CN110101676A - The preparation method of pharmaceutical intermediate pyrrolidone compound - Google Patents

The preparation method of pharmaceutical intermediate pyrrolidone compound Download PDF

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Publication number
CN110101676A
CN110101676A CN201910395048.XA CN201910395048A CN110101676A CN 110101676 A CN110101676 A CN 110101676A CN 201910395048 A CN201910395048 A CN 201910395048A CN 110101676 A CN110101676 A CN 110101676A
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parts
preparation
hydroxyethyl cellulose
cellulose
sweetener
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夏增华
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SUZHOU HEYAN BIOTECHNOLOGY Co Ltd
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SUZHOU HEYAN BIOTECHNOLOGY Co Ltd
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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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/2063—Proteins, e.g. gelatin
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives

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  • 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)
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  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention provides the preparation methods of pharmaceutical intermediate pyrrolidone compound, the following steps are included: S1: preparation prepares material, wherein preparing 0.5-1 parts of 0.5-1 parts of 0.5-2.5 parts of 5-15 parts of 55-78 parts of 9-15 parts of 3.5-18.5 parts of raw material zopiclone, hydroxyethyl cellulose, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant, the glidant that material includes following hundred number of weight；S2: main ingredient zopiclone is suspended in hydroxyethyl cellulose aqueous solution, and spray drying is recycled to form pretreatment granules of main drug；S3: sieving tabletting is made after pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant and glidant are mixed.The present invention can fater disintegration, drug effect (bioavilability) that is convenient to take, effectively improving tablet in a short time, and play a role rapidly.

Description

The preparation method of pharmaceutical intermediate pyrrolidone compound
Technical field
The present invention relates to pyrrolidone compound technical field more particularly to the systems of pharmaceutical intermediate pyrrolidone compound Preparation Method.
Background technique
The structure fragment of pyroles is prevalent in various biologically active natural products, among medical compounds, Therefore, the building or chemical modification of pyrrole derivatives cause the extensive concern of scientific research personnel.
Zopiclone is particularly suitable for not being resistant to time trouble of morning residual action for insomnia caused by a variety of causes Person is the third generation somnifacient of cyclopyrrolones, is inhibitory neurotransmitter γ-aminobutyric acid (GABA) receptor stimulating agent, Its structure and benzene phenodiazineClass is different, is Ciclopirox compound, with benzene phenodiazineClass is incorporated into identical receptor and position, but makees For different zones.Zoopery confirms that this product also has antianxiety, flesh loose and anticonvulsion in addition to hypnosis, sedation Effect, this product oral absorption is rapid, takes orally 7.5mg, Cmax 64 up to peak plasma concentrations after 1.5-2 hours after medication ~86ng/ml, oral administration biaavailability are 80 parts, and plasma protein binding rate is 45 parts.This product is distributed more widely in the tissue, distribution Volume is 100L, and by liver metabolism, main metabolites are the N- methyl zopiclone of parmacodynamics-less activity, N- oxidation product There is certain pharmacological activity, for most drugs (about 80 parts) by kidney excretion in the form of metabolin, eliminating half-life period is 5~6 Hour.
When people suffer from the medication such as insomnia, it is necessary to use taken with boiled water medicine.On the one hand, especially old when patient is taken medicine with water With women and children patient, usually it is inconvenient；On the other hand, drug is disintegrated rapidly (usual 30 seconds or less) in oral cavity, can be significantly It improves drug effect (bioavilability) and plays a role rapidly in ground.Therefore, drug oral disintegrated preparation technology has become contemporary medicine One of high-tech, it will provide very convenient and fast administration mode for all kinds of patients.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides the preparation sides of pharmaceutical intermediate pyrrolidone compound Method, the oral disintegrating tablet of the preparation method preparation of the pharmaceutical intermediate pyrrolidone compound can fater disintegration in a short time, clothes With convenience, the drug effect (bioavilability) of tablet is effectively improved, and is played a role rapidly.
