CN108451916A - A kind of paracetamol drug combination preparation and preparation method thereof - Google Patents
A kind of paracetamol drug combination preparation and preparation method thereof Download PDFInfo
- Publication number
- CN108451916A CN108451916A CN201810632323.0A CN201810632323A CN108451916A CN 108451916 A CN108451916 A CN 108451916A CN 201810632323 A CN201810632323 A CN 201810632323A CN 108451916 A CN108451916 A CN 108451916A
- Authority
- CN
- China
- Prior art keywords
- preparation
- gradient
- paracetamol
- temperature
- mesh
- 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.)
- Granted
Links
Classifications
-
- 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
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K9/2009—Inorganic 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
- A61K9/20—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
- A61K9/2095—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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of paracetamol drug combination preparations and preparation method thereof, and preparation method includes the following steps：Paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, Nipasol are added into binder aqueous solution after mixing, pelletized；It is dried using the method for gradient alternating temperature after granulation, the temperature of each gradient controls between 20 40 DEG C, and alginic acid, calcium carbonate, colloidal silicon dioxide are added after dry and premixes 3 5min, then adds magnesium stearate and mixes 3 5min, tabletting, coating.The preparation method of the paracetamol drug combination preparation of the embodiment of the present invention, operating procedure itself is simple, and operating condition is mild, and the Fast Stripping of the active ingredient in said preparation may be implemented by the preparation method, dissolution rate is improved, should be widely promoted and applied.
Description
Technical field
The present invention relates to pharmaceutical fields, in particular to a kind of paracetamol drug combination preparation and its system
Preparation Method.
Background technology
Paracetamol is the antipyretic-antalgic anti-inflammatory agent of phenyl amines, and antipyretic effect is stronger and lasting, and indication is
For generating heat caused by common cold or influenza, it is also used for alleviating mild to moderate pain such as headache, arthralgia, inclined head
Bitterly, toothache, courbature, neuralgia, dysmenorrhoea, manufactured finished product take orally 0.3-0.6g or so, and children press 10- of weight
15mg/kg, every 4-6 hours 1 time；Children are no more than 5 dosage for every 24 hours within 12 years old or less, and the course for the treatment of is no more than 5 days.And the product
It should not take for a long time.
In the prior art, the preparation method of general Aceta Elixir is to use the common mixing granulation of supplementary material
The particle of mode, preparation can be collapsed through the mixed total mixture of supplementary material in placement or tableting processes because of crospovidone water suction
Solution, keeps the surface of tablet scared, influences appearance, and also results in that drug effect is unstable, the qualification rate of production is reduced, for not conforming to
The product of lattice must reworked processing, lead to low production efficiency, and do not meet GMP administrative provisions, this method is prepared in addition
Preparation is bigger to stomach stimulation, be easy to cause the damage to gastrointestinal tract, is also easy to cause patient's others adverse reaction.
In view of this, special propose the present invention.
Invention content
The first object of the present invention is to provide a kind of preparation method of paracetamol drug combination preparation, entirely
The auxiliary material of preparation process is in the outer adduction plus by the way of being combined, crospovidone, PVP K30, methyl hydroxybenzoate, oxybenzene second
Plus, calcium carbonate and alginic acid select additional mode, outside in these auxiliary materials of ester, Nipasol and paracetamol major ingredient are common
Add auxiliary material that can play the role of closing water conservation, the addition of magnesium stearate can be in order to tabletting, realization tablet fater disintegration, in addition
Calcium carbonate can be made to spread rapidly by additional mode to improve the pH value of gastric juice, alginic acid rapidly diffuses into gastric mucosa shape
At protective layer, stomach is protected to form dual fail-safe, damage of the Paracetamol to gastrointestinal tract is avoided, reduces adverse reaction, it should
Preparation method is scientific and reasonable, to significantly improve the bioavilability of Aceta Elixir, is utilized suitable for being widely popularized,
Limited fewer, processing step is easy to operate.
