CN110393707A - Dextrorotation Oxiracetam enteric coatel tablets and preparation method thereof - Google Patents
Dextrorotation Oxiracetam enteric coatel tablets and preparation method thereof Download PDFInfo
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- CN110393707A CN110393707A CN201810960824.1A CN201810960824A CN110393707A CN 110393707 A CN110393707 A CN 110393707A CN 201810960824 A CN201810960824 A CN 201810960824A CN 110393707 A CN110393707 A CN 110393707A
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- dextrorotation oxiracetam
- coatel tablets
- enteric coatel
- dextrorotation
- oxiracetam
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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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The present invention provides a kind of dextrorotation Oxiracetam enteric coatel tablets, include 55~80% crystal form dextrorotation Oxiracetam, 5~25% fillers, 5-10% sodium carboxymethyl starch, 3-10% low-substituted hydroxypropyl cellulose, 1-5% lubricant, the enteric material of 5-12%, by percentage to the quality.Dextrorotation Oxiracetam enteric coatel tablets of the present invention list under terms of packing in simulation, after being placed 6 months under the conditions of temperature 60 C ± 2 DEG C, relative humidity are 35% ± 5%, every quality detecting index is without significant changes, show that dextrorotation Oxiracetam enteric coatel tablets of the present invention are stable and controllable for quality, clinical use is safer and more effective.Preparation method of the present invention is simple, is suitble to industrialized production.
Description
Technical field
The present invention relates to dextrorotation oxiracetam preparations, and in particular to a kind of dextrorotation Oxiracetam enteric coatel tablets and its preparation side
Method.
Background technique
Oxiracetam (Oxiracetam), chemical name are Esomeprazole, are big by anticipating
Sharp ISF S.P.A company researches and develops synthesis first, is clinically widely used in light moderate vascular dementia, senile dementia and various
The diseases such as cerebrovascular disease, cerebral injury, intracranial infection, curative for effect, safety is good.Studies have shown that the chiral isomer of Oxiracetam
Dextrorotation Oxiracetam has preferable activity in terms of anti-epileptic, especially as treatment epilepsy generalized seizures, epilepsy part
Property breaking-out and status epilepticus drug effect it is obvious, be expected to exploitation at novel low-toxicity antiepileptic.Chinese patent
CN101766596A disclose it is a kind of using dextrorotation Oxiracetam as the solid pharmaceutical preparation of active constituent, it includes dextrorotation Oxiracetam and
Pharmaceutically acceptable auxiliary material, this method effectively reduce the toxic side effect of Oxiracetam.It is found after researching and analysing, above-mentioned public affairs
The dextrorotation Oxiracetam solid pharmaceutical preparation product active ingredient opened mainly dissolves out under one's belt, with the extension of residence time in stomach, by
Gastric acid influences and drug is caused to decompose, so that pharmaceutical activity reduces, and is unfavorable for guaranteeing clinical application safety.
Summary of the invention
In order to overcome the drawbacks of the prior art, the present invention provides a kind of crystal form dextrorotation Oxiracetam.
To achieve the purpose of the present invention, the present invention uses following technical scheme.
In dextrorotation Oxiracetam enteric coatel tablets of the present invention comprising 55~80% crystal form dextrorotation Oxiracetam, 5
~25% filler, 5-10% sodium carboxymethyl starch, 3-10% low-substituted hydroxypropyl cellulose, 1-5% lubricant, the intestines of 5-12%
Molten material, by percentage to the quality.
The dextrorotation Oxiracetam of crystal form of the present invention is radiated using Cu-K α, obtained X-ray powder diffraction
Spectrum is 16.66 ± 0.2 °, 17.54 ± 0.2 °, 19.42 ± 0.2 °, 21 ± 0.2 °, 22.16 ± 0.2 °, 23.46 in 2 θ of angle of reflection
There is diffraction maximum at ± 0.2 °, 25.36 ± 0.2 °, 26.08 ± 0.2 °, 30.96 ± 0.2 °.