To realize the above-mentioned technical purpose, the preparation method of pharmaceutical intermediate pyrrolidone compound provided by the invention, packet Include following steps:
S1: preparation prepares material, wherein preparing the raw material that material includes following hundred number of weight:
3.5-18.5 parts of zopiclone
9-15 parts of hydroxyethyl cellulose
55-78 parts of microcrystalline cellulose
5-15 parts of low-substituted hydroxypropyl cellulose
0.5-2.5 parts of sweetener
0.5-1 parts of lubricant
0.5-1 parts of glidant；
S2: main ingredient zopiclone is suspended in hydroxyethyl cellulose aqueous solution, and spray drying is recycled to form pretreatment Granules of main drug；
S3: will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant and help stream Sieving tabletting is made after agent mixes.
Further, in S1, entitled 6- (5- chloropyridine -2- base) -7- [(the 4- methyl piperazine of chemistry of the zopiclone Piperazine -1- base) carbonyloxy group] -5,6- pyrrolin [3,4-b] pyrazine -5- ketone, molecular formula C17H17ClN6O3。
Further, in S1, the sweetener is any one or two kinds in steviol glycoside, Radix Glycyrrhizae or saccharin sodium.
Further, in S1, the lubricant be one of magnesium stearate, Stepanol MG or talcum powder or Two kinds.
Further, in S1, the glidant is selected from one or both of superfine silica gel powder, talcum powder.
Further, in S2, mixed with gelatin, the weight of gelatin and hydroxyethyl cellulose in hydroxyethyl cellulose aqueous solution Than for 1:1-2:1.
In conclusion compared with prior art, the present invention having the advantage that
1. the preparation method of pharmaceutical intermediate pyrrolidone compound of the present invention, will pretreatment granules of main drug and crystallite fibre Tie up that element, low-substituted hydroxypropyl cellulose, sweetener, sieving tabletting is obtained after lubricant and glidant mix, wherein one, using straight It connects tabletting and prepares oral disintegrating tablet, simple process, energy- and time-economizing are conducive to the serialization and automated production of tablet, and cost is relatively low； Two, oral disintegrating tablet is prepared using microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hydroxyethyl cellulose, microcrystalline cellulose low takes There is stronger compressibility and disintegration for the cooperation of hydroxypropylcellulose and hydroxyethyl cellulose, can quickly collapse in a short time Solution, drug effect (bioavilability) that is convenient to take, effectively improving tablet, and play a role rapidly.
2. the preparation method of pharmaceutical intermediate pyrrolidone compound of the present invention, in hydroxyethyl cellulose aqueous solution mixed with The weight ratio of gelatin, gelatin and hydroxyethyl cellulose is 1:1-2:1, cooperates hydroxyethyl cellulose coating medicine using gelatin, and Fine texture is formed, improves drug mouthfeel, solves the problems, such as oral disintegrating tablet somehow gritty taste.
Specific embodiment
Embodiment 1:
A kind of preparation method of pharmaceutical intermediate pyrrolidone compound, comprising the following steps:
S1: preparation prepares material, wherein preparing the raw material that material includes following hundred number of weight:
3.5 parts of zopiclone
9 parts of hydroxyethyl cellulose
55 parts of microcrystalline cellulose
5 parts of low-substituted hydroxypropyl cellulose
0.5 part of sweetener
0.5 part of lubricant
0.5 part of glidant；
Wherein, entitled 6- (5- chloropyridine -2- base) -7- [(4- methylpiperazine-1-yl) carbonyl oxygen of chemistry of the zopiclone Base] -5,6- pyrrolin [3,4-b] pyrazine -5- ketone, molecular formula C17H17ClN6O3；
Wherein, the sweetener is steviol glycoside；
Wherein, the lubricant is magnesium stearate；
Wherein, the glidant is selected from superfine silica gel powder；
S2: main ingredient zopiclone is suspended in hydroxyethyl cellulose aqueous solution, and spray drying is recycled to form pretreatment Granules of main drug；
Wherein, in hydroxyethyl cellulose aqueous solution mixed with gelatin, the weight ratio of gelatin and hydroxyethyl cellulose is 1:1；
S3: will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant and help stream Sieving tabletting is made after agent mixes.