The second object of the present invention is to provide what a kind of preparation method of above-mentioned Aceta Elixir was prepared
Paracetamol drug combination preparation, the Aceta Elixir quality is uniform, and physicochemical properties are stablized, drug effect ratio
It is more significant.
In order to realize that the above-mentioned purpose of the present invention, spy use following technical scheme：
The present invention provides a kind of preparation methods of paracetamol drug combination preparation, specifically include following step
Suddenly：
(A) paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, Nipasol are mixed
Binder aqueous solution is added after uniformly, is pelletized；
(B) mixing speed pelletized is between 200-400rpm, Granulation time 90-180s；
(C) method of gradient alternating temperature is used to be dried, the temperature of each gradient controls between 20-40 DEG C, and previous
Gradient is in back and forth alternate trend with the temperature of latter gradient, and 4-5 DEG C is differed between adjacent two gradients, sea is added after dry
Alginic acid, calcium carbonate, colloidal silicon dioxide premix 3-5min, then add magnesium stearate mixing 3-5min, tabletting, coating.
General is to be prepared in such a way that main and supplementary materials add together, but auxiliary material adds not together in the prior art
Conducive to the quality of guarantee tablet, for example the crospovidone added just is easy to keep slice, thin piece surface scared due to disintegration because absorbing water, shadow
Ring appearance.And in the course of time, it also results in that drug effect is unstable, reduces the qualification rate of production, it must for underproof product
Reworked processing leads to low production efficiency, and does not meet GMP administrative provisions, and the preparation that this method is prepared in addition pierces stomach
It is sharp bigger, it is be easy to cause the damage to gastrointestinal tract, is also easy to cause patient's others adverse reaction.
In order to solve the above technical problems, The present invention provides a kind of preparations of paracetamol drug combination preparation
Method forms package blocking effect by using the mode for meeting addition inside and outside auxiliary material, and the first benefit of the blocking effect ensures
Total mixture is not easy dehydration and the moisture absorption, stablizes within the scope of 2-3%, to ensure tabletting not sliver, ensures long term storage, stability
It is high.Second benefit is that product long-term storage is not easy the moisture absorption, prevents crospovidone because the moisture absorption generates disintegration, unilateral scared, is influenced
Presentation quality.Third benefit is calcium carbonate and the additional stimulation for solving paracetamol to gastric mucosa of alginic acid, is reduced bad
Reaction.Its principle：Both substances are discharged with powdered addition hybrid particles prior to composition in particle, in calcium carbonate and hydrochloric acid in gastric juice,
Stomach inner pH value can be promoted rapidly, and alginic acid can uniformly diffuse to form gastric mucosal protection layer, and duplicate protection reduces paracetamol
Stimulation to gastrointestinal tract.The preparation that method using the present invention is prepared will be than in the prior art common paracetamol
Preparation is relatively beneficial to health to gastrointestinal irritability smaller.
Preferably, the mesh granularity of the paracetamol controls more than 80 mesh.
Preferably, the mesh granularity of the crospovidone controls more than 80 mesh.
Preferably, the mesh granularity of the PVP K30 controls more than 80 mesh.
Preferably, described adhesive aqueous solution is pregelatinized starch aqueous solution.
Preferably, the mass percent concentration of the pregelatinized starch aqueous solution is 15wt% or more.
Preferably, in the step (C), the section of gradient alternating temperature is three, and the temperature of first gradient is controlled in 25-30
DEG C, at 35-40 DEG C, the temperature of 3rd gradient is controlled at 25-30 DEG C for the temperature control of the second gradient；
Preferably, the dry time is 30-40min.
Preferably, in the step (C), hardness control is between 80-140N in tableting processes；
Preferably, the plain piece that hardness is 80-140N is coated, waits for that hardness rises between 180-200N, stop packet
Clothing.
