CN117357490A - Pirenpananel tablet and preparation method thereof - Google Patents
Pirenpananel tablet and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 45
- 239000002245 particle Substances 0.000 claims abstract description 62
- 238000000034 method Methods 0.000 claims abstract description 30
- 102220043159 rs587780996 Human genes 0.000 claims abstract description 12
- RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229960004633 pirenzepine Drugs 0.000 claims abstract description 11
- 230000008569 process Effects 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims description 43
- 229940079593 drug Drugs 0.000 claims description 37
- 238000002156 mixing Methods 0.000 claims description 34
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 24
- 239000011248 coating agent Substances 0.000 claims description 21
- 238000000576 coating method Methods 0.000 claims description 21
- 239000002994 raw material Substances 0.000 claims description 20
- 238000001035 drying Methods 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 15
- 239000000853 adhesive Substances 0.000 claims description 12
- 230000001070 adhesive effect Effects 0.000 claims description 12
- 235000019359 magnesium stearate Nutrition 0.000 claims description 12
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 10
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 10
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 10
- 229940069328 povidone Drugs 0.000 claims description 10
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 9
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 8
- 239000008101 lactose Substances 0.000 claims description 8
- 229960001375 lactose Drugs 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 238000010298 pulverizing process Methods 0.000 claims description 5
- 239000008213 purified water Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 4
- 238000007873 sieving Methods 0.000 claims description 4
- 239000000377 silicon dioxide Substances 0.000 claims description 4
- 235000012239 silicon dioxide Nutrition 0.000 claims description 4
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 229960001021 lactose monohydrate Drugs 0.000 claims description 3
- 239000007779 soft material Substances 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 239000012856 weighed raw material Substances 0.000 claims description 3
- 239000008119 colloidal silica Substances 0.000 claims description 2
- 238000007906 compression Methods 0.000 claims description 2
- 230000006835 compression Effects 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 25
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 238000011160 research Methods 0.000 description 9
- 238000005550 wet granulation Methods 0.000 description 8
- 239000000843 powder Substances 0.000 description 7
- 238000007907 direct compression Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000001037 epileptic effect Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
-
- 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
-
- 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
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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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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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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Abstract
The invention belongs to the field of medical biology, and relates to a pirenzepine tablet and a preparation method thereof. According to the invention, after different crushers are crushed, the particle size D90 is selected to be 5-30 mu m, D50=2-10 mu m is adopted to prepare the sample, so that the dissolution rate and the basic similarity of the dissolution curve and the reference are greatly improved. The preparation process flow can save energy and reduce emission in the commercial production process, reduce the production cost, has the advantages of process operability and process controllability, and stable product quality, and is basically similar to the reference dissolution trend.
Description
Technical Field
The invention belongs to the field of medical biology, and relates to a pirenzepine tablet and a preparation method thereof.
Background
Pirenzenenide tablet is an antiepileptic drug and is mainly used for treating epileptic diseases of adults and children. Can help relieve cerebral nerve dysfunction caused by epileptic diseases, and also can help relieve limb convulsion and oral leukorrhagia, and can be used for treating patients after muscle spasm and muscle convulsion.
After research, the existing pirenzenenide tablet has the following defects:
the related data are searched, the original preparation process is traditional wet granulation, the preparation process is complicated, the raw material medicine is a insoluble medicine, and the influence of the grain size on the dissolution trend of the preparation is large.
Therefore, the invention increases the research of the dry preparation process of the variety on the basis of wet granulation, simplifies the preparation steps on the basis of ensuring the consistency with the dissolution trend of the original grinding, can save energy and reduce emission in the commercial production process, reduces the production cost, improves the process operability and process controllability, and has stable product quality. In addition, the invention carries out research control on the particle size of the bulk drug, and can provide reference for subsequent researches.
Disclosure of Invention
The invention aims to provide a preparation method of a pirenzepine tablet.
1) Crushing the raw materials: respectively crushing the pirenzenenape by adopting a hammer crusher, an air flow crusher and an ultra-micro crusher to obtain bulk drugs with the D90 of 5-30 mu m and the D50=2-10 mu m particle size;
2) And (3) adhesive preparation: adding povidone according to the prescription amount into purified water, stirring and adding until the povidone is completely dissolved for later use;
3) Granulating: placing the weighed raw material medicines, lactose monohydrate and low-substituted hydroxypropyl cellulose into a wet granulator for mixing, adding a proper amount of adhesive for granulating after uniformly mixing;
4) Drying and dry granulating: drying the soft material in a drying oven at a temperature below 60 ℃ until the moisture is less than or equal to 2-4%, and then drying and granulating by a granulating machine;
5) Total mixing: weighing the low-substituted hydroxypropyl cellulose and magnesium stearate as the external auxiliary materials according to the prescription proportion, placing the mixture in a mixer, firstly mixing the mixture with the low-substituted hydroxypropyl cellulose, and then adding the magnesium stearate for mixing;
6) Tabletting: compressing the finally mixed granules into tablets using a high-speed tablet compression device;
7) Coating: the tablet is coated by using a high-efficiency coating machine.
