CN113855638B - Roflumilast pharmaceutical preparation - Google Patents

Roflumilast pharmaceutical preparation Download PDF

Info

Publication number
CN113855638B
CN113855638B CN202111264283.7A CN202111264283A CN113855638B CN 113855638 B CN113855638 B CN 113855638B CN 202111264283 A CN202111264283 A CN 202111264283A CN 113855638 B CN113855638 B CN 113855638B
Authority
CN
China
Prior art keywords
cyclodextrin
roflumilast
parts
beta
pharmaceutical preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202111264283.7A
Other languages
Chinese (zh)
Other versions
CN113855638A (en
Inventor
刘营营
杨西邈
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beijing Fuyuan Pharmaceutical Co ltd
Original Assignee
Beijing Fuyuan Pharmaceutical Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Beijing Fuyuan Pharmaceutical Co ltd filed Critical Beijing Fuyuan Pharmaceutical Co ltd
Priority to CN202111264283.7A priority Critical patent/CN113855638B/en
Publication of CN113855638A publication Critical patent/CN113855638A/en
Application granted granted Critical
Publication of CN113855638B publication Critical patent/CN113855638B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • 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
    • A61K9/2022—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
    • 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
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a roflumilast pharmaceutical preparation, which comprises Luo Shasi, cyclodextrin derivatives, polacrilin potassium, diluents and disintegrants, wherein the particle size d0.9 of Luo Shasi is not more than 30 mu m. The roflumilast pharmaceutical preparation prepared by the invention has better dissolution rate, and ensures the quality and the curative effect of the medicine.