In dextrorotation Oxiracetam enteric coatel tablets of the present invention comprising 60~75% crystal form dextrorotation Oxiracetam, 5
~20% filler, 5-10% sodium carboxymethyl starch, 3-10% low-substituted hydroxypropyl cellulose, 1-3% lubricant, the intestines of 5-10%
Molten material, by percentage to the quality.
Filler of the present invention is selected from microcrystalline cellulose, lactose, mannitol, sorbierite, amylum pregelatinisatum, dextrin, sugarcane
At least one of sugar, calcium phosphate dibasic anhydrous；Preferably microcrystalline cellulose, lactose, mannitol, sorbierite, sucrose are at least one.This hair
The bright lubricant in magnesium stearate, calcium stearate, zinc stearate, polyethylene glycol, talcum powder and superfine silica gel powder at least
It is a kind of；The enteric-coating material be selected from acetate fiber phthalate ester, methacrylic acid copolymer, cellulose acetate benzenetricarboxylic acid ester and
At least one of hydroxypropyl cellulose phthalate ester.
The mass ratio of sodium carboxymethyl starch and low-substituted hydroxypropyl cellulose of the present invention is 1~2:1.
In dextrorotation Oxiracetam enteric coatel tablets of the present invention comprising 60~75% crystal form dextrorotation Oxiracetam, 5
~20% lactose, 5-10% sodium carboxymethyl starch, 3-10% low-substituted hydroxypropyl cellulose, 1-3% superfine silica gel powder, the vinegar of 5-10%
Acid cellulose benzenetricarboxylic acid ester, by percentage to the quality；The mass ratio of the sodium carboxymethyl starch and low-substituted hydroxypropyl cellulose is 1
~2:1.
The dextrorotation Oxiracetam of crystal form of the present invention is made with the following method: with dioxane that dextrorotation is difficult to understand
La Xitan is sealed with concentration 10mg/mL-40mg/mL dissolution, is the 20-30 DEG C of speed with 150-300r/min in temperature
20-25h is stirred, it is 50-75 DEG C in temperature that filtrate is stood volatilization crystallization, collects crystal by filtering, relative humidity 15-30%
Under conditions of dry 4-7h, both.
Label is made by dry granulation tabletting, then piece in the preparation method of dextrorotation Oxiracetam enteric coatel tablets of the present invention
Enteric coatel tablets are made in core enteric coating, it is characterised in that: the label is made by following steps: by crystal form dextrorotation Oxiracetam
It is sieved with other auxiliary materials, is added in dry granulating machine and pelletizes, control 8~15MPa of hydraulic system pressure of dry granulating machine,
Host speed regulation≤22Hz, 7~12Hz of straight feeding frequency, 7~15Hz of vertical feeding frequency crushed 60 meshes；By gained
Grain is cooled to 20 DEG C after 50-75 DEG C of dry 30~60min and dextrorotation Oxiracetam particle is made with bottom discharge, and lubrication is then added
Agent mixes, and label is made in tabletting.
The preparation method of dextrorotation Oxiracetam enteric coatel tablets of the present invention, which comprises the steps of:
(1) crystal form dextrorotation Oxiracetam is prepared: with dioxane by dextrorotation Oxiracetam with concentration 10mg/mL-
40mg/mL dissolution, seals, and is that the 20-30 DEG C of speed with 150-300r/min stirs 20-25h in temperature, filtering will filter
Liquid stands volatilization crystallization, collects crystal, is 50-75 DEG C in temperature, relative humidity dry 4-7h under conditions of being 15-30%, both
Obtain crystal form dextrorotation Oxiracetam；
(2) dry granulation prepares label: crystal form dextrorotation Oxiracetam and other auxiliary materials being sieved, dry granulation is added
It pelletizes in machine, controls 8~15MPa of hydraulic system pressure of dry granulating machine, host speed regulation≤22Hz, straight feeding frequency
7~12Hz, 7~15Hz of vertical feeding frequency, crushed 60 meshes；Gained particle is dropped after 50-75 DEG C of dry 30~60min
Dextrorotation Oxiracetam particle is made to 20 DEG C with bottom discharge in temperature, and lubricant is then added and mixes, label is made in tabletting；
(3) enteric coating: and then label is placed in coating pan, preheating starts to spray into coating pan dense after 15~30 minutes
The enteric-coating material ethanol solution that degree is 75~85%, while blowing hot-air, the revolving speed 10-15rpm of coating pan, inlet air temperature are
30~40 DEG C, when weight gain 8~12%, stops coating, be dried to obtain dextrorotation Oxiracetam enteric coatel tablets of the present invention.
