniformity, quick dissolution and stable related substances on the basis of the prior art.
The invention also aims to provide a preparation method of the imidafenacin tablet.
The technical scheme of the invention is as follows:
the imidafenacin tablet is a tablet or a tablet core formed by raw material medicines and excipients, wherein the raw material medicines are imidafenacin, and the excipients comprise: fillers, binders and lubricants.
Furthermore, the imidafenacin tablet or the tablet core thereof comprises an active component imidafenacin, a filling agent, a bonding agent and a lubricating agent, during the preparation process, the active component is firstly dissolved in an ethanol solvent or an ethanol-water mixed solvent, then the bonding agent and water are added to prepare a bonding agent solution, and then the bonding agent solution, the filling agent and the lubricating agent are granulated and tabletted.
In a preferable scheme, in the preparation process of the imidafenacin tablet, the active ingredients are firstly added into an ethanol-water mixed solvent, after stirring and dissolving, the adhesive is added to be uniformly dispersed and dissolved, and finally, water is added to be uniformly stirred to prepare the adhesive solution. Experiments show that the adding sequence of the components in the preparation process of the imidafenacin tablet influences the uniformity, the dissolution speed and the content of related substances of the tablet. The preparation process includes dissolving the active component imidafenacin in alcohol-water solvent, adding adhesive and water to prepare adhesive solution containing active component, and adding other supplementary material to pelletize. Experiments show that compared with other wet granulation methods, the method provided by the invention can improve the dissolution rate of the preparation, improve the content of active substances in the preparation, effectively improve the content uniformity of each preparation, reduce the total impurity content and the maximum single impurity content in the product, and improve the dissolution rate of active ingredients.
In a preferred embodiment, the imidafenacin tablet is prepared by slowly adding the filler to the binder solution to form a soft mass, followed by granulation, drying the resulting wet granules, mixing with the lubricant, tabletting, and coating.
In the process of granulating the tablets, the drying mode can be a reduced-pressure drying process, a forced air drying process or a boiling drying process, but the invention finds that the content of impurities in the product can be reduced to the maximum extent by adopting the reduced-pressure drying process, so that the total impurity content and the maximum single impurity content in the product are both minimized, and the storage and the use of the tablets are more facilitated. Preferably, in the reduced pressure drying process, the vacuum degree is-0.05 to-0.5 MPa, the drying temperature is 45 to 65 ℃, the drying time is 3 to 5 hours, and the water content is less than or equal to 5 percent.
In a more preferable scheme, the ethanol-water mixed solvent is 90-99% of ethanol-water mixed solvent, the filler is selected from microcrystalline cellulose and pregelatinized starch, and the lubricant is selected from magnesium stearate; the binder is selected from povidone.
In one scheme, the imidafenacin tablet comprises a tablet core and a coating, wherein the tablet core comprises the following components in parts by mass: 0.06-0.1 part of imidafenacin, 40-65 parts of pregelatinized starch, 45-65 parts of microcrystalline cellulose, 1-5 parts of povidone and 0.2-1 part of magnesium stearate.
In another scheme, the tablet core comprises the following components in percentage by mass: 0.06-0.1% of imidafenacin, 40-65% of pregelatinized starch, 45-65% of microcrystalline cellulose, 301-5% of povidone K and 0.2-1% of magnesium stearate.
In a preferred embodiment, the tablet core comprises the following components in parts by mass: 0.06-0.08 part of imidafenacin, 40-50 parts of pregelatinized starch, 45-55 parts of microcrystalline cellulose, 1-3 parts of povidone and 0.2-0.5 part of magnesium stearate.
In another preferred scheme, the mass percentages of the components of the tablet core are as follows: the mass percentage of the imidafenacin is 0.06-0.08%, the pregelatinized starch is 40-50%, the microcrystalline cellulose is 45-55%, the povidone K is 301-3%, and the magnesium stearate is 0.2-0.5%.
In the invention, povidone is adopted as the adhesive, and experiments show that the tablet can be maintained at a higher dissolution speed, a lower total impurity content and a maximum single impurity content when the dosage of the adhesive is kept in a reasonable range, and the effect is difficult to achieve by using an excessively high or excessively low dosage of the adhesive. The preferable amount of the adhesive is 1 to 5 parts or 1 to 5%, and more preferably 1 to 3 parts or 1 to 3%.
In a preferred embodiment, the tablet core comprises the following components in parts by mass: 1.0 part of imidafenacin, 650 parts of pregelatinized starch, 750 parts of microcrystalline cellulose, 42 parts of povidone, 4 parts of magnesium stearate and 420 parts of coating agent.