Preferably, the particle diameter D90 of the bulk drug is not more than 13 μm, and D50 is less than 3 μm.
The invention also provides another preparation method for preparing the pirenzeneb tablet by a powder direct compression method.
1) Pulverizing the raw materials, sieving with 80 mesh sieve, and using raw materials with particle diameter D90 of 5-30 μm and d50=2-10 μm;
2) Mixing the raw materials with microcrystalline cellulose, and granulating;
3) Mixing the mixture of the raw material medicine and microcrystalline cellulose with lactose;
4) Mixing with silicon dioxide and magnesium stearate;
5) Tabletting: tabletting by using a high-speed rotary tablet press;
6) Coating: the tablet is coated by using a high-efficiency coating machine.
Preferably, the particle diameter D90 of the bulk drug is not more than 13 μm, and D50 is less than 3 μm.
The pirenzeneb is crushed by different crushers and different preparation methods, and the crushed pirenzeneb is selected to have the particle size D90 of 5-30 mu m and D50=2-10 mu m for preparing samples. The prepared samples are prepared by adopting different preparation process modes, namely wet granulation and direct powder tabletting, so that the dissolution rate and the basic similarity of dissolution curves and references are greatly improved, and the preparation process flow can save energy and reduce emission, reduce the production cost, and has the advantages of stable product quality and basically similar dissolution trend with references in the commercial production process.
The technical improvement of the invention mainly consists in controlling the particle sizes D90 and D50, and the effect is optimal when the D90 is not higher than 10 mu m-13 mu m.
Besides the technical improvement, the research of a dry preparation process is added on the basis of an original grinding wet granulation preparation process, and compared with the wet preparation process, the dry preparation process has the advantages of simpler steps, optimal production amplification effect, easier realization of workshop amplification, stable quality indexes, energy saving and emission reduction in production, reduced production cost, process operability and process controllability and stable product quality.
Drawings
FIG. 1, pirenpananel test particle size trend results
FIG. 1-1 Markov (wet) test results after pulverizing crude drugs with a micronizer
FIG. 1-2 Markov (Wet) test results of an uncrushed drug substance
FIG. 2 influence of Pirenpananel bulk drug with different particle sizes on dissolution trend of preparation
FIG. 3 comparison of dissolution tendency of Pirenpananel tablets prepared by different granulation methods
Detailed Description
The invention is further illustrated by the following examples.
The products and methods of making the same are further illustrated in the following examples, but the invention is not limited to the following examples. The methods are conventional methods unless otherwise specified. The starting materials are available from published commercial sources unless otherwise specified.
Test example,
1. Preparation process method
Particle size investigation and research of the pirenzenenape bulk drug are carried out, particle size comparison and research are carried out on the crushed bulk drug by different crushing equipment, particle size investigation and research are carried out on API (application program interface) by adopting a hammer crusher, an air flow crusher and an ultrafine crusher, and particle size detection is carried out on the bulk drug by adopting a Markov laser particle size analyzer, so that the bulk drug with the particle size of D90 of 5-30 mu m and D50=2-10 mu m is obtained. The method adopts a wet granulation mode to prepare samples by using crude drugs with different particle sizes respectively, and the influence of the particle sizes of the crude drugs on the dissolution trend of the preparation is examined.
1. Prescription of prescription
| Adhesive preparation | Weighing amount/g |
| 25% povidone | Proper amount of |
| Purified water | Proper amount of |
2. Preparation process
1) Crushing the raw materials: the particle size comparison research of the API is carried out by respectively adopting a hammer mill, an air flow mill and an ultrafine mill, and the particle size of the crude drug is detected by a Markov particle size meter (wet method) to obtain the crude drug with the D90 of 5-30 mu m and the D50=2-10 mu m. And (3) respectively preparing samples by using crude drugs with different particle sizes, and examining the influence of the particle sizes of the crude drugs on the dissolution trend of the preparation.
2) And (3) adhesive preparation: adding povidone according to the prescription amount into purified water, stirring and adding until the povidone is completely dissolved for later use;
3) Granulating: the weighed raw materials, lactose monohydrate and low-substituted hydroxypropyl cellulose are placed into a wet granulator to be mixed, and a proper amount of adhesive is added for granulating after the mixture is uniformly mixed.
4) Drying and dry granulating: drying the soft material in a drying oven at a temperature below 60 ℃ until the moisture is less than or equal to 2-4%, and then drying and granulating by a granulator.