The utility model has the advantages that
The present invention provides a kind of dextrorotation Oxiracetam enteric coatel tablets, the enteric coatel tablets are with specific crystal form dextrorotation Aura west
Smooth is active constituent, and then with specific auxiliary material through dry granulation, enteric coating is made, and active constituent is dispersed in carrier material
In, so that dextrorotation Oxiracetam is formed hydrophilic gel in intestinal juice, drugloading rate is high, while dextrorotation Oxiracetam and intestines during release
Mucous membrane exposure concentration is small, and drug releasing rate is gently lasting, to significantly improve curative effect of medication and bioavilability, and reaches
The effect of controlled release to a certain degree is arrived.Dextrorotation Oxiracetam enteric coatel tablets preparation process stable crystal form of the present invention, is conducive to ensure it
The efficacy and saferry of pharmaceutical preparation in clinical application；Dextrorotation Oxiracetam enteric coatel tablets of the present invention are due to using dextrorotation
Oxiracetam crystal form is accelerated in the intracorporal absorption of people, improves bioavilability, to improve curative effect, improves unit dose
The service efficiency of amount preferentially and the selection that has provided of clinical application for Hospital Drugs has very high economic and society
Meaning.Dextrorotation Oxiracetam enteric coatel tablets of the present invention simulation list terms of packing under, be in 40 DEG C ± 2 DEG C of temperature, relative humidity
After placing 6 months under the conditions of 35% ± 5%, every quality detecting index shows that dextrorotation of the present invention is difficult to understand without significant changes
La Xitan enteric coatel tablets are stable and controllable for quality, and clinical use is safer and more effective.Preparation method of the present invention is simple, is suitble to industry metaplasia
It produces.
Specific embodiment
The present invention is specifically described below by embodiment, it is necessary to which indicated herein is that following embodiment is only used
In invention is further explained, it should not be understood as limiting the scope of the invention, person skilled in art can
To make some nonessential modifications and adaptations to the present invention according to aforementioned present invention content.The preparation process of crystal form of the present invention
In, it is filtered into conventional solid-liquid separate mode known in the art.
Embodiment 1
With dioxane by dextrorotation Oxiracetam with concentration 18mg/mL dissolution, seal, temperature be 25 DEG C with
The speed of 200r/min stirs 23h, and filtrate is stood volatilization crystallization, collects crystal by filtering, in temperature is 65 by the crystallization of collection
DEG C, relative humidity dry 6h under conditions of being 20% obtains colourless sand shaped crystal.By obtained dextrorotation Oxiracetam crystal into
Row powder diffraction experiment: room temperature test, test-strips test equipment condition: are carried out using Bruker D2 PHASER powder diffractometer
Part are as follows: with Cu KaFor light source, voltage 30kV, electric current 10mA test 0.014 ° of step-length, scanning speed 0.1s/
Step, 5-40 ° of scanning range (2 θ).Through detecting, dextrorotation Oxiracetam crystal prepared by embodiment 1 is in 2 θ of angle of diffraction
16.66±0.2°、17.54±0.2°、19.42±0.2°、21±0.2°、22.16±0.2°、23.46±0.2°、25.36±
There is diffraction maximum at 0.2 °, 26.08 ± 0.2 °, 30.96 ± 0.2 °.