In a preferred embodiment, the tablet core comprises the following components in parts by mass: 1.0 part of imidafenacin, 700 parts of pregelatinized starch, 700 parts of microcrystalline cellulose, 28 parts of povidone, 6 parts of magnesium stearate and 420 parts of coating agent.
In another preferred embodiment, the tablet core comprises the following components in parts by mass: 1.0 part of imidafenacin, 650 parts of pregelatinized starch, 750 parts of microcrystalline cellulose, 21 parts of povidone, 4 parts of magnesium stearate and 420 parts of coating agent.
The coating of the tablet of the present invention may be made of the existing gastric soluble film coating material.
The invention provides a preparation method of imidafenacin tablets, which comprises the following steps:
(1) pretreatment: sieving active ingredients and adjuvants;
(2) preparation of adhesive solution: dissolving the active component in ethanol solvent or ethanol-water mixed solvent, and then adding adhesive and water to prepare adhesive solution;
(3) granulating, tabletting and coating: slowly adding filler into binder solution to obtain soft mass, granulating, drying, mixing with lubricant, tabletting, and coating.
In the preparation process of the imidafenacin tablet, the imidafenacin is taken and added into a proper amount of 95 percent ethanol, after stirring and dissolving, the adhesive povidone K30 is added, and finally a proper amount of purified water is added to obtain 35-50 percent (preferably 40-50 percent) v/v ethanol water solution containing the original drug; uniformly mixing pregelatinized starch and microcrystalline cellulose, slowly adding the above medicinal binder, granulating with 20 mesh sieve, and grading to 20-80 (preferably 20-60) mesh sieve.
In the tablet preparation method, the preferred granulation process is as follows: taking imidafenacin, adding a proper amount of 95% ethanol, stirring for dissolving, then adding a binding agent povidone K30, and finally adding a proper amount of purified water to obtain a 48% v/v ethanol water solution containing the original medicine; uniformly mixing pregelatinized starch and microcrystalline cellulose, slowly adding the above medicine-containing adhesive, granulating with 20 mesh, and grading with 20-80 (preferably 20-60) mesh.
In the preparation of the tablet, the drying mode can be a reduced pressure drying process, a forced air drying process or a boiling drying process, but the invention finds that the content of impurities in the product can be reduced to the maximum extent by adopting the reduced pressure drying process, so that the total impurity content and the maximum single impurity content in the product are both minimized, and the storage and the use of the tablet are more facilitated. Preferably, in the reduced pressure drying process, the vacuum degree is-0.05 to-0.5 MPa, the drying temperature is 45 to 65 ℃, the drying time is 3 to 5 hours, and the water content is less than or equal to 5 percent.
According to the preparation method of the tablet, the box opening times in the drying process is less than or equal to three times.
By adopting the technical scheme of the invention, the advantages are as follows:
according to the scheme provided by the invention, the raw material medicine does not need to be subjected to micro powder or other treatment, the finished product can be ensured to be dissolved out quickly, and the finished product can be completely dissolved out within about 5 min. In the preparation method, the raw material medicine and the adhesive are dissolved in the ethanol solution step by step and then added into other mixed powder in a solution state, so that the content uniformity can be greatly improved; further adopting a process of isolating air and reducing pressure for drying; through the mutual synergistic effect of all the characteristics, the final product can better reduce the oxidative degradation impurities of the active ingredients, ensure that related substances are superior to the original ground product, improve the content of effective substances in the preparation and effectively ensure the content uniformity of all the preparations; the auxiliary material variety provided by the invention is completely consistent with the original ground product, the process is simple, and the operability is strong.
Preparation examples
The invention is further illustrated by the following examples, without restricting the content of the invention to these.
Example 1
Tablet formulation (10000 formulation unit weight):
the preparation process comprises the following steps:
1. pretreatment of
1.1, preparing materials: weighing pregelatinized starch and microcrystalline cellulose according to the formula ratio, and respectively sieving with a 80-mesh sieve for later use.
1.2 preparation of adhesive solution: adding the formula amount of imidafenacin into 480g of 95% ethanol, stirring for dissolving, slowly adding 42g of povidone K30 for uniformly dispersing, stirring for dissolving, adding 600g of purified water, and stirring for later use.
2. Granulating, drying, and grading
2.1 mixing the microcrystalline cellulose and the pregelatinized starch evenly, slowly adding the midazolam povidone K30 ethanol water solution to prepare soft mass, and granulating with 20 meshes.
