CN110934846A - Adelalcidol capsule and preparation method thereof - Google Patents

Adelalcidol capsule and preparation method thereof Download PDF

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Publication number
CN110934846A
CN110934846A CN201911265064.3A CN201911265064A CN110934846A CN 110934846 A CN110934846 A CN 110934846A CN 201911265064 A CN201911265064 A CN 201911265064A CN 110934846 A CN110934846 A CN 110934846A
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eldecalcitol
parts
capsule
surfactant
diluent
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CN201911265064.3A
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Chinese (zh)
Inventor
刘晓霞
陈阳生
袁航
孙桂玉
臧云龙
杜昌余
牛建兴
曲胜军
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CP Pharmaceutical Qingdao Co Ltd
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CP Pharmaceutical Qingdao Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • 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
    • A61K9/4858—Organic 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Nutrition Science (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses an adicalcitol capsule and a preparation method thereof. The eldecalcitol capsule comprises: the composition comprises the eldecalcitol and preparation auxiliary materials, wherein the preparation auxiliary materials comprise a filling agent, a disintegrating agent, a surfactant, a diluent and a lubricant. The inventive aldecalcitol capsule has the advantages of rapid dissolution, fast absorption, high bioavailability, good stability, convenient administration, etc.

Description

Adelalcidol capsule and preparation method thereof
Technical Field
The invention relates to a capsule, in particular to an eldecalcitol capsule and a preparation method thereof, belonging to the field of eldecalcitol capsules.
Background
Eldecalcitol, known by the english name Eldecalcitol, is a white crystalline powder, sensitive to light and air. Slightly soluble in methanol, ethanol and ethyl acetate. It is one of the most important metabolic active products of vitamin D3 in human body, and has the functions of promoting the absorption of calcium by small intestine and regulating the transport of inorganic salt in bone; is mainly used for osteoporosis; renal osteodystrophy in chronic renal failure patients, particularly patients requiring long-term hemodialysis; spontaneous and pseudo-hypoparathyroidism following surgery; vitamin D3 dependent rickets and vitamin D resistant rickets with hypophosphatemia; skin diseases such as psoriasis; and other vitamin D deficiencies. The calcitriol is fast to absorb orally, the peak is reached in 3-6 hours, t1/2 is about 3-6 hours, the urine calcium concentration is increased after 7 hours, and the single oral dose can continue the pharmacological activity for 3-5 days.
At present, the main preparation forms of the eldecalcitol are soft capsules and injection; the preparation formulation is monotonous, the eldercalciferol is sensitive to light and air, the solubility of common organic solvents is low, the stability of soft capsules and injection is poor, the content of active ingredients is extremely low, and the bioavailability is low.
The capsule can cover up the unpleasant odor of the medicine and is easy to swallow; can improve the stability and bioavailability of the medicine; can also release the medicine in fixed time and fixed position, can make up the defects of other solid dosage forms, and has wide application.
Disclosure of Invention
The invention provides an eldecalcitol capsule which has short disintegration time and rapid drug dissolution.
The present invention provides a method for preparing the said abdocalcitol capsule.
The above object of the present invention is achieved by the following technical solutions:
an eldecalcitol capsule comprising: the preparation comprises the components of eldecalcitol and preparation auxiliary materials; the preparation auxiliary materials comprise: filler, disintegrant, surfactant, diluent, and lubricant.
The dosage of each component is preferably as follows according to the weight portion: 0.1-1 part of elderberry, 70-75 parts of filler, 10-20 parts of disintegrant, 0.5-2 parts of surfactant, 2-10 parts of diluent and 1-4 parts of lubricant; more preferably, the amount of each component is: 0.5 part of eldecalcitol, 73 parts of filler, 15 parts of disintegrant, 1.5 parts of surfactant, 8 parts of diluent and 2 parts of lubricant.