Embodiment 2
With dioxane by dextrorotation Oxiracetam with concentration 10mg/mL dissolution, seal, temperature be 20 DEG C with
The speed of 150r/min stirs 20h, and filtrate is stood volatilization crystallization, collects crystal by filtering, in temperature is 50 by the crystallization of collection
DEG C, relative humidity dry 4h under conditions of being 10% obtains colourless sand shaped crystal.It is identified with the method for embodiment 1, embodiment
The crystal of 2 preparations is the phase isomorphism with crystal form prepared by embodiment 1.
Embodiment 3
With dioxane by dextrorotation Oxiracetam with concentration 40mg/mL heating for dissolving, seal, temperature be 30 DEG C with
The speed of 300r/min stirs 25h, and filtrate is stood volatilization crystallization, collects crystal by filtering, in temperature is 75 by the crystallization of collection
DEG C, relative humidity dry 7h under conditions of being 30% obtains colourless sand shaped crystal.It is identified with the method for embodiment 1, embodiment
The crystal of 3 preparations is the phase isomorphism with crystal form prepared by embodiment 1.
Embodiment 4
Prescription: it forms sediment referring to the dextrorotation Oxiracetam 70g, lactose 12g, carboxymethyl of the crystal form of 1 method of embodiment preparation
Powder sodium 6g, low-substituted hydroxypropyl cellulose 3g, superfine silica gel powder 2g, cellulose acetate benzenetricarboxylic acid ester 7g.
Using following steps: by crystal form dextrorotation Oxiracetam, lactose, sodium carboxymethyl starch and low-substituted hydroxypropyl fiber
Element sieving, is added in dry granulating machine and pelletizes, control the hydraulic system pressure 11MPa of dry granulating machine, and host speed regulation≤
20Hz, straight feeding frequency 8Hz, vertical feeding frequency 12Hz crushed 60 meshes；By gained particle in 65 DEG C of dry 50min
After be cooled to 20 DEG C dextrorotation Oxiracetam particle be made with bottom discharge, lubricant is added, is put into rotary tabletting after mixing
Label is made in tabletting in machine；Turntable revolving speed 30r/min, stuffing pressure 30N, depth of fill 15mm；Then label is placed in
In coating pan, preheating started to spray the enteric-coating material ethanol solution that concentration is 78% into coating pan after 18 minutes, blew simultaneously
Hot wind, the revolving speed 12rpm of coating pan, inlet air temperature be 35 DEG C, when increase weight 9% when, stop coating, be dried to obtain dextrorotation of the present invention
Oxiracetam enteric coatel tablets.
Embodiment 5
Prescription: it forms sediment referring to the dextrorotation Oxiracetam 60g, lactose 20g, carboxymethyl of the crystal form of 2 method of embodiment preparation
Powder sodium 5g, low-substituted hydroxypropyl cellulose 5g, superfine silica gel powder 1g, acetate fiber phthalate ester 9g.
Using following steps: by crystal form dextrorotation Oxiracetam, lactose, sodium carboxymethyl starch and low-substituted hydroxypropyl fiber
Element sieving, is added in dry granulating machine and pelletizes, control the hydraulic system pressure 8MPa of dry granulating machine, and host speed regulation≤
18Hz, straight feeding frequency 7Hz, vertical feeding frequency 7Hz crushed 60 meshes；By gained particle after 50 DEG C of dry 60min
It is cooled to 20 DEG C and dextrorotation Oxiracetam particle is made with bottom discharge, lubricant is added, is put into rotary tablet machine after mixing
Label is made in middle tabletting；Turntable revolving speed 30r/min, stuffing pressure 30N, depth of fill 15mm；
Then label is placed in coating pan, preheating started to spray the enteric packet that concentration is 75% into coating pan after 15 minutes
Clothing material ethanol solution, while blowing hot-air, the revolving speed 10rpm of coating pan, inlet air temperature be 30 DEG C, when increase weight 8% when, stop packet
Clothing is dried to obtain dextrorotation Oxiracetam enteric coatel tablets of the present invention.