Description

Roflumilast pharmaceutical preparation
Technical Field
The invention relates to a medicinal preparation of a hypoxia-inducible factor prolyl hydroxylase inhibitor, in particular to a roflumilast medicinal preparation and a preparation method of the preparation.
Background
Renal anemia is an anemia caused by the progression of various Chronic Kidney Diseases (CKD), often associated with a relative or absolute insufficiency of the secretion of erythropoietin by the renal interstitium and a reduced sensitivity of the patient to the disease, a shortened lifetime of the erythrocytes, a change in the microenvironment of the bone marrow hematopoietic system, iron deficiency, etc., and severe renal anemia increases the mortality of CKD patients. About 1.195 million CKD patients in our country, about 40 tens of thousands of which are subject to dialysis (or peritoneal dialysis), are rapidly increasing in two digits per year, and thus there are increasing numbers of patients who need to treat renal anemia.
Luo Shasi he (orezedown roxadat, RDXT), developed in combination with Fabry-Perot (fibrigen), aspirin (AstraZeneca) and An Si Tay (Astella), is a drug for treating renal anemia (chronic kidney disease, CKD) with small molecule hypoxia inducible factor prolyl hydroxylase inhibitors developed for the first time worldwide. The roflumilast stabilizes HIF, inhibits degradation of HIF, activates transcription of related genes, generates corresponding physiological reaction, moderately increases the concentration of erythropoietin, improves the sensitivity of Erythropoietin (EPO) receptors, coordinates erythropoiesis, reduces the level of hepcidin, increases the content and activity of transferrin receptors, promotes the absorption and utilization of iron, and has good tolerance. The medicine is a global original research medicine which is hatched in the nature of China for the first time and is obtained in China for the first time, and is used for dialysis dependent chronic renal failure anemia.
Luo Shasi his chemical name is [ (4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl) -amino ] -acetic acid. The structural formula is as follows:
Figure BDA0003324983670000011
the roflumilast has poor water solubility, and the solubility in water is only 1.71mg/L, thus being a poorly soluble drug. WO 2004108681A1 discloses Luo Shasi he compounds. WO 2014014835A2 discloses Luo Shasi other than amorphous roflumilast in several crystalline forms such as amorphous form a, hemihydrate form B, hexafluoro-propan-2-ol solvate form C and mixed DMSO/water solvate form D. The application also mentions several of his crystalline and amorphous salts of Luo Shasi, for example with alkali metals sodium and potassium, with alkaline earth metals calcium and magnesium, with the amino acids L-arginine and L-lysine, with the amines ethanolamine, diethanolamine, tromethamine and triethylamine, and with hydrochloric acid, sulfuric acid and methanesulfonic acid. WO2014197660A1 discloses the use of an effective amount of photostabilizer to increase the stability of a roflumilast pharmaceutical formulation such that the pharmaceutical formulation has a photolytic product of less than about 0.2% w/w. However, the problem of indissolvable roflumilast is not solved, so how to prepare the roflumilast into a pharmaceutical preparation, and the problem of indissolvable Luo Shasi is solved, and the problem that good dissolution is needed to be solved is solved.
Disclosure of Invention
The invention provides a roflumilast pharmaceutical preparation, which aims to solve the problems of poor water solubility and poor dissolution effect of roflumilast. The roflumilast pharmaceutical preparation prepared by the invention has better dissolution. The pharmaceutical formulation comprises in particular Luo Shasi he, cyclodextrin derivatives, polacrilin potassium, diluents and disintegrants, wherein Luo Shasi his particle size d0.9 is not more than 30 μm.
For solid preparations, the dissolution rate of the drug directly affects the absorption rate of the drug, and reducing the particle size of the active ingredient according to the Noyes-Whitney equation is one of the effective methods for improving the dissolution rate of the drug. In general, the particle size is reduced, and the surface area is increased, which contributes to the improvement of the dissolution rate. The invention aims to solve the problems of poor water solubility and low dissolution rate of the roflumilast, and reduces the particle size d0.9 of Luo Shasi of the invention to below 30 mu m. Although particle size reduction can increase dissolution, the problem of dissolution of the roflumilast pharmaceutical preparation still cannot be well solved, and further research prescriptions are needed to improve the dissolution of the roflumilast pharmaceutical preparation. Through a great deal of researches, the inventor surprisingly discovers that the particle size d0.9 of Luo Shasi is reduced to be less than 30 mu m, and the problem of dissolution of the roflumilast pharmaceutical preparation can be well solved by adding cyclodextrin derivatives and polacrilin potassium in a matching way, so that the pharmaceutical quality and the curative effect are ensured.