Preferably, the disintegrant is sodium carboxymethyl starch, polyvinylpyrrolidone, sodium glycolate or microcrystalline cellulose.
The surfactant is preferably sodium dodecyl sulfate, polysorbate-80, poloxamer, polyethylene glycol caprylic glyceride, polyethylene glycol capric glyceride, polyethylene glycol lauric glyceride or polyethylene glycol stearic glyceride.
The filler may be lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine.
The diluent is lactose or pregelatinized starch; the lubricant is magnesium stearate or talcum powder.
Experiments show that the ratio of the disintegrant to the surfactant has a very significant influence on the dissolution rate of the medicament, wherein the dissolution rate of the medicament is the fastest and the bioavailability is the highest when the disintegrant and the surfactant are mixed according to the weight ratio of 15: 1.5.
Another technical problem underlying the present invention is to provide a method for preparing said eldecalcitol capsules comprising the following steps: uniformly mixing the eldecalcitol, the filler, the disintegrant, the surfactant, the diluent and the lubricant; pulverizing, sieving, granulating, and making into capsule.
The inventive aldecalcitol capsule has the advantages of rapid dissolution, fast absorption, high bioavailability, good stability, convenient administration, etc.
Detailed Description
Example 1
Weighing the following components in percentage by weight:
0.5 percent of alditol
16 percent of corn starch
Sodium carboxymethyl starch 12%
1.5 percent of polyethylene glycol lauric glyceride
Lactose 8%
Magnesium stearate 2%
The preparation process comprises the following steps:
(1) weighing the main raw material drug of the eldecalcitol according to the proportion of 0.5 percent, and sieving the main raw material drug with a 80-mesh sieve for later use;
(2) respectively and progressively increasing and uniformly mixing the eldecalcitol raw material medicine with 16% of corn starch, 12% of sodium carboxymethyl starch and 1.5% of polyethylene glycol lauric glyceride in an equivalent manner;
(3) mixing the mixture with 8% lactose, adding 2% magnesium stearate, and mixing for 2 min;
(4) sieving with 18 mesh sieve, grading, and encapsulating to obtain the final product.
Example 2
Weighing the following components in percentage by weight:
0.5 percent of alditol
71 percent of corn starch
Sodium carboxymethyl starch 17%
1.5 percent of polyethylene glycol lauric glyceride
Lactose 8%
Magnesium stearate 2%
The preparation process is the same as in example 1.
Example 3
Weighing the following components in percentage by weight:
0.5 percent of alditol
72 percent of corn starch
Sodium carboxymethyl starch 16%
1.5 percent of polyethylene glycol lauric glyceride
Lactose 8%
Magnesium stearate 2%
The preparation process is the same as in example 1.
Example 4
Weighing the following components in percentage by weight:
0.5 percent of alditol
Corn starch 75%
Sodium carboxymethyl starch 13%
1.5 percent of polyethylene glycol lauric glyceride
Lactose 8%
Magnesium stearate 2%
The preparation process is the same as in example 1.
Example 5
Weighing the following components in percentage by weight:
0.5 percent of alditol
Corn starch 74%
Sodium carboxymethyl starch 14%
1.5 percent of polyethylene glycol lauric glyceride
Lactose 8%
Magnesium stearate 2%
The preparation process is the same as in example 1.
Example 6
Weighing the following components in percentage by weight:
0.5 percent of alditol
Corn starch 73%
Sodium carboxymethyl starch 15%
1.5 percent of polyethylene glycol lauric glyceride
Lactose 8%
Magnesium stearate 2%
The preparation process is the same as in example 1.
Test example 1 Long-term stability test
The sample to be put on the market is placed at the temperature of 25 ℃ and the relative humidity of 60 percent for 36 months, and is sampled and measured by high performance liquid chromatography (0512 in the four-part general regulation of the 2015 edition) at the time of 0, 3, 6, 12, 24 and 36 months respectively, and acetonitrile-water (75: 25) is taken as a mobile phase; the detection wavelength is 265nm, the number of theoretical plates is not less than 5000 according to the peak calculation of the main component, the detection wavelength is obtained by calculating the peak area according to an external standard method, and the test result shows that: the inventive abdocalcitol capsule of example 6 was stable and reliable. The results are shown in the following table:
Figure DEST_PATH_IMAGE001

Claims (7)