Embodiment 6
Prescription: referring to dextrorotation Oxiracetam 75g, the sucrose 5g, carboxymethyl starch of the crystal form of 3 method of embodiment preparation
Sodium 8g, hypromellose 5g, magnesium stearate 1g, methacrylic acid copolymer 6g.
Using following steps: by crystal form dextrorotation Oxiracetam, sucrose, sodium carboxymethyl starch and low-substituted hydroxypropyl fiber
Element sieving, is added in dry granulating machine and pelletizes, control the hydraulic system pressure 15MPa of dry granulating machine, and host speed regulation≤
22Hz, straight feeding frequency 12Hz, vertical feeding frequency 15Hz crushed 60 meshes；By gained particle in 75 DEG C of dry 30min
After be cooled to 20 DEG C dextrorotation Oxiracetam particle be made with bottom discharge, lubricant is added, is put into rotary tabletting after mixing
Label is made in tabletting in machine；Turntable revolving speed 30r/min, stuffing pressure 30N, depth of fill 15mm；Then label is placed in
In coating pan, preheating started to spray the enteric-coating material ethanol solution that concentration is 85% into coating pan after 30 minutes, blew simultaneously
Hot wind, the revolving speed 15rpm of coating pan, inlet air temperature are 40 DEG C, when increase weight 12% when, stop coating, be dried to obtain the right side of the invention
Revolve Oxiracetam enteric coatel tablets.
Embodiment 7
The molten of dextrorotation Oxiracetam enteric coatel tablets of the present invention is investigated referring to the relevant regulations of Chinese Pharmacopoeia version in 2015
Out-degree.The judgment criteria of dissolution rate in stomach are as follows: according to the second method (slurry in " dissolution rate and the drug release determination method " of 2015 editions pharmacopeia
Method) it is used as guidance method, simulated gastric fluid physiological condition is simulated, experimental design is carried out, finally by visually observing.Specifically: amount
0.1mol/L hydrochloric acid solution 900ml is taken, is injected in stripping rotor, heating makes solution temperature be kept for 37 ± 0.5 DEG C, and quantitative precision weighs
6, dextrorotation Oxiracetam enteric coatel tablets sample obtained by 5-7 of the embodiment of the present invention, investment turn in basket, and machine is with revolving speed
100rpm operating, samples respectively at 10min, 30min, 60min, 90min, 120min, through 0.8um micropore water phase filter membrane mistake
Filter is completed in 30s from sampling to filtration, and sample measures absorbance at 276nm wavelength, and using coordinative solvent as blank pair
According to by external standard method calculating dextrorotation Oxiracetam dissolution percentage.
The judgment criteria of dissolution rate in intestines are as follows: according to the second method in " dissolution rate and the drug release determination method " of 2015 editions pharmacopeia
(slurry processes) are used as guidance method, simulate simulated intestinal fluid physiological condition, experimental design are carried out, finally by visually observing.Specifically:
Phosphate buffer (pH=6.8) 900ml is measured, is injected in stripping rotor, heating makes solution temperature be kept for 37 ± 0.5 DEG C, quantitative essence
Close to weigh dextrorotation Oxiracetam enteric coatel tablets sample obtained by 5-7 of the embodiment of the present invention, each embodiment sample takes 6, investment
Turn in basket, machine and remain in operation, samples in 10min, 30min, 60min, 120min, 180min, 240min, pass through immediately
0.8um micropore water phase membrane filtration is completed in 30s from sampling to filtration, and sample measures absorbance at 276nm wavelength, and
Using coordinative solvent as blank control, dextrorotation Oxiracetam is calculated by external standard method and dissolves out percentage.
As the result is shown: the dextrorotation Oxiracetam enteric coatel tablets of 5-7 of embodiment of the present invention preparation dissolve out less, master in gastric juice
It to be dissolved out in intestinal juice, dissolution rate is greater than 90%, illustrates that dextrorotation Oxiracetam enteric coatel tablets prepared by the present invention are quality controllable, energy
Guarantee the safe and effective of clinical use.