In some embodiments, the particle size d0.9 of roflumilast in the Luo Shasi he pharmaceutical formulation is 10-20 μm.
In the Luo Shasi pharmaceutical preparation, the cyclodextrin derivative is selected from one or more of hydroxyethyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, dihydroxypropyl-beta-cyclodextrin, methyl-beta-cyclodextrin, glucose-cyclodextrin, maltose-cyclodextrin, maltotriose-cyclodextrin and carboxymethyl-cyclodextrin; preferably, the cyclodextrin derivative is hydroxypropyl-beta-cyclodextrin.
In the Luo Shasi pharmaceutical preparation, the disintegrating agent is one or more of sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crospovidone and croscarmellose sodium.
In the Luo Shasi pharmaceutical preparation, the diluent is one or more of microcrystalline cellulose, mannitol, lactose, pregelatinized starch, sucrose, sorbitol and calcium hydrophosphate.
In the Luo Shasi pharmaceutical preparation, the mass dosages of the components of the pharmaceutical preparation are as follows: luo Shasi he 20-100 parts, cyclodextrin derivative 50-100 parts, polacrilin potassium 3-8 parts, diluent 150-250 parts and disintegrating agent 3-8 parts.
In some embodiments, the preferred roflumilast pharmaceutical formulation comprises the following components by mass: luo Shasi he 20-100 parts, 50-100 parts of hydroxypropyl-beta-cyclodextrin, 3-8 parts of polacrilin potassium, 120-200 parts of lactose, 30-50 parts of microcrystalline cellulose and 3-8 parts of croscarmellose sodium.
In some embodiments, the above pharmaceutical formulation further comprises a binder and/or lubricant.
In the Luo Shasi pharmaceutical preparation, the binder is one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and povidone.
In the Luo Shasi pharmaceutical preparation, the lubricant is one or more of superfine silica powder, talcum powder, magnesium stearate and sodium stearyl fumarate.
The invention also provides a method for preparing the roflumilast pharmaceutical preparation, which comprises the following steps:
(1) Uniformly mixing roflumilast, cyclodextrin derivatives, polacrilin potassium, a diluent and a disintegrating agent to prepare a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Tabletting the drug particles.
The step (1) further comprises a step of adding an adhesive.
The step (3) further comprises the step of uniformly mixing the drug particles with the lubricant.
Compared with the prior art, the invention has the beneficial effects that:
1. the invention reduces the particle diameter d0.9 of Luo Shasi to below 30 mu m, and can well solve the problem of poor dissolution effect of the roflumilast by adding cyclodextrin derivatives and polacrilin potassium auxiliary materials.
2. In the roflumilast pharmaceutical preparation, when the cyclodextrin derivative is further selected as hydroxypropyl-beta-cyclodextrin, the salt of the polacrilin is matched with the cyclodextrin derivative, and the particle size d0.9 of the roflumilast is controlled to be reduced to be less than 30 mu m, the well-dissolved roflumilast pharmaceutical preparation can be obtained.
3. Furthermore, in the roflumilast pharmaceutical preparation, when the cyclodextrin derivative is further selected as hydroxypropyl-beta-cyclodextrin, and the cyclodextrin derivative is matched with the polacrilin potassium, lactose, microcrystalline cellulose, croscarmellose sodium and the particle size d0.9 of the roflumilast is controlled to be reduced to be less than 30 mu m, the roflumilast pharmaceutical preparation with better dissolution can be obtained.
Detailed Description
Example 1
Composition of the composition Dosage (g)
Luo Shasi he 50
Hydroxypropyl-beta-cyclodextrin 80
Potassium polacrilin 6
Lactose and lactose 170
Microcrystalline cellulose 43
Croscarmellose sodium 7
Luo Shasi he d0.9=18 μm
The preparation method comprises the following steps:
(1) Mixing roflumilast, hydroxypropyl-beta-cyclodextrin, polacrilin potassium, lactose, microcrystalline cellulose and croscarmellose sodium uniformly to obtain a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Tabletting the drug particles.
Example 2
Composition of the composition Dosage (g)
Luo Shasi he 100
Hydroxypropyl-beta-cyclodextrin 50
Potassium polacrilin 8
Lactose and lactose 200
Microcrystalline cellulose 30
Croscarmellose sodium 8
Luo Shasi he d0.9=15 μm
The preparation method is the same as in example 1.
Example 3
Composition of the composition Dosage (g)
Luo Shasi he 20
Hydroxypropyl-beta-cyclodextrin 100
Potassium polacrilin 3
Lactose and lactose 120
Microcrystalline cellulose 50
Croscarmellose sodium 3
Luo Shasi he d 0.9=20 μm
The preparation method is the same as in example 1.
Example 4
Figure BDA0003324983670000041
Figure BDA0003324983670000051
Luo Shasi he d 0.9=25 μm
The preparation method comprises the following steps:
(1) Mixing roflumilast, hydroxyethyl-beta-cyclodextrin, polacrilin potassium, pregelatinized starch, low-substituted hydroxypropyl cellulose and crosslinked povidone uniformly to prepare a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Tabletting the drug particles.