Compared with prior art, beneficial effects of the present invention are：
(1) auxiliary material of the present invention is in the outer adduction plus by the way of being combined, crospovidone, PVP K30, oxybenzene first
Plus, calcium carbonate and alginic acid selection are additional in these auxiliary materials of ester, ethyl hydroxy benzoate, Nipasol and paracetamol major ingredient are common
Mode, additional auxiliary material can play the role of closing water conservation, the addition of magnesium stearate can in order to tabletting, realize that tablet is quick
Disintegration；
(2) present invention can make calcium carbonate is spread rapidly to neutralize hydrochloric acid in gastric juice by additional mode, to improve the pH of gastric juice
Value, alginic acid rapidly diffuse into gastric mucosa and form protective layer, protect stomach to form dual fail-safe, avoid Paracetamol to stomach
The stimulation of enteron aisle damages, and reduces adverse reaction；
(3) preparation method provided by the present invention, front and back step linking is close, is easy to form industrialization, the system prepared
Agent therapeutic effect is notable；
(4) paracetamol drug combination preparation quality provided by the invention is uniform, and physicochemical properties are stablized, medicine
Effect is than more significant.
Specific implementation mode
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer is
The conventional products that can be obtained by commercially available purchase.
According to an aspect of the present invention, a kind of preparation method of paracetamol drug combination preparation includes as follows
Step：
(A) paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, Nipasol are mixed
Binder aqueous solution is added after uniformly, is pelletized；
(B) mixing speed pelletized is between 200-400rpm, Granulation time 90-180s；
(C) method of gradient alternating temperature is used to be dried, the temperature of each gradient controls between 20-40 DEG C, and previous
Gradient is in back and forth alternate trend with the temperature of latter gradient, and 4-5 DEG C is differed between adjacent two gradients, sea is added after dry
Alginic acid, calcium carbonate, colloidal silicon dioxide premix 3-5min, then add magnesium stearate mixing 3-5min, tabletting, coating.
The present invention provides a kind of preparation methods of paracetamol drug combination preparation, inside and outside auxiliary material
The mode for meeting addition forms package blocking effect, and the first benefit of the blocking effect ensures that total mixture is not easy dehydration and the moisture absorption,
Stablize within the scope of 2-3%, to ensure tabletting not sliver, ensures that long term storage, stability are high.Second benefit is that product is long-term
Storage is not easy the moisture absorption, prevents crospovidone because the moisture absorption generates disintegration, unilateral scared, influences presentation quality.Third benefit is carbon
Sour calcium and the additional stimulation for solving paracetamol to gastric mucosa of alginic acid, reduce adverse reaction.Its principle：Both substances
It with powdered addition hybrid particles, is discharged prior to composition in particle, calcium carbonate can neutralize rapidly hydrochloric acid in gastric juice, promote stomach inner pH value, sea
Alginic acid can uniformly diffuse to form gastric mucosal protection layer, and duplicate protection reduces stimulation of the paracetamol to gastrointestinal tract.Using this
The preparation that the method for invention is prepared will be than in the prior art common Aceta Elixir to gastrointestinal irritability smaller,
It is relatively beneficial to health.
In the preferred embodiment of the present invention, the mesh granularity of the paracetamol controls more than 80 mesh.
In the preferred embodiment of the present invention, the mesh granularity of the crospovidone controls more than 80 mesh.
In the preferred embodiment of the present invention, the mesh granularity of the PVP K30 controls more than 80 mesh.
After being defined the granular size of each raw material, the degree of merging into each other between raw material can be improved, is made
The preparation quality that must be prepared is more uniform.
In the preferred embodiment of the present invention, described adhesive aqueous solution is pregelatinized starch aqueous solution.
In the preferred embodiment of the present invention, the mass percent concentration of the pregelatinized starch aqueous solution is
15wt% or more.If the excessive performance for being unfavorable for effective component of the concentration of adhesive, therefore concentration should not be too high.
In the preferred embodiment of the present invention, in the step (C), the section of gradient alternating temperature is three, first
The temperature control of gradient is at 25-30 DEG C, and at 35-40 DEG C, the temperature of 3rd gradient is controlled in 25-30 for the temperature control of the second gradient
℃；
In the preferred embodiment of the present invention, the dry time is 30-40min.
It should be noted that by the way of the Cryogenic Temperature Swing that the entire drying process of the present invention uses is dried, temperature range is back and forth
The mode of checker, the more conducively broken wall of drug molecule, the performance of active ingredient, therefore the advantage of alternating temperature drying are apparent excellent
In the mode of freeze-day with constant temperature.