2.2 placing the wet granules in a decompression drying oven, drying at 50 ℃ until the moisture of the granules is not higher than 5%, and finishing the granules with 20 meshes.
3. Total mixing
And mixing the granules with magnesium stearate in the formula amount for 10 minutes, and detecting an intermediate.
4. Tabletting
Determining the weight of the intermediate, selecting a phi 7.0mm shallow concave punch for tabletting, and obtaining the hardness: 30N-70N; difference in tablet weight: 7.5 percent.
5. Coating film
5.1 preparation of coating liquid: weighing 420g of gastric-soluble film coating powder, slowly adding into 2kg of purified water, and continuously stirring for 45 minutes after the coating powder is completely added and uniformly dispersed;
5.2 putting the plain tablets into a high-efficiency coating machine, and increasing the weight of the coating to 2-5%.
Example 2
Tablet formulation (10000 formulation unit weight):
the preparation process comprises the following steps:
1. pretreatment of
1.1, preparing materials: weighing pregelatinized starch and microcrystalline cellulose according to the formula ratio, and respectively sieving with a 80-mesh sieve for later use.
1.2 preparation of adhesive solution: adding the formula amount of imidafenacin into 480g of 95% ethanol, stirring for dissolving, slowly adding 28g of povidone K30 for uniformly dispersing, stirring for dissolving, adding 600g of purified water, and stirring for later use.
2. Granulating, drying, and grading
2.1 mixing the microcrystalline cellulose and the pregelatinized starch evenly, slowly adding the midazolam povidone K30 ethanol water solution to prepare soft mass, and granulating with 20 meshes.
2.2 placing the wet granules in a decompression drying oven, drying at 50 ℃ until the moisture of the granules is not higher than 5%, and finishing the granules with 20 meshes.
3. Total mixing
And mixing the granules with magnesium stearate in the formula amount for 10 minutes, and detecting an intermediate.
4. Tabletting
Determining the weight of the intermediate, selecting a phi 7.0mm shallow concave punch for tabletting, and obtaining the hardness: 30N-70N; difference in tablet weight: 7.5 percent.
5. Coating film
5.1 preparation of coating liquid: weighing 420g of gastric-soluble film coating powder, slowly adding into 2kg of purified water, and continuously stirring for 45 minutes after the coating powder is completely added and uniformly dispersed;
5.2 putting the plain tablets into a high-efficiency coating machine, and increasing the weight of the coating to 2-5%.
Example 3
Tablet formulation (10000 formulation unit weight):
the preparation process comprises the following steps:
1. pretreatment of
1.1, preparing materials: weighing pregelatinized starch and microcrystalline cellulose according to the formula ratio, and respectively sieving with a 80-mesh sieve for later use.
1.2 preparation of adhesive solution: adding the formula amount of imidafenacin into 48g of 95% ethanol, stirring for dissolving, slowly adding 21g of povidone K30 for uniformly dispersing, stirring for dissolving, adding 60g of purified water, and stirring for later use.
2. Granulating, drying, and grading
2.1 taking part of microcrystalline cellulose, slowly adding the imidafenacin povidone K30 ethanol solution to prepare soft mass, and granulating with 20 meshes.
2.2 placing the wet granules in a decompression drying oven, drying at 50 ℃ until the moisture of the granules is not higher than 5%, and finishing the granules with 60 meshes.
3. Total mixing
Mixing the granules with the rest microcrystalline cellulose, pregelatinized starch and magnesium stearate in formula amount for 10min, and detecting intermediate.
4. Tabletting
Determining the weight of the intermediate, selecting a phi 7.0mm shallow concave punch for tabletting, and obtaining the hardness: 30N-70N; difference in tablet weight: 7.5 percent.
5. Coating film
5.1 preparation of coating liquid: weighing 420g of gastric-soluble film coating powder, slowly adding into 2kg of purified water, and continuously stirring for 45 minutes after the coating powder is completely added and uniformly dispersed;
5.2 putting the plain tablets into a high-efficiency coating machine, and increasing the weight of the coating to 2-5%.
Comparative example 1
Tablet formulation (10000 formulation unit weight):
the preparation process comprises the following steps:
1. pretreatment of
1.1, preparing materials: the imidafenacin, the pregelatinized starch and the microcrystalline cellulose are weighed according to the formula and respectively sieved by a sieve of 80 meshes for later use.
1.2 preparation of adhesive solution: 480g of 95% ethanol is slowly added with 36g of povidone K30 for uniform dispersion, stirred and dissolved, and added with 600g of purified water for uniform stirring for later use.