5) Total mixing: weighing the low-substituted hydroxypropyl cellulose and magnesium stearate as the external auxiliary materials according to the prescription proportion, placing the mixture in a mixer, mixing the mixture with the low-substituted hydroxypropyl cellulose, and then adding the magnesium stearate for mixing.
6) Tabletting: the final mixed granules were compressed into tablets using a high speed tablet press.
7) Coating: the tablet is coated by using a high-efficiency coating machine.
2. Particle size trend results of pirenzenenaphthalene detection
The results of particle size trend detection after crushing by different crushers are shown in figure 1.
3. Results of preparation of samples from pirenzenenaphthalene of different particle sizes
Example 1 process steps: and (3) crushing the pirenzenenaphthalene by adopting a jet mill, detecting the particle size by using a Markov (wet method), obtaining a bulk drug with the particle size D90 of 6.89 mu m and D50=2.40 mu m, uniformly mixing the bulk drug with the sieved auxiliary materials, adding an adhesive to prepare wet particles, drying at the temperature of 60 ℃, uniformly mixing the particles, tabletting and coating.
Example 2 process steps: and (3) crushing the pirenzenenaphthalene by adopting an ultrafine crusher, detecting the particle size by using a Markov (wet method), obtaining a bulk drug with the particle size D90 of 5.10 mu m and D50=2.31 mu m, uniformly mixing the bulk drug with the sieved auxiliary materials, adding an adhesive to prepare wet particles, drying at 60 ℃, uniformly mixing the particles, tabletting and coating.
Example 3 process steps: and (3) crushing the pirenzenenaphthalene by a mechanical crusher, detecting the particle size by using a Markov (wet method), obtaining a bulk drug with the particle size D90 of 13 mu m and D50=2.99 mu m, uniformly mixing the bulk drug with the sieved auxiliary materials, adding an adhesive to prepare wet particles, drying at 60 ℃, uniformly mixing the particles, tabletting and coating.
Example 4 process steps: and (3) crushing the pirenzenenaphthalene by a hammer crusher, detecting the particle size by using a Markov (wet method), obtaining a bulk drug with the particle size D90 of 21 mu m and D50=5.99 mu m, uniformly mixing the bulk drug with the sieved auxiliary materials, adding an adhesive to prepare wet particles, drying at 60 ℃, uniformly mixing the particles, tabletting and coating.
Example 5 process steps: the particle size of the non-crushed pirenzenenaphthalene is detected by a Markov (wet method), the particle size D90 is 30 mu m, D50=9.29 mu m, the non-crushed pirenzenenaphthalene and the sieved auxiliary materials are uniformly mixed, the mixture is added with a binder to prepare wet particles, and the wet particles are dried at 60 ℃ and then are subjected to tabletting and coating after the total uniform mixing.
Chart 2 influence of particle size of different crude drugs on dissolution tendency of the preparation
As can be seen from FIG. 2, when the particle diameter D90 of the crude drug is 5-13 μm and D50 is less than 3 μm, the dissolution trend of the preparation is not obviously different, but when the particle diameter D90 of the crude drug is increased to 21-30 μm and D50 is more than 5.9 μm, the dissolution trend of the preparation in a pH3.0 medium is obviously slowed down, and the dissolution end point is reduced by nearly 50%.
The particle size of the pirenzenenaphthalene bulk drug directly influences the dissolution trend of the preparation, and when the particle size D90 is more than 13 mu m and the D50 is more than 5.9 mu m, the dissolution trend of the preparation is obviously slowed down.
3. Results of different process steps
The preparation method comprises the steps of respectively adopting wet granulation and direct powder tabletting to prepare the pirenzepine tablet, wherein the preparation method adopts bulk drugs with the particle size D90 of 5.10 mu m and D50=2.31 mu m, and the dissolution trend of the pirenzepine tablet under different granulation modes is examined. Specific wet granulation formulation procedures are described in the first section (example 2); specific formulations and processes for direct compression of powders are described below (example 6):
1. powder direct compression formula
| Pirenpananel tablet | Specification 4mg |
| Pirenpananel hydrate | 10.50 |
| Lactose and lactose | 121.26 |
| Microcrystalline cellulose | 60.64 |
| Crosslinked povidone | 5.00 |
| Colloidal silica | 0.60 |
| Magnesium stearate | 2.00 |
| Coating liquid | Proper amount of |
2. Powder direct tabletting process step
1) Pulverizing the raw materials, sieving with 80 mesh sieve, and using raw materials with particle diameter D90 of 5 μm and d50=2.31 μm;
2) Mixing the raw materials with microcrystalline cellulose, and granulating;
3) Mixing the mixture of the raw material medicine and microcrystalline cellulose with lactose;
4) Mixing with silicon dioxide and magnesium stearate;
5) Tabletting: tabletting by using a high-speed rotary tablet press;
6) Coating: the tablet is coated by using a high-efficiency coating machine.