Using above-mentioned technology, will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, Sieving tabletting is made after lubricant and glidant mix, wherein one, oral disintegrating tablet, simple process, energy conservation are prepared using direct tablet compressing It is time saving, be conducive to the serialization and automated production of tablet, cost is relatively low；Two, using microcrystalline cellulose, low-substituted hydroxypropyl fiber Element and hydroxyethyl cellulose prepare oral disintegrating tablet, the cooperation of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hydroxyethyl cellulose With stronger compressibility and disintegration, can fater disintegration in a short time, drug effect that is convenient to take, effectively improving tablet (bioavilability), and play a role rapidly.
In addition, cooperate hydroxyethyl cellulose coating medicine using gelatin mixed with gelatin in its hydroxyethyl cellulose aqueous solution, And fine texture is formed, improve drug mouthfeel, solves the problems, such as oral disintegrating tablet somehow gritty taste.
Embodiment 2:
A kind of preparation method of pharmaceutical intermediate pyrrolidone compound, comprising the following steps:
S1: preparation prepares material, wherein preparing the raw material that material includes following hundred number of weight:
6.5 parts of zopiclone
10 parts of hydroxyethyl cellulose
58 parts of microcrystalline cellulose
8 parts of low-substituted hydroxypropyl cellulose
0.9 part of sweetener
0.6 part of lubricant
0.6 part of glidant；
Wherein, entitled 6- (5- chloropyridine -2- base) -7- [(4- methylpiperazine-1-yl) carbonyl oxygen of chemistry of the zopiclone Base] -5,6- pyrrolin [3,4-b] pyrazine -5- ketone, molecular formula C17H17ClN6O3；
Wherein, the sweetener is any one in steviol glycoside, Radix Glycyrrhizae or saccharin sodium or two kinds；
Wherein, the lubricant is one or both of magnesium stearate, Stepanol MG or talcum powder；
Wherein, the glidant is selected from one or both of superfine silica gel powder, talcum powder；
S2: main ingredient zopiclone is suspended in hydroxyethyl cellulose aqueous solution, and spray drying is recycled to form pretreatment Granules of main drug；
Wherein, in hydroxyethyl cellulose aqueous solution mixed with gelatin, the weight ratio of gelatin and hydroxyethyl cellulose is 1:1；
S3: will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant and help stream Sieving tabletting is made after agent mixes.
Using above-mentioned technology, will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, Sieving tabletting is made after lubricant and glidant mix, wherein one, oral disintegrating tablet, simple process, energy conservation are prepared using direct tablet compressing It is time saving, be conducive to the serialization and automated production of tablet, cost is relatively low；Two, using microcrystalline cellulose, low-substituted hydroxypropyl fiber Element and hydroxyethyl cellulose prepare oral disintegrating tablet, the cooperation of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hydroxyethyl cellulose With stronger compressibility and disintegration, can fater disintegration in a short time, drug effect that is convenient to take, effectively improving tablet (bioavilability), and play a role rapidly.
In addition, cooperate hydroxyethyl cellulose coating medicine using gelatin mixed with gelatin in its hydroxyethyl cellulose aqueous solution, And fine texture is formed, improve drug mouthfeel, solves the problems, such as oral disintegrating tablet somehow gritty taste.