Example 5
Composition of the composition Dosage (g)
Luo Shasi he 50
Glucose-cyclodextrin 80
Potassium polacrilin 6
Dibasic calcium phosphate 35
Mannitol (mannitol) 137
Sodium carboxymethyl starch 8
Luo Shasi he d 0.9=16 μm
The preparation method comprises the following steps:
(1) Mixing roflumilast, glucose-cyclodextrin, polacrilin potassium, calcium hydrophosphate, mannitol and sodium carboxymethyl starch uniformly to prepare a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Tabletting the drug particles.
Example 6
Composition of the composition Dosage (g)
Luo Shasi he 50
Maltose-cyclodextrin 55
Potassium polacrilin 8
Microcrystalline cellulose 50
Sorbitol 100
Crosslinked povidone 6
Hydroxypropyl cellulose 6
Luo Shasi he d 0.9=10μm
The preparation method comprises the following steps:
(1) Mixing roflumilast, maltose-cyclodextrin, polacrilin potassium, microcrystalline cellulose, sorbitol, crospovidone and hydroxypropyl cellulose uniformly to obtain a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Tabletting the drug particles.
Example 7
Composition of the composition Dosage (g)
Luo Shasi he 20
Dihydroxypropyl-beta-cyclodextrin 35
Carboxymethyl-cyclodextrins 45
Potassium polacrilin 7
Sucrose 40
Lactose and lactose 125
Crosslinked povidone 6
Hydroxypropyl methylcellulose 7
Magnesium stearate 4
Luo Shasi he d 0.9=12 μm
The preparation method comprises the following steps:
(1) Uniformly mixing roflumilast, dihydroxypropyl-beta-cyclodextrin, carboxymethyl-cyclodextrin, polacrilin potassium, sucrose, lactose, crospovidone and hydroxypropyl methylcellulose to prepare a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Mixing the medicinal granule with magnesium stearate, and tabletting.
Example 8
Composition of the composition Dosage (g)
Luo Shasi he 100
Maltotriose-cyclodextrin 65
Potassium polacrilin 7
Dibasic calcium phosphate 30
Lactose and lactose 165
Croscarmellose sodium 7
Micro powder silica gel 2
Talc powder 2
Luo Shasi he d 0.9=10μm
The preparation method comprises the following steps:
(1) Mixing roflumilast, maltotriose-cyclodextrin, polacrilin potassium, calcium hydrophosphate, lactose and crosslinked sodium carboxymethyl cellulose uniformly to prepare a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Mixing the medicinal granule with silica gel micropowder, and pulvis Talci, and tabletting.
Example 9
Figure BDA0003324983670000071
Figure BDA0003324983670000081
Luo Shasi he d 0.9=30 μm
The preparation method comprises the following steps:
(1) Mixing roflumilast, methyl-beta-cyclodextrin, polacrilin potassium, lactose, sorbitol and low-substituted hydroxypropyl cellulose uniformly to obtain a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Mixing the medicinal granule with sodium stearyl fumarate, and tabletting.
Example 10
Composition of the composition Dosage (g)
Luo Shasi he 50
Hydroxypropyl-beta-cyclodextrin 90
Potassium polacrilin 6
Microcrystalline cellulose 45
Mannitol (mannitol) 205
Croscarmellose sodium 7
Sodium carboxymethyl cellulose 4
Povidone 3
Luo Shasi he d 0.9=5 μm
The preparation method comprises the following steps:
(1) Uniformly mixing roflumilast, hydroxypropyl-beta-cyclodextrin, polacrilin potassium, microcrystalline cellulose, mannitol, croscarmellose sodium, sodium carboxymethylcellulose and povidone to prepare a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Tabletting the drug particles.
Comparative examples
Figure BDA0003324983670000082
Figure BDA0003324983670000091
The preparation method is the same as in example 1.
Dissolution investigation
Samples prepared in examples 1 to 10 and comparative formulas 1 to 5 were taken, phosphate buffer solution of pH6.5 was used as a dissolution medium, and dissolution was carried out at 75 rpm according to a dissolution rate measurement method (second method of appendix X C of 2010 edition of Chinese pharmacopoeia) and at 5, 10, 15, 20, 30 and 45min, and the following experimental results were obtained:
Figure BDA0003324983670000092
from the above experimental results, it is known that the dissolution rate of Luo Shasi can be improved by adding cyclodextrin derivative and polacrilin potassium in the embodiment of the present invention. Particularly, when the cyclodextrin derivative is selected from hydroxypropyl-beta-cyclodextrin, the dissolution effect is better; when the cyclodextrin derivative is selected from hydroxypropyl-beta-cyclodextrin, the diluent is selected from lactose and microcrystalline cellulose, and the disintegrant is selected from croscarmellose sodium, the dissolution effect is optimal. The comparative prescription 1 only limited Luo Shasi his particle size, and the comparative prescription 2 did not contain cyclodextrin derivative, the comparative prescription 3 did not contain polacrilin potassium, the particle size of roflumilast in comparative prescription 4 was 40 μm, and the comparative prescription 5 did not contain polacrilin potassium, and the dissolution effect of the prepared sample was poor when the amount of disintegrant croscarmellose sodium was increased.