Chart 3 comparison of dissolution curves of samples prepared by different granulation methods
Fig. 3 can be seen: when the particle diameter D90 of the pirenzepine drug substance is 5.10 μm and d50=2.31 μm, the pirenzepine tablet is prepared by respectively adopting wet granulation and powder direct compression, and the dissolution trend of the preparation is basically consistent.
For the pirenzepine tablet, the particle size of the bulk drug has larger influence on the dissolution trend, when the particle size D90 of the bulk drug is less than or equal to 13 mu m and D50 is less than 3 mu m, the dissolution rate of the preparation in a pH3.0 medium can reach more than 85% in 60min, and different granulating modes can reach the same dissolution trend. However, when the particle diameter D90 of the crude drug is larger than 21 μm and the D50 is larger than 5.9 μm, the dissolution end point of the preparation is obviously reduced.
The foregoing is merely a preferred embodiment of the present invention, and it should be noted that the embodiment of the present invention is not limited by the examples. Several changes, modifications, substitutions, combinations, and simplifications can be made without departing from the principles of the present invention, and the changes, modifications, substitutions, combinations, and simplifications should be considered as equivalent substitutions.
Claims (6)
1. A preparation method of a pirenzepine tablet comprises the following steps:
1) Crushing the raw materials: respectively crushing the pirenzenenape by adopting a hammer crusher, an air flow crusher and an ultra-micro crusher to obtain bulk drugs with the D90 of 5-30 mu m and the D50=2-10 mu m particle size;
2) And (3) adhesive preparation: adding povidone according to the prescription amount into purified water, stirring and adding until the povidone is completely dissolved for later use;
3) Granulating: placing the weighed raw material medicines, lactose monohydrate and low-substituted hydroxypropyl cellulose into a wet granulator for mixing, adding a proper amount of adhesive for granulating after uniformly mixing;
4) Drying and dry granulating: drying the soft material in a drying oven at a temperature below 60 ℃ until the moisture is less than or equal to 2-4%, and then drying and granulating by a granulating machine;
5) Total mixing: weighing the low-substituted hydroxypropyl cellulose and magnesium stearate as the external auxiliary materials according to the prescription proportion, placing the mixture in a mixer, firstly mixing the mixture with the low-substituted hydroxypropyl cellulose, and then adding the magnesium stearate for mixing;
6) Tabletting: compressing the finally mixed granules into tablets using a high-speed tablet compression device;
7) Coating: the tablet is coated by using a high-efficiency coating machine.
2. A preparation method of a pirenzepine tablet comprises the following steps:
1) Pulverizing the raw materials, sieving with 80 mesh sieve, and using raw materials with particle diameter D90 of 5-30 μm and d50=2-10 μm;
2) Mixing the raw materials with microcrystalline cellulose, and granulating;
3) Mixing the mixture of the raw material medicine and microcrystalline cellulose with lactose;
4) Mixing with silicon dioxide and magnesium stearate;
5) Tabletting: tabletting by using a high-speed rotary tablet press;
6) Coating: the tablet is coated by using a high-efficiency coating machine.
3. The preparation method according to claim 1 or 2, wherein the bulk drug has a particle size D90 of not more than 13 μm and a D50 of < 3 μm.
4. The method of claim 1, wherein the prescription composition is as follows:
5. A preparation method of a pirenzepine tablet comprises the following steps:
prescription of prescription
The process comprises the following steps:
1) Pulverizing the raw materials, sieving with 80 mesh sieve, and using raw materials with particle diameter D90 of 5-30 μm and d50=2-10 μm;
2) Mixing the raw materials with microcrystalline cellulose, and granulating;
3) Mixing the mixture of the raw material medicine and microcrystalline cellulose with lactose;
4) Mixing with silicon dioxide and magnesium stearate;
5) Tabletting: tabletting by using a high-speed rotary tablet press;
6) Coating: the tablet is coated by using a high-efficiency coating machine.
6. The preparation method according to claim 1, wherein the bulk drug has a particle size D90 < 13 μm and a D50 < 3 μm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311458297.1A CN117357490A (en) | 2023-11-03 | 2023-11-03 | Pirenpananel tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311458297.1A CN117357490A (en) | 2023-11-03 | 2023-11-03 | Pirenpananel tablet and preparation method thereof |
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| Publication Number | Publication Date |
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| CN117357490A true CN117357490A (en) | 2024-01-09 |
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| CN202311458297.1A Pending CN117357490A (en) | 2023-11-03 | 2023-11-03 | Pirenpananel tablet and preparation method thereof |
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| Country | Link |
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| CN (1) | CN117357490A (en) |
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