Embodiment 8
According to the stability testing method of Chinese Pharmacopoeia two annex of version in 2015, to dextrorotation obtained by embodiment 5-7
Oxiracetam enteric coatel tablets carry out accelerated test and long-term stable experiment respectively, accelerated test in temperature 60 C ± 2 DEG C, it is relatively wet
Degree is investigated 6 months under the conditions of being 35% ± 5%, and long term test is examined under the conditions of 25 ± 2 DEG C of temperature, relative humidity are 30 ± 5%
It examines 24 months, as a result as can be seen that investigating 6 by the dextrorotation Oxiracetam enteric coatel tablets accelerated test of the present invention of embodiment 5-7 preparation
A month, long term test was investigated 24 months, and Key Quality Indicator character, dissolution rate, related substance, content have no significant change, non-
Often stablize, shows that dextrorotation Oxiracetam enteric coatel tablets of the present invention are stable and controllable for quality, clinical use is safer and more effective.
Claims (8)
1. a kind of dextrorotation Oxiracetam enteric coatel tablets, it is characterised in that: include 55~80% in the dextrorotation Oxiracetam enteric coatel tablets
Crystal form dextrorotation Oxiracetam, 5~25% fillers, 5-10% sodium carboxymethyl starch, 3-10% low-substituted hydroxypropyl cellulose,
1-5% lubricant, the enteric material of 5-12%, by percentage to the quality；The dextrorotation Oxiracetam of the crystal form uses
Cu-K α radiation, obtained X- ray powder diffraction are composed in 2 θ of angle of reflectionFor16.66±0.2°、17.54±0.2°、19.42±
Have at 0.2 °, 21 ± 0.2 °, 22.16 ± 0.2 °, 23.46 ± 0.2 °, 25.36 ± 0.2 °, 26.08 ± 0.2 °, 30.96 ± 0.2 °
Diffraction maximum；The filler is selected from microcrystalline cellulose, lactose, mannitol, sorbierite, amylum pregelatinisatum, dextrin, sucrose, anhydrous
At least one of calcium monohydrogen phosphate；The lubricant be selected from magnesium stearate, calcium stearate, zinc stearate, polyethylene glycol, talcum powder and
At least one of superfine silica gel powder；The enteric-coating material is selected from acetate fiber phthalate ester, methacrylic acid copolymer, acetic acid
At least one of cellulose benzenetricarboxylic acid ester and hydroxypropyl cellulose phthalate ester.
2. dextrorotation Oxiracetam enteric coatel tablets as described in claim 1, it is characterised in that: wrapped in the dextrorotation Oxiracetam enteric coatel tablets
Containing 60~75% crystal form dextrorotation Oxiracetam, 5~20% fillers, 5-10% sodium carboxymethyl starch, the low substitution hydroxyl of 3-10%
Third cellulose, 1-3% lubricant, the enteric material of 5-10%, by percentage to the quality.
3. dextrorotation Oxiracetam enteric coatel tablets as claimed in claim 2, it is characterised in that: the filler be selected from microcrystalline cellulose,
Lactose, mannitol, sorbierite, sucrose are at least one.
4. the dextrorotation Oxiracetam enteric coatel tablets as described in claim any one of 1-3, it is characterised in that: the sodium carboxymethyl starch with
The mass ratio of low-substituted hydroxypropyl cellulose is 1~2:1.
5. dextrorotation Oxiracetam enteric coatel tablets as claimed in claim 4, it is characterised in that: wrapped in the dextrorotation Oxiracetam enteric coatel tablets
Containing 60~75% crystal form dextrorotation Oxiracetam, 5~20% lactose, 5-10% sodium carboxymethyl starch, 3-10% low-substituted hydroxypropyl
Cellulose, 1-3% superfine silica gel powder, the cellulose acetate benzenetricarboxylic acid ester of 5-10%, by percentage to the quality；The carboxymethyl starch
The mass ratio of sodium and low-substituted hydroxypropyl cellulose is 1~2:1.