Embodiment 3:
A kind of preparation method of pharmaceutical intermediate pyrrolidone compound, comprising the following steps:
S1: preparation prepares material, wherein preparing the raw material that material includes following hundred number of weight:
10.5 parts of zopiclone
11 parts of hydroxyethyl cellulose
63 parts of microcrystalline cellulose
10 parts of low-substituted hydroxypropyl cellulose
1.3 parts of sweetener
0.7 part of lubricant
0.7 part of glidant；
Wherein, entitled 6- (5- chloropyridine -2- base) -7- [(4- methylpiperazine-1-yl) carbonyl oxygen of chemistry of the zopiclone Base] -5,6- pyrrolin [3,4-b] pyrazine -5- ketone, molecular formula C17H17ClN6O3；
Wherein, the sweetener is any one in steviol glycoside, Radix Glycyrrhizae or saccharin sodium or two kinds；
Wherein, the lubricant is one or both of magnesium stearate, Stepanol MG or talcum powder；
Wherein, the glidant is selected from one or both of superfine silica gel powder, talcum powder；
S2: main ingredient zopiclone is suspended in hydroxyethyl cellulose aqueous solution, and spray drying is recycled to form pretreatment Granules of main drug；
Wherein, in hydroxyethyl cellulose aqueous solution mixed with gelatin, the weight ratio of gelatin and hydroxyethyl cellulose is 1:1；
S3: will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant and help stream Sieving tabletting is made after agent mixes.
Using above-mentioned technology, will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, Sieving tabletting is made after lubricant and glidant mix, wherein one, oral disintegrating tablet, simple process, energy conservation are prepared using direct tablet compressing It is time saving, be conducive to the serialization and automated production of tablet, cost is relatively low；Two, using microcrystalline cellulose, low-substituted hydroxypropyl fiber Element and hydroxyethyl cellulose prepare oral disintegrating tablet, the cooperation of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hydroxyethyl cellulose With stronger compressibility and disintegration, can fater disintegration in a short time, drug effect that is convenient to take, effectively improving tablet (bioavilability), and play a role rapidly.
In addition, cooperate hydroxyethyl cellulose coating medicine using gelatin mixed with gelatin in its hydroxyethyl cellulose aqueous solution, And fine texture is formed, improve drug mouthfeel, solves the problems, such as oral disintegrating tablet somehow gritty taste.
Embodiment 4:
A kind of preparation method of pharmaceutical intermediate pyrrolidone compound, comprising the following steps:
S1: preparation prepares material, wherein preparing the raw material that material includes following hundred number of weight:
13.5 parts of zopiclone
13 parts of hydroxyethyl cellulose
67 parts of microcrystalline cellulose
12 parts of low-substituted hydroxypropyl cellulose
1.6 parts of sweetener
0.8 part of lubricant
0.8 part of glidant；
Wherein, entitled 6- (5- chloropyridine -2- base) -7- [(4- methylpiperazine-1-yl) carbonyl oxygen of chemistry of the zopiclone Base] -5,6- pyrrolin [3,4-b] pyrazine -5- ketone, molecular formula C17H17ClN6O3；
Wherein, the sweetener is any one in steviol glycoside, Radix Glycyrrhizae or saccharin sodium or two kinds；
Wherein, the lubricant is one or both of magnesium stearate, Stepanol MG or talcum powder；
Wherein, the glidant is selected from one or both of superfine silica gel powder, talcum powder；
S2: main ingredient zopiclone is suspended in hydroxyethyl cellulose aqueous solution, and spray drying is recycled to form pretreatment Granules of main drug；
Wherein, in hydroxyethyl cellulose aqueous solution mixed with gelatin, the weight ratio of gelatin and hydroxyethyl cellulose is 2:1；
S3: will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant and help stream Sieving tabletting is made after agent mixes.
Using above-mentioned technology, will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, Sieving tabletting is made after lubricant and glidant mix, wherein one, oral disintegrating tablet, simple process, energy conservation are prepared using direct tablet compressing It is time saving, be conducive to the serialization and automated production of tablet, cost is relatively low；Two, using microcrystalline cellulose, low-substituted hydroxypropyl fiber Element and hydroxyethyl cellulose prepare oral disintegrating tablet, the cooperation of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hydroxyethyl cellulose With stronger compressibility and disintegration, can fater disintegration in a short time, drug effect that is convenient to take, effectively improving tablet (bioavilability), and play a role rapidly.