1. an eldecalcitol capsule, comprising: the preparation comprises the components of eldecalcitol and preparation auxiliary materials; the preparation auxiliary materials comprise: filler, disintegrant, surfactant, diluent, and lubricant.
2. The eldecalcitol capsule according to claim 1, wherein the amount of each ingredient is, in parts by weight:
0.1-1 part of alditol
70-75 parts of filler
10-20 parts of disintegrating agent
0.5-2 parts of surfactant
2-10 parts of diluent
1-5 parts of a lubricant.
3. The eldecalcitol capsule according to claim 2, wherein the amounts of the ingredients are:
0.5 part of digalciferol
73 parts of filler
15 portions of disintegrating agent
Surfactant 1.5 parts
8 portions of diluent
And 2 parts of a lubricant.
4. The eldecalcitol capsule according to claims 1 to 3, characterized in that: the disintegrating agent is selected from one or more of sodium carboxymethyl starch, polyvinylpyrrolidone, sodium glycolate or microcrystalline cellulose.
5. The eldecalcitol capsule according to claims 1 to 3, characterized in that: the surfactant is sodium dodecyl sulfate, polysorbate-80, poloxamer, polyethylene glycol caprylic glyceride, polyethylene glycol capric glyceride, polyethylene glycol lauric glyceride or polyethylene glycol stearic glyceride.
6. The eldecalcitol capsule according to claims 1 to 3, characterized in that: the filler is lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine; the diluent is lactose or pregelatinized starch; the lubricant is magnesium stearate or talcum powder.
7. A method of an abdocalcitol capsule according to claims 1-3, comprising the steps of: uniformly mixing the eldecalcitol, the filler, the disintegrant, the surfactant, the diluent and the lubricant; pulverizing, sieving, granulating, and making into capsule.
CN201911265064.3A 2019-12-11 2019-12-11 Adelalcidol capsule and preparation method thereof Withdrawn CN110934846A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114053286A (en) * 2021-12-08 2022-02-18 博凯药业有限公司 Pharmaceutical composition and preparation method and application thereof
CN115266994A (en) * 2022-08-02 2022-11-01 人福普克药业（武汉）有限公司 Method for detecting content of eldecalcitol by high performance liquid chromatography
CN115531329A (en) * 2021-12-23 2022-12-30 南京海融制药有限公司 Stable eldecalcitol tablet

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103110606A (en) * 2013-02-19 2013-05-22 青岛正大海尔制药有限公司 Alfacalcidol capsules and preparation method thereof
CN108420797A (en) * 2018-05-09 2018-08-21 南京海融制药有限公司 Novel vitamin D analogues preparation and preparation method thereof
JP2019014676A (en) * 2017-07-06 2019-01-31 東海カプセル株式会社 Capsule agent
CN110478330A (en) * 2019-09-29 2019-11-22 河南泰丰生物科技有限公司 A kind of Chinese mugwort ground ossification alcohol soft capasule and preparation method thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103110606A (en) * 2013-02-19 2013-05-22 青岛正大海尔制药有限公司 Alfacalcidol capsules and preparation method thereof
JP2019014676A (en) * 2017-07-06 2019-01-31 東海カプセル株式会社 Capsule agent
CN108420797A (en) * 2018-05-09 2018-08-21 南京海融制药有限公司 Novel vitamin D analogues preparation and preparation method thereof
CN110478330A (en) * 2019-09-29 2019-11-22 河南泰丰生物科技有限公司 A kind of Chinese mugwort ground ossification alcohol soft capasule and preparation method thereof

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114053286A (en) * 2021-12-08 2022-02-18 博凯药业有限公司 Pharmaceutical composition and preparation method and application thereof
CN114053286B (en) * 2021-12-08 2023-09-19 博凯药业有限公司 Pharmaceutical composition and preparation method and application thereof
CN115531329A (en) * 2021-12-23 2022-12-30 南京海融制药有限公司 Stable eldecalcitol tablet
CN115531329B (en) * 2021-12-23 2024-01-30 南京海融制药有限公司 Stable idecalcitol tablet
CN115266994A (en) * 2022-08-02 2022-11-01 人福普克药业（武汉）有限公司 Method for detecting content of eldecalcitol by high performance liquid chromatography

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