6. the dextrorotation Oxiracetam enteric coatel tablets as described in claim any one of 1-5, it is characterised in that: the right side of the crystal form
Rotation Oxiracetam is made with the following method: dextrorotation Oxiracetam dissolved with concentration 10mg/mL-40mg/mL with dioxane,
It seals, is that the 20-30 DEG C of speed with 150-300r/min stirs 20-25h in temperature, filtrate is stood volatilization knot by filtering
Crystalline substance collects crystal, is 50-75 DEG C in temperature, relative humidity dry 4-7h under conditions of being 15-30%, both.
7. the preparation method of dextrorotation Oxiracetam enteric coatel tablets, is made by dry granulation tabletting as described in claim any one of 1-6
Label, then enteric coatel tablets are made in label enteric coating, which is characterized in that the label is made by following steps: by crystal form
Dextrorotation Oxiracetam and other auxiliary materials are sieved, and are added in dry granulating machine and pelletize, control the hydraulic system of dry granulating machine
8~15MPa of pressure, host speed regulation≤22Hz, 7~12Hz of straight feeding frequency, 7~15Hz of vertical feeding frequency crushed 60
Mesh；Gained particle is cooled to 20 DEG C after 50-75 DEG C of dry 30~60min, dextrorotation Oxiracetam is made with bottom discharge
Then grain is added lubricant and mixes, label is made in tabletting.
8. the preparation method of dextrorotation Oxiracetam enteric coatel tablets as claimed in claim 7, which comprises the steps of: (1)
It prepares crystal form dextrorotation Oxiracetam: being added dextrorotation Oxiracetam with concentration 10mg/mL-40mg/mL dissolution with dioxane
Lid sealing is that the 20-30 DEG C of speed with 150-300r/min stirs 20-25h in temperature, and filtrate is stood volatilization crystallization by filtering,
Crystal is collected, is 50-75 DEG C in temperature, it is difficult to understand both to have obtained crystal form dextrorotation by relative humidity dry 4-7h under conditions of being 15-30%
La Xitan；(2) dry granulation prepares label: crystal form dextrorotation Oxiracetam and other auxiliary materials being sieved, dry granulation is added
It pelletizes in machine, controls 8~15MPa of hydraulic system pressure of dry granulating machine, host speed regulation≤22Hz, straight feeding frequency
7~12Hz, 7~15Hz of vertical feeding frequency, crushed 60 meshes；Gained particle is dropped after 50-75 DEG C of dry 30~60min
Dextrorotation Oxiracetam particle is made to 20 DEG C with bottom discharge in temperature, and lubricant is then added and mixes, label is made in tabletting；(3) enteric
Coating: and then label is placed in coating pan, preheating started to spray the intestines that concentration is 75~85% into coating pan after 15~30 minutes
Molten coating material ethanol solution, while blowing hot-air, the revolving speed 10-15rpm of coating pan, inlet air temperature is 30~40 DEG C, when weight gain 8
When~12%, stops coating, be dried to obtain dextrorotation Oxiracetam enteric coatel tablets.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| CN201810371483 | 2018-04-24 | ||
| CN2018103714834 | 2018-04-24 |
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| CN110393707A true CN110393707A (en) | 2019-11-01 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766596A (en) * | 2009-01-04 | 2010-07-07 | 北京润德康医药技术有限公司 | Solid preparation with dextro-oxiracetam as active component |
| CN102603607A (en) * | 2011-01-21 | 2012-07-25 | 重庆润泽医疗器械有限公司 | Preparation method of (R)-oxiracetam |
-
2018
- 2018-08-22 CN CN201810960824.1A patent/CN110393707A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766596A (en) * | 2009-01-04 | 2010-07-07 | 北京润德康医药技术有限公司 | Solid preparation with dextro-oxiracetam as active component |
| CN102603607A (en) * | 2011-01-21 | 2012-07-25 | 重庆润泽医疗器械有限公司 | Preparation method of (R)-oxiracetam |
Non-Patent Citations (1)
| Title |
|---|
| 袁利杰等: "HPLC 法测定奥拉西坦原料及其注射剂中奥拉西坦的含量和有关物质", 《中国药师》 * |
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