In addition, cooperate hydroxyethyl cellulose coating medicine using gelatin mixed with gelatin in its hydroxyethyl cellulose aqueous solution, And fine texture is formed, improve drug mouthfeel, solves the problems, such as oral disintegrating tablet somehow gritty taste.
Embodiment 5:
A kind of preparation method of pharmaceutical intermediate pyrrolidone compound, comprising the following steps:
S1: preparation prepares material, wherein preparing the raw material that material includes following hundred number of weight:
15.5 parts of zopiclone
14 parts of hydroxyethyl cellulose
73 parts of microcrystalline cellulose
14 parts of low-substituted hydroxypropyl cellulose
2.2 parts of sweetener
0.9 part of lubricant
0.9 part of glidant；
Wherein, entitled 6- (5- chloropyridine -2- base) -7- [(4- methylpiperazine-1-yl) carbonyl oxygen of chemistry of the zopiclone Base] -5,6- pyrrolin [3,4-b] pyrazine -5- ketone, molecular formula C17H17ClN6O3；
Wherein, the sweetener is any one in steviol glycoside, Radix Glycyrrhizae or saccharin sodium or two kinds；
Wherein, the lubricant is one or both of magnesium stearate, Stepanol MG or talcum powder；
Wherein, the glidant is selected from one or both of superfine silica gel powder, talcum powder；
S2: main ingredient zopiclone is suspended in hydroxyethyl cellulose aqueous solution, and spray drying is recycled to form pretreatment Granules of main drug；
Wherein, in hydroxyethyl cellulose aqueous solution mixed with gelatin, the weight ratio of gelatin and hydroxyethyl cellulose is 2:1；
S3: will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant and help stream Sieving tabletting is made after agent mixes.
Using above-mentioned technology, will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, Sieving tabletting is made after lubricant and glidant mix, wherein one, oral disintegrating tablet, simple process, energy conservation are prepared using direct tablet compressing It is time saving, be conducive to the serialization and automated production of tablet, cost is relatively low；Two, using microcrystalline cellulose, low-substituted hydroxypropyl fiber Element and hydroxyethyl cellulose prepare oral disintegrating tablet, the cooperation of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hydroxyethyl cellulose With stronger compressibility and disintegration, can fater disintegration in a short time, drug effect that is convenient to take, effectively improving tablet (bioavilability), and play a role rapidly.
In addition, cooperate hydroxyethyl cellulose coating medicine using gelatin mixed with gelatin in its hydroxyethyl cellulose aqueous solution, And fine texture is formed, improve drug mouthfeel, solves the problems, such as oral disintegrating tablet somehow gritty taste.
Embodiment 6:
A kind of preparation method of pharmaceutical intermediate pyrrolidone compound, comprising the following steps:
S1: preparation prepares material, wherein preparing the raw material that material includes following hundred number of weight:
18.5 parts of zopiclone
15 parts of hydroxyethyl cellulose
78 parts of microcrystalline cellulose
15 parts of low-substituted hydroxypropyl cellulose
2.5 parts of sweetener
1 part of lubricant
1 part of glidant；
Wherein, entitled 6- (5- chloropyridine -2- base) -7- [(4- methylpiperazine-1-yl) carbonyl oxygen of chemistry of the zopiclone Base] -5,6- pyrrolin [3,4-b] pyrazine -5- ketone, molecular formula C17H17ClN6O3；
Wherein, the sweetener is any one in steviol glycoside, Radix Glycyrrhizae or saccharin sodium or two kinds；
Wherein, the lubricant is one or both of magnesium stearate, Stepanol MG or talcum powder；
Wherein, the glidant is selected from one or both of superfine silica gel powder, talcum powder；
S2: main ingredient zopiclone is suspended in hydroxyethyl cellulose aqueous solution, and spray drying is recycled to form pretreatment Granules of main drug；
Wherein, in hydroxyethyl cellulose aqueous solution mixed with gelatin, the weight ratio of gelatin and hydroxyethyl cellulose is 2:1；
S3: will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant and help stream Sieving tabletting is made after agent mixes.