Claims (11)

1. A pharmaceutical formulation of roflumilast, characterized in that it comprises Luo Shasi he, a cyclodextrin derivative, polacrilin potassium, a diluent and a disintegrant, wherein Luo Shasi his particle size d0.9 is not more than 30 μm; the cyclodextrin derivative is selected from one or more of hydroxyethyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, dihydroxypropyl-beta-cyclodextrin, methyl-beta-cyclodextrin, glucose-cyclodextrin, maltose-cyclodextrin, maltotriose-cyclodextrin and carboxymethyl-cyclodextrin; the disintegrating agent is one or more of sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crosslinked povidone and crosslinked sodium carboxymethyl cellulose; the diluent is one or more of microcrystalline cellulose, mannitol, lactose, pregelatinized starch, sucrose, sorbitol and calcium hydrophosphate.
2. A roflumilast pharmaceutical formulation according to claim 1, wherein the particle size d0.9 of Luo Shasi is 10-20 μm.
3. A roflumilast pharmaceutical formulation according to claim 1, wherein the cyclodextrin derivative is selected from hydroxypropyl- β -cyclodextrin.
4. The roflumilast pharmaceutical preparation according to claim 1, wherein the mass usage of the components of the pharmaceutical preparation is as follows: luo Shasi he 20-100 parts, cyclodextrin derivative 50-100 parts, polacrilin potassium 3-8 parts, diluent 150-250 parts and disintegrating agent 3-8 parts.
5. The roflumilast pharmaceutical preparation according to claim 1, wherein the mass usage of the components of the pharmaceutical preparation is as follows: luo Shasi he 20-100 parts, 50-100 parts of hydroxypropyl-beta-cyclodextrin, 3-8 parts of polacrilin potassium, 120-200 parts of lactose, 30-50 parts of microcrystalline cellulose and 3-8 parts of croscarmellose sodium.
6. A roflumilast pharmaceutical formulation according to claim 1, further comprising a binder and/or lubricant.
7. A roflumilast pharmaceutical formulation according to claim 6, wherein the binder is one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, povidone.
8. A roflumilast pharmaceutical preparation according to claim 6, wherein the lubricant is one or more of aerosil, talc, magnesium stearate, sodium stearyl fumarate.
9. A method of preparing the Luo Shasi pharmaceutical formulation of claim 1, comprising the steps of:
(1) Uniformly mixing roflumilast, cyclodextrin derivatives, polacrilin potassium, a diluent and a disintegrating agent to prepare a mixture;
(2) Adding purified water into the mixture obtained in the step (1), granulating, and finishing to obtain medicine particles;
(3) Tabletting the drug particles.
10. The method of claim 9, wherein the step (1) further comprises the step of adding a binder.
11. The method of claim 9, wherein the step (3) further comprises the step of uniformly mixing the drug particles with a lubricant.
CN202111264283.7A 2021-10-28 2021-10-28 Roflumilast pharmaceutical preparation Active CN113855638B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111264283.7A CN113855638B (en) 2021-10-28 2021-10-28 Roflumilast pharmaceutical preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111264283.7A CN113855638B (en) 2021-10-28 2021-10-28 Roflumilast pharmaceutical preparation

Publications (2)

Publication Number Publication Date
CN113855638A CN113855638A (en) 2021-12-31
CN113855638B true CN113855638B (en) 2023-06-09

Family

ID=78998175

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111264283.7A Active CN113855638B (en) 2021-10-28 2021-10-28 Roflumilast pharmaceutical preparation

Country Status (1)