2. Granulating, drying, and grading
2.1 taking the formula amount of imidafenacin, respectively mixing the imidafenacin with the pregelatinized starch and the microcrystalline cellulose step by a gradual mixing method, slowly adding the adhesive solution to prepare a soft material, and granulating by 20 meshes.
2.2 placing the wet granules in a decompression drying oven, drying at 50 ℃ until the moisture of the granules is not higher than 5%, and finishing the granules with 20 meshes.
3. Total mixing
And mixing the granules with the magnesium stearate with the formula amount for 10 minutes, and detecting an intermediate.
4. Tabletting
Determining the weight of the intermediate, selecting a phi 7.0mm shallow concave punch for tabletting, and obtaining the hardness: 30N-70N; difference in tablet weight: 7.5 percent.
5. Coating film
5.1 preparation of coating liquid: weighing 420g of gastric-soluble film coating powder, slowly adding into 2kg of purified water, and continuously stirring for 45 minutes after the coating powder is completely added and uniformly dispersed;
5.2 putting the plain tablets into a high-efficiency coating machine, and increasing the weight of the coating to 2-5%.
Comparative example 2
Tablet formulation (10000 formulation unit weight):
the preparation process comprises the following steps:
the remaining steps were referred to example 1 using a forced air drying process (oven drying) at 50 ℃ until the moisture of the pellets was not higher than 5%.
Comparative example 3
Tablet formulation (10000 formulation unit weight):
the preparation process comprises the following steps:
adopting a boiling drying process, wherein the air inlet temperature is as follows: 60 ℃, material temperature: 40 ℃, fan frequency: 25 Hz. Drying is stopped when the moisture of the granules is less than or equal to 5.0 percent. The rest of the procedure was referred to example 1.
Comparative example 4(CN103479594B comparative example 1)
Tablet formulation (on a per 10000 tablet basis):
the preparation process comprises the following steps:
1) taking the raw material of the pyridazone, crushing, and sieving with a 200-mesh sieve for later use;
2) slowly adding the raw material of the pyridazone into prepared 60% ethanol water solution, stirring and dissolving to be used as an adhesive for later use;
3) placing microcrystalline cellulose and pregelatinized starch in a wet mixing granulator, stirring for 8 minutes, slowly and uniformly adding binder dissolved with the imadazoline into the materials, rinsing the binder storage container with a proper amount of 60% ethanol water solution, adding into the materials together to prepare soft materials, sieving with a 24-mesh sieve, and granulating;
4) drying the wet granules in a hot air circulation oven at 50 +/-5 ℃, controlling the water content to be 1.0-3.0%, granulating, calculating the recovery rate, adding magnesium stearate, and uniformly mixing;
5) intermediate product physical examination: calculating the theoretical weight of the tablet according to the main theoretical content, calculating the tablet weight control range by +/-5% of the theoretical weight of the tablet, and selecting a 7mm round shallow punched tablet;
6) coating is carried out by taking Opadry as film coating agent and preparing coating solution from 80% ethanol water solution, wherein the weight of the coating is increased to 3% -5%.
7) And taking the film coated tablet, and packaging with polyvinyl chloride solid medicinal hard tablet, aluminum foil for medicine packaging and aluminum-plastic composite bag.
Comparative example 5(CN106361716A comparative example 1)
Tablet formulation (on a per 1000 tablet basis):
the preparation process comprises the following steps:
uniformly mixing the pregelatinized starch, microcrystalline cellulose (PH102) and povidone K30 at room temperature for 10 min; dispersing and dissolving the imidafenacin with the formula amount in a proper amount of absolute ethyl alcohol for later use; spraying the anhydrous ethanol containing the main drug into the auxiliary materials, adding magnesium stearate with the formula amount, and mixing uniformly for 10 min. Tabletting and coating. Measuring the content of the intermediate; wherein the hardness of the pressed sheet is 8kg, and the mould is 7mm shallow concave.