Using above-mentioned technology, will pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, Sieving tabletting is made after lubricant and glidant mix, wherein one, oral disintegrating tablet, simple process, energy conservation are prepared using direct tablet compressing It is time saving, be conducive to the serialization and automated production of tablet, cost is relatively low；Two, using microcrystalline cellulose, low-substituted hydroxypropyl fiber Element and hydroxyethyl cellulose prepare oral disintegrating tablet, the cooperation of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hydroxyethyl cellulose With stronger compressibility and disintegration, can fater disintegration in a short time, drug effect that is convenient to take, effectively improving tablet (bioavilability), and play a role rapidly.
In addition, cooperate hydroxyethyl cellulose coating medicine using gelatin mixed with gelatin in its hydroxyethyl cellulose aqueous solution, And fine texture is formed, improve drug mouthfeel, solves the problems, such as oral disintegrating tablet somehow gritty taste.
The above is only a preferred embodiment of the present invention, protection scope of the present invention is not limited merely to above-mentioned implementation Example, all technical solutions belonged under thinking of the present invention all belong to the scope of protection of the present invention.It should be pointed out that for the art Those of ordinary skill for, several improvements and modifications without departing from the principles of the present invention, these improvements and modifications It should be regarded as protection scope of the present invention.

Claims (6)

1. a kind of preparation method of pharmaceutical intermediate pyrrolidone compound, which is characterized in that include the following steps
S1: preparation prepares material, wherein preparing the raw material that material includes following hundred number of weight:
3.5-18.5 parts of zopiclone
9-15 parts of hydroxyethyl cellulose
55-78 parts of microcrystalline cellulose
5-15 parts of low-substituted hydroxypropyl cellulose
0.5-2.5 parts of sweetener
0.5-1 parts of lubricant
0.5-1 parts of glidant；
S2: main ingredient zopiclone is suspended in hydroxyethyl cellulose aqueous solution, and spray drying is recycled to form pretreatment main ingredient Particle；
S3: pretreatment granules of main drug and microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sweetener, lubricant and glidant are mixed Sieving tabletting is made after even.
2. the production method of the preparation method of pharmaceutical intermediate pyrrolidone compound according to claim 1, feature It is, in S1, entitled 6- (5- chloropyridine -2- base) -7- [(4- methylpiperazine-1-yl) carbonyl oxygen of chemistry of the zopiclone Base] -5,6- pyrrolin [3,4-b] pyrazine -5- ketone, molecular formula C17H17ClN6O3。
3. the production method of the preparation method of pharmaceutical intermediate pyrrolidone compound according to claim 1, feature It is, in S1, the sweetener is any one or two kinds in steviol glycoside, Radix Glycyrrhizae or saccharin sodium.
4. the production method of the preparation method of pharmaceutical intermediate pyrrolidone compound according to claim 1, feature It is, in S1, the lubricant is one or both of magnesium stearate, Stepanol MG or talcum powder.
5. the production method of the preparation method of pharmaceutical intermediate pyrrolidone compound according to claim 1, feature It is, in S1, the glidant is selected from one or both of superfine silica gel powder, talcum powder.
6. the production method of the preparation method of pharmaceutical intermediate pyrrolidone compound according to claim 1, feature It is, in S2, mixed with gelatin in hydroxyethyl cellulose aqueous solution, the weight ratio of gelatin and hydroxyethyl cellulose is 1:1-2:1.
CN201910395048.XA 2019-05-13 2019-05-13 The preparation method of pharmaceutical intermediate pyrrolidone compound Pending CN110101676A (en)

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