Country Link
CN (1) CN113855638B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114848604A (en) * 2022-06-13 2022-08-05 河北戴桥医药科技有限公司 Empagliflozin and metformin hydrochloride compound preparation and preparation method thereof
CN116199628B (en) * 2023-04-28 2023-09-01 珐博进(中国)医药技术开发有限公司 Solid [ (4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl) amino ] acetic acid
CN118436652A (en) * 2024-04-18 2024-08-06 南方医科大学顺德医院(佛山市顺德区第一人民医院) Roflumilast pharmaceutical preparation and application thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104997741A (en) * 2015-06-24 2015-10-28 万特制药(海南)有限公司 Orally disintegrating tablet containing sertraline and preparation method thereof
US10500202B2 (en) * 2016-11-30 2019-12-10 Druggability Technologies Ip Holdco Limited Pharmaceutical formulation containing tadalafil
CN112315918B (en) * 2019-08-05 2022-05-17 北京福元医药股份有限公司 Ticagrelor pharmaceutical preparation
BR112022008484A2 (en) * 2019-10-31 2022-07-19 Akebia Therapeutics Inc METHOD OF TREATMENT OF ANEMIA, METHOD FOR INCREASE HEMOGLOBIN LEVELS IN A PATIENT WITH ANEMIA ASSOCIATED OR SECONDARY TO CHRONIC KIDNEY DISEASE AND METHOD FOR MAINTAINING OR CONTROLLING HEMOGLOBIN LEVELS IN A PATIENT WITH ANEMIA ASSOCIATED OR SECONDARY TO CHRONIC KIDNEY DISEASE
RU2749719C1 (en) * 2020-10-08 2021-06-16 Нестерук Владимир Викторович Drug for treatment of anemia associated with chronic kidney disease and method for its obtaining

Also Published As

Publication number Publication date
CN113855638A (en) 2021-12-31

Similar Documents

Publication Publication Date Title
CN113855638B (en) Roflumilast pharmaceutical preparation
JP5282722B2 (en) Nateglinide-containing preparation
US20090324718A1 (en) Imatinib compositions
US20220249491A1 (en) Oral solid tablet comprising bruton's tyrosine kinase inhibitor and preparation method therefor
WO2004054574A1 (en) Solid drug for oral use
JP2009109406A (en) Simultaneous determination method of ibuprofen, tipepidine, and thiamine, method of manufacturing tablet preparation ensuring effective component content using the method
JP4854158B2 (en) Formulations containing benzamide derivatives as active ingredients
CN108451909B (en) Ketorolac tromethamine tablet
KR20160105044A (en) Solid composite formulation for oral administration comprising ezetimibe and rosuvastatin
US6482417B2 (en) Stable pharmaceutical formulation comprising torsemide modification II
US20230225977A1 (en) Formulation comprising daprodustat
JP3746062B2 (en) Solid preparation and method for producing the same
RU2749719C1 (en) Drug for treatment of anemia associated with chronic kidney disease and method for its obtaining
KR20090013736A (en) Sustained-release formulation comprising metformin acid salt
JP2020183382A (en) Fingolimod hydrochloride-containing preparation and method for producing fingolimod hydrochloride-containing preparation
CN111635433A (en) Novel enol non-steroid compound and preparation method and application thereof
TWI814468B (en) Pharmaceutical composition, its preparation method and use
RU2828311C1 (en) Pharmaceutical composition, method for its preparation and use thereof
KR102585644B1 (en) Composite formulation for oral administration comprising 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4-carboxyl acid
Mude Resolving Solubility Problems and Providing an Overview of Excipients to Boost Oral Drug Bioavailability
KR20090062009A (en) Process of preparing of zaltoprofen'salt, and bioequivalent test and bioavailability analysis
WO2022125006A1 (en) High drug load compositions of favipiravir
TW201607568A (en) Pharmaceutical dosage forms comprising sodium 1-[6-(morpholin-4-yl)pyrimidin-4-yl]-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-5-olate
CN113861048A (en) Salts of nortramadol and uses thereof
KR20220014025A (en) Pharmaceutical composition comprising napamostat mesylate and dexamethasone or a salt thereof as an active ingredient

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant