CN111450074A - Mycophenolate mofetil capsule and preparation method thereof - Google Patents
Mycophenolate mofetil capsule and preparation method thereof Download PDFInfo
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- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 title claims abstract description 52
- 229960004866 mycophenolate mofetil Drugs 0.000 title claims abstract description 52
- 239000002775 capsule Substances 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 44
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract description 23
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 23
- 229920000881 Modified starch Polymers 0.000 claims abstract description 22
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 22
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 19
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 19
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229940069328 povidone Drugs 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 12
- 230000008569 process Effects 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims description 34
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 21
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 21
- 239000008187 granular material Substances 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 238000007873 sieving Methods 0.000 claims description 10
- 229920003082 Povidone K 90 Polymers 0.000 claims description 8
- 238000011049 filling Methods 0.000 claims description 8
- 239000008213 purified water Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 238000010008 shearing Methods 0.000 claims description 6
- 239000007779 soft material Substances 0.000 claims description 6
- 238000005550 wet granulation Methods 0.000 claims description 4
- 229940057948 magnesium stearate Drugs 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 abstract description 16
- 239000000126 substance Substances 0.000 abstract description 7
- 239000002245 particle Substances 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 abstract 2
- 239000002994 raw material Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 3
- -1 2-morpholinoethyl Chemical group 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 229940107810 cellcept Drugs 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 229960000951 mycophenolic acid Drugs 0.000 description 2
- 238000007613 slurry method Methods 0.000 description 2
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000212 effect on lymphocytes Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 239000013037 reversible inhibitor Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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Abstract
The invention discloses a mycophenolate mofetil capsule and a preparation method thereof, wherein the mycophenolate mofetil capsule contains mycophenolate mofetil, pregelatinized starch, cross-linked sodium carboxymethyl cellulose, povidone and magnesium stearate, and the weight ratio of the mycophenolate mofetil to the pregelatinized starch to the cross-linked sodium carboxymethyl cellulose to the povidone to the magnesium stearate is 1: (0.08-0.15): (0.05-0.08): (0.01-0.02): (0.02-0.03). The mycophenolate mofetil capsule provided by the invention is fast in dissolution, the dissolution rate is consistent with that of a reference preparation, related substances are stable and controllable in the process of accelerating the preparation, the provided preparation method is simple in process, and particles obtained by fluidized bed drying are uniform in particle size and good in liquidity, so that the mycophenolate mofetil capsule is suitable for the requirement of mass production.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a mycophenolate mofetil capsule and a preparation method thereof.
Background
Mycophenolate mofetil, chemical name: 2-morpholinoethyl (E) -6- (1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl) -4-methyl-4-ethenium salt having the formula C23H31NO7Molecular weight 433.50, chemical formula:
mycophenolate mofetil was developed by Roche (Roche) company of switzerland under the trade name Cellcept, and its capsules, tablets, injection and dry suspension were approved by FDA for marketing at 5/3/1995, 6/19/1997, 8/12/1998 and 10/1/1998, respectively, and the original research capsule was marketed at home in 2013. Mycophenolate mofetil is an immunosuppressant, has high oral bioavailability, can be rapidly absorbed and metabolized into active ingredient mycophenolic acid (MPA) after being taken orally, and the MPA is a high-efficiency, selective, noncompetitive and reversible inhibitor of inosine mononucleotide dehydrogenase (IMPDH), can inhibit the classical synthetic pathway of guanine nucleotide, enables the depletion of the guanine nucleotide and further blocks the synthesis of DNA. MPA has a highly selective effect on lymphocytes and can inhibit their proliferation. Mycophenolate mofetil is used for preventing rejection after organ transplantation and treating acute and refractory rejection after transplantation, such as kidney transplantation and liver transplantation, thereby improving the survival rate of transplanted patients. The capsule is one of common dosage forms, has the advantages of fast absorption, high bioavailability, improved drug stability, covering the unpleasant odor of the drug and the like compared with a tablet or a dispersing agent, and only a few reports about the preparation of the mycophenolate mofetil capsule exist at present.
Disclosure of Invention
The invention aims to provide a mycophenolate mofetil capsule which is controllable in quality, good in stability and consistent in dissolution behavior with a reference preparation.
In order to realize the purpose of the invention, the technical scheme provided by the invention is as follows:
the mycophenolate mofetil capsule mainly comprises the following components in parts by weight:
preferably, the mycophenolate mofetil capsule mainly comprises the following components in parts by weight:
the polyvidone is polyvidone K-90.
The preparation method of the mycophenolate mofetil capsule comprises the following steps:
uniformly mixing mycophenolate mofetil with pregelatinized starch, croscarmellose sodium and povidone, performing wet granulation to obtain a soft material, drying the granules in a fluidized bed until the moisture content is less than 2%, granulating the dried granules, adding magnesium stearate, totally mixing, and filling into capsules.
Preferably, the preparation method of the mycophenolate mofetil capsule comprises the following steps:
a. sieving mycophenolate mofetil, pregelatinized starch, croscarmellose sodium, povidone and magnesium stearate for later use;
b. mixing croscarmellose sodium and povidone for 2-5 minutes, adding pregelatinized starch, mixing for 2-5 minutes, adding one fifth of the prescribed amount of mycophenolate mofetil, mixing for 3-8 minutes, and finally adding the rest of the prescribed amount of mycophenolate mofetil, mixing for 8-12 minutes to obtain a mixture;
c. wet granulating the mixture, adding purified water while stirring, and shearing to obtain granules;
d. drying with fluidized bed until the water content is less than 2%;
e. and (3) finishing the dried granules, adding magnesium stearate, mixing for 2-5 minutes, and filling into capsules to obtain the capsule.
In the step a, the sieving is to pass through a 60-20-mesh sieve, preferably a 40-mesh sieve.
In the step b, the croscarmellose sodium and the povidone are mixed for 3 minutes, then the pregelatinized starch is added and mixed for 3 minutes, then one fifth of the prescribed amount of mycophenolate mofetil is added and mixed for 5 minutes, and finally the rest of the prescribed amount of mycophenolate mofetil is added and mixed for 10 minutes to obtain a mixture.
In the step c, during wet granulation, the stirring speed is 200-400 rpm, preferably 200rpm, and the weight of the purified water is 40-50%, preferably 45% of the total weight of the mycophenolate mofetil, the pregelatinized starch, the croscarmellose sodium, the povidone and the magnesium stearate.
In the step d, the air inlet temperature during fluidized bed drying is 50-60 ℃, preferably 60 ℃, and the air inlet frequency is 30-70%, preferably 50%.
In step e, magnesium stearate is added and mixed for 3 minutes.
Further preferably, the preparation method of the mycophenolate mofetil capsule comprises the following steps:
a. weighing raw and auxiliary materials according to a proportion, and sieving the raw and auxiliary materials by a 40-mesh sieve for later use;
b. mixing croscarmellose sodium and povidone K-90 for 3 minutes, adding pregelatinized starch, mixing for 3 minutes, adding one fifth of the raw materials, and mixing for 5 minutes; and finally, adding the rest raw materials in the prescription amount and mixing for 10 minutes to obtain a mixture.
c. Adding the mixture into a wet granulator, stirring, adding purified water, shearing to prepare soft materials, and granulating the obtained granules by a conical granulator;
d. drying with fluidized bed until the water content is less than 2%;
e. and (4) granulating the dried granules by using a conical granulator, adding magnesium stearate, mixing for 3 minutes, and filling capsules to obtain the final product.
The invention has the positive effects that: the mycophenolate mofetil capsule provided by the invention is fast in dissolution, the dissolution rate is consistent with that of a reference preparation, related substances are stable and controllable in the process of accelerating the preparation, the provided preparation method is simple in process, and particles obtained by fluidized bed drying are uniform in particle size and good in liquidity, so that the mycophenolate mofetil capsule is suitable for the requirement of mass production.
Drawings
Fig. 1 is a dissolution profile of mycophenolate mofetil capsules of example 1.
Detailed Description
The present invention will be described in detail below with reference to examples and drawings, but the following examples should not be construed as limiting the scope of the present invention. The reference preparation used in the invention is: mycophenolate mofetil capsule, trade name cept (Cellcept), specification: 250mg, manufacturer: shanghai Roche pharmaceuticals, Inc.
Example 1:
the formula is as follows: 750g of mycophenolate mofetil, 89.28g of pregelatinized starch, 35.7g of croscarmellose sodium, K-9017.85 g of povidone and 13.5g of magnesium stearate
The preparation process comprises the following steps:
a. taking 750g of mycophenolate mofetil, 89.28g of pregelatinized starch, 35.7g of croscarmellose sodium, 13.5g of povidone K-9017.85 and 13.5g of magnesium stearate according to the preparation dosage of 3000 granules, and respectively sieving the granules by a 40-mesh sieve for later use;
b. mixing croscarmellose sodium and povidone K-90 for 3 minutes, adding pregelatinized starch, mixing for 3 minutes, adding one fifth of the raw materials, and mixing for 5 minutes; then adding the raw materials of the rest prescription amount and mixing for 10 min.
c. Adding the mixture into a wet granulator, stirring (200rpm), adding purified water accounting for 45% of the total weight of the raw and auxiliary materials, shearing to prepare soft materials, and granulating the obtained granules by using a conical granulator;
d. fluidized bed drying (60 deg.C, air intake frequency 50%) to water content less than 2%;
e. and (4) granulating the dried granules by a conical granulator, adding magnesium stearate with the prescription amount, mixing for 3 minutes, and filling capsules to obtain the final product.
Example 2
The formula is as follows: 750g of mycophenolate mofetil, 60g of pregelatinized starch, 45g of croscarmellose sodium, K-907.5g of povidone and 18.75g of magnesium stearate
The preparation process comprises the following steps:
a. taking mycophenolate mofetil, pregelatinized starch, croscarmellose sodium, povidone K-90 and magnesium stearate according to the dosage of 3000 granules, and respectively sieving with a 40-mesh sieve for later use;
b. mixing croscarmellose sodium and povidone K-90 for 2 minutes, adding pregelatinized starch, mixing for 2 minutes, adding one fifth of the raw materials, and mixing for 3 minutes; then adding the raw materials of the rest prescription amount and mixing for 8 min.
c. Adding the mixture into a wet granulator, stirring at 300rpm, adding purified water accounting for 40% of the total weight of the raw and auxiliary materials, shearing to prepare soft materials, and granulating the obtained granules by using a conical granulator;
d. fluidized bed drying (50 deg.C, air inlet frequency 40%) to water content less than 2%;
e. and (4) granulating the dried granules by a conical granulator, adding magnesium stearate with the prescription amount, mixing for 2 minutes, and filling capsules to obtain the final product.
Example 3
The formula is as follows: 750g of mycophenolate mofetil, 112.5g of pregelatinized starch, 60g of croscarmellose sodium, K-9011.25 g of povidone and 22.5g of magnesium stearate
The preparation process comprises the following steps:
a. taking mycophenolate mofetil, pregelatinized starch, croscarmellose sodium, povidone K-90 and magnesium stearate according to the dosage of 3000 granules, and respectively sieving with a 40-mesh sieve for later use;
b. mixing the croscarmellose sodium and the povidone K-90 for 2-5 minutes, then adding the pregelatinized starch, mixing for 5 minutes, adding one fifth of the raw materials, and mixing for 8 minutes; then adding the raw materials of the rest prescription amount and mixing for 12 min.
c. Adding the mixture into a wet granulator, stirring at 400rpm, adding purified water accounting for 50% of the total weight of the raw and auxiliary materials, shearing to prepare soft materials, and granulating the obtained granules by using a conical granulator;
d. fluidized bed drying (55 deg.C, air intake frequency 45%) to water content less than 2%;
e. and (4) granulating the dried granules by a conical granulator, adding magnesium stearate with the prescription amount, mixing for 5 minutes, and filling capsules to obtain the final product.
Verification of the examples:
test example 1: comparison of dissolution curves of mycophenolate mofetil capsules of the invention with a reference formulation
According to the second dissolution determination method, 0.1 mol/L hydrochloric acid solution 900m L is used as a dissolution medium, the temperature is kept at 37 ℃, the rotating speed is 40 revolutions per minute, the solution 5m L is respectively taken in 5, 10, 15, 20, 30, 45 and 60 minutes, the solution is filtered, the absorbance is determined at the wavelength of 304nm according to an ultraviolet spectrophotometry, a proper amount of mycophenolate mofetil reference substances are precisely weighed, 0.1 mol/L hydrochloric acid solution is added for dissolution and quantitative dilution to prepare 0.055mg of solution in each 1m L, the absorbance is determined by the same method, the dissolution amount of each particle is calculated, and the limit is 80 percent of the marked amount and is in accordance with the specification.
The dissolution curves of the mycophenolate mofetil capsules prepared in example 1 of the present invention and the reference preparation are shown in table 1, and the dissolution curve chart is shown in fig. 1.
TABLE 1 comparison of dissolution Curve data
| Time min | 5 | 10 | 15 | 20 | 30 | 45 | 60 |
| Example 1 | 72.3 | 94.4 | 98.6 | 100.4 | 100.2 | 100.5 | 100.1 |
| Reference formulation | 68.1 | 89.8 | 96.3 | 98.6 | 98.7 | 99.3 | 99.1 |
Test example 2: accelerated test
The product of the invention example 1 and the reference preparation were taken and placed at 40 ℃ and humidity of 75% for sampling and detecting related substances after accelerated for 1 and 2 months, and the results are shown in the following table 2.
TABLE 2 results of comparison of related substances
| Sample name | Impurity F (%) | Impurity A (%) | Number of unknown impurities | Total impurities (%) |
| Example 1-0Month | 0.052 | 0.052 | 3 | 0.296 |
| Example 1-1Month | 0.074 | 0.057 | 2 | 0.252 |
| Example 1-2Month | 0.076 | 0.049 | 3 | 0.248 |
| Reference formulation-0 Month | 0.044 | 0.033 | 3 | 0.216 |
| Reference formulation-1 Month | 0.064 | 0.033 | 2 | 0.188 |
| Reference preparation-2 Month | 0.096 | 0.031 | 2 | 0.227 |
The comparison result shows that the dissolution curve of the capsule provided by the invention has no obvious difference with a reference preparation, and the quality is proved to be consistent; the accelerated related substances have no obvious change, which shows that the capsule provided by the invention has stable and controllable quality.
Comparative example 1
The experimental prescription for investigating the dosage of the disintegrant croscarmellose sodium is as follows:
the preparation process comprises the following steps: same as in example 1. The dissolution test results of the obtained capsules are shown in Table 3.
Table 3: dissolution data of the capsules obtained with different amounts of disintegrant in acetate pH4.0 (slurry method, 50rpm, 37 ℃, n ═ 4)
Note: n-4 means that 4 granules were used
Comparative example 2
The experimental prescription is examined on the dosage of the adhesive povidone K-90:
the preparation process comprises the following steps: same as in example 1. The dissolution test results of the obtained capsules are shown in Table 4.
Table 4: dissolution data of the capsules obtained with different amounts of binder in acetate at pH4.0 (slurry method, 50rpm, 37 ℃, n ═ 4)
Note: n-4 means that 4 pellets were used.
Claims (10)
1. The mycophenolate mofetil capsule is characterized by mainly comprising the following components in parts by weight:
2. the mycophenolate mofetil capsule according to claim 1, wherein the mycophenolate mofetil capsule consists essentially of the following components in parts by weight:
3. the mycophenolate mofetil capsule according to claim 1, wherein the povidone is povidone K-90.
4. A process for the preparation of mycophenolate mofetil capsules according to any one of claims 1 to 3, comprising the steps of:
uniformly mixing mycophenolate mofetil with pregelatinized starch, croscarmellose sodium and povidone, performing wet granulation to obtain a soft material, drying the granules in a fluidized bed until the moisture content is less than 2%, granulating the dried granules, adding magnesium stearate, totally mixing, and filling into capsules.
5. The method according to claim 4, characterized in that it comprises the following steps:
a. sieving mycophenolate mofetil, pregelatinized starch, croscarmellose sodium, povidone and magnesium stearate for later use;
b. mixing croscarmellose sodium and povidone for 2-5 minutes, adding pregelatinized starch, mixing for 2-5 minutes, adding one fifth of the prescribed amount of mycophenolate mofetil, mixing for 3-8 minutes, and finally adding the rest of the prescribed amount of mycophenolate mofetil, mixing for 8-12 minutes to obtain a mixture;
c. wet granulating the mixture, adding purified water while stirring, and shearing to obtain granules;
d. drying with fluidized bed until the water content is less than 2%;
e. and (3) finishing the dried granules, adding magnesium stearate, mixing for 2-5 minutes, and filling into capsules to obtain the capsule.
6. The method according to claim 5, wherein in step a, the sieving is 60-20 mesh sieving, preferably 40 mesh sieving.
7. The method of claim 5, wherein in step b, the croscarmellose sodium and the povidone are mixed for 3 minutes, then the pregelatinized starch is added and mixed for 3 minutes, then one fifth of the prescribed amount of mycophenolate mofetil is added and mixed for 5 minutes, and finally the remaining prescribed amount of mycophenolate mofetil is added and mixed for 10 minutes to obtain a mixture.
8. The process according to claim 5, wherein in step c, the stirring speed during wet granulation is 200-400 rpm, preferably 200rpm, and the weight of the purified water is 40-50%, preferably 45%, of the total weight of mycophenolate mofetil, pregelatinized starch, croscarmellose sodium, povidone, and magnesium stearate.
9. The method of claim 5, wherein in the step d, the temperature of the inlet air during the fluidized bed drying is 50-60 ℃, preferably 60 ℃, and the frequency of the inlet air is 30-70%, preferably 50%.
10. The method of claim 5, wherein in step e, magnesium stearate is added and mixed for a total of 3 minutes.
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| CN112438959A (en) * | 2020-12-11 | 2021-03-05 | 南京佰麦生物技术有限公司 | Method for preparing mycophenolate mofetil capsules by melting method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106389379A (en) * | 2016-11-29 | 2017-02-15 | 无锡福祈制药有限公司 | Mycophenolate mofetil capsule and preparation method thereof |
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- 2019-01-21 CN CN201910051239.4A patent/CN111450074A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106389379A (en) * | 2016-11-29 | 2017-02-15 | 无锡福祈制药有限公司 | Mycophenolate mofetil capsule and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112438959A (en) * | 2020-12-11 | 2021-03-05 | 南京佰麦生物技术有限公司 | Method for preparing mycophenolate mofetil capsules by melting method |
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Application publication date: 20200728 |