Example 4 verification of Effect (see the fourth part of the 2015 edition Chinese pharmacopoeia for examination items)
1. The content uniformity of the samples of the examples and the comparative examples (general rule 0941) was determined, and the specific results are shown in Table 1
Table 1 example content uniformity test results
| Sample (I) | Content (%) | Content uniformity (A +2.2S) |
| Example 1 | 97.1 | 6.3 |
| Example 2 | 98.5 | 5.7 |
| Example 3 | 96.7 | 6.1 |
| Comparative example 1 | 99.6 | 11.0 |
| Comparative example 2 | 97.5 | 5.8 |
| Comparative example 3 | 96.9 | 6.0 |
| Comparative example 4 | / | 10.62(A+1.8S) |
| Comparative example 5 | / | 13.87(A+1.8S) |
2. The samples of the examples and comparative examples were examined for the substances, and the results are shown in Table 2
HPLC method:
a chromatographic column: octadecylsilane chemically bonded silica (5 μm, 4.6. mu. mm. about.250 mm, trade name: Inertsil ODS-3)
Solution A: phosphoric acid solution of sodium octane sulfonate (1.08 g sodium octane sulfonate, 0.1% diluted phosphoric acid solution (1 → 1000) is dissolved and diluted to 1000ml, and pH is adjusted to 2.8 with triethylamine)
And B, liquid B: acetonitrile for liquid chromatography
Mobile phase: the gradient is controlled by changing the mixing ratio of the solution A and the solution B
A detector: UV (ultraviolet) light
Measuring wavelength: 220nm
TABLE 2 results of detection of substances of interest in examples
3. The disintegration time of the samples of examples and comparative examples (general rule 0921) was examined, and the specific results are shown in Table 3
TABLE 3 detection results of disintegration time limit of samples
4. The dissolution rates of the samples (general rule 0931) of the examples and comparative examples were measured, and the specific results are shown in Table 4
Table 4 dissolution test results of samples in examples
Claims (1)
1. A tablet of imidafenacin, characterized in that 10000 formulation unit of the tablet is prepared from the following components by mass: 1.0g of imidafenacin, 700g of pregelatinized starch, PH 101700 g of microcrystalline cellulose, povidone K3028 g, 6g of magnesium stearate and 420g of coating agent; the preparation process of the tablet comprises the following steps:
(1) pretreatment of
Preparing materials: weighing pregelatinized starch and microcrystalline cellulose according to the formula ratio, and respectively sieving with a 80-mesh sieve for later use;
preparation of adhesive solution: adding the formula amount of imidafenacin into 480g of 95% ethanol, stirring for dissolving, slowly adding 28g of povidone K30 for uniformly dispersing, stirring for dissolving, adding 600g of purified water, and stirring for later use;
(2) granulating, drying, and grading
Mixing microcrystalline cellulose and pregelatinized starch, slowly adding midazolam povidone K30 ethanol water solution to make soft mass, and granulating with 20 mesh sieve;
placing the wet granules in a reduced pressure drying oven, drying at 50 deg.C until the moisture of the granules is not higher than 5%, and grading with 20 mesh sieve;
(3) total mixing of
Mixing the granules with magnesium stearate in a formula amount for 10 minutes, and detecting an intermediate;
(4) and tabletting
Determining the weight of the intermediate, selecting a phi 7.0mm shallow concave punch for tabletting, and obtaining the hardness: 30N-70N; difference in tablet weight: 7.5 percent;
(5) coating the mixture
Preparing a coating solution: weighing 420g of gastric-soluble film coating powder, slowly adding into 2kg of purified water, and continuously stirring for 45 minutes after the coating powder is completely added and uniformly dispersed;
the plain tablets are put into a high-efficiency coating machine, and the coating weight is increased to 2 to 5 percent.
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| CN110068623B (en) * | 2019-04-08 | 2022-04-12 | 南京海纳医药科技股份有限公司 | Method for detecting related substances in imidafenacin |
| CN110772490A (en) * | 2019-10-31 | 2020-02-11 | 宁波高新区美诺华医药创新研究院有限公司 | Preparation method of apixaban tablets |
| CN113109461B (en) * | 2021-03-02 | 2023-05-09 | 南京海纳医药科技股份有限公司 | Method for detecting related substances in imidafenacin tablets |
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| 咪达那新片处方工艺及质量标准研究;张进;《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》;20170315(第03期);B016-1270，第15-16页第2.2.2.2、2.2.2节，第17页第2.2.2.5节，第21页第3.4节，第17-18页第2.3.1节，第28页第3.5.3.5节 * |
| 杨如意等.溶剂分散法制备咪达那新片.《中国药剂学杂志》.2017,第15卷(第4期),第85-91页，第87页第2.6节，第90页第2.12节，第89页第2.10节. * |
| 溶剂分散法制备咪达那新片;杨如意等;《中国药剂学杂志》;20170731;第15卷(第4期);第85-91页，第87页第2.6节，第90页第2.12节，第89页第2.10节 * |
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