In the preferred embodiment of the present invention, in the step (C), hardness control is in 80- in tableting processes
Between 140N；
In the preferred embodiment of the present invention, the plain piece that hardness is 80-140N is coated, waits for that hardness rises
To between 180-200N, stop coating.
When specifically being operated, hardness is the tablet of 80-140N, starts to be coated after preheating dry plate in coating pan, coated
Afterwards, when hardness is risen to naturally between 180-200N, can stop being coated.
The solution of the present invention is further detailed with reference to embodiment and comparative example.
Embodiment 1
1) according to production requirement, paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, hydroxyl
These materials of phenylpropyl alcohol ester, alginic acid, calcium carbonate, colloidal silicon dioxide, magnesium stearate are weighed, the mesh granularity of above-mentioned supplementary material
Control is more than 80 mesh；
2) adhesive is prepared：The pregelatinized starch for weighing the adhesive of half recipe quantity preparation adds proper amount of boiling water dispersion molten
Solution, after being cooled to room temperature, obtains pregelatinized starch aqueous solution；
3) mixing granulation：By paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, oxybenzene
After being mixed evenly in propyl ester input wet granulator, pregelatinized starch aqueous solution is added, opens stirring, shearing, stirring speed
Rate is 200rpm, and Granulation time controls within 90s；
4) whole wet granulars are set in fluid bed, carry out alternating temperature drying process, alternating temperature dry section be three sections, first
The temperature setting of gradient is at 35 DEG C, and the temperature setting of the second gradient is at 40 DEG C, and the temperature setting of 3rd gradient is at 35 DEG C, and drying is extremely
After moisture 2wt%-3wt%, you can shut down discharging, total drying time is 30min；
5) piece weight is calculated according to particle drug content, alginic acid, calcium carbonate, colloidal silica is added in the batch mixing after drying
Silicon premixes 3min, then adds magnesium stearate mixing 5min and be put into tablet press machine, tablet press machine rotating speed 30-40rpm, hardness：80-
140N first adjusts loading manually, rear to adjust pressure alternately, checks the indexs such as tablet weight variation, character, is opened after qualified
Beginning tabletting, 20min checks primary piece weight, average piece weight and weight differential in tableting processes, and performs record；
6) start to be coated after tabletting, 45-50 DEG C of inlet air temperature of setting, preheating 1 hour, adjusting coating drum rotating speed is
3rpm adjusts wriggling revolution speed and is equably sprayed on syrup in plain piece, and hardness rises to 180-200N, i.e. coating weight gain naturally
When 2.0%-3.0%, heating is closed, continues air inlet cooling, stops coating operations；
7) Aceta Elixir made is packed, posts label, hermetically drying preserves.
Embodiment 2
1) according to production requirement, paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, hydroxyl
These materials of phenylpropyl alcohol ester, alginic acid, calcium carbonate, colloidal silicon dioxide, magnesium stearate are weighed, the mesh granularity of above-mentioned supplementary material
Control is more than 90 mesh；
2) adhesive is prepared：The pregelatinized starch for weighing the adhesive of half recipe quantity preparation adds proper amount of boiling water dispersion molten
Solution after being cooled to room temperature, obtains the pregelatinized starch aqueous solution that mass percent concentration is 15wt%；
3) mixing granulation：By paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, oxybenzene
After being mixed evenly in propyl ester input wet granulator, pregelatinized starch aqueous solution is added, opens stirring, shearing, stirring speed
Rate is 400pm, and Granulation time controls within 180s；
4) whole wet granulars are set in fluid bed, carry out alternating temperature drying process, alternating temperature dry section be three sections, first
The temperature setting of gradient is at 25 DEG C, and the temperature setting of the second gradient is at 30 DEG C, and the temperature setting of 3rd gradient is at 25 DEG C, and drying is extremely
After moisture 2wt%-3wt%, you can shut down discharging, total drying time is 40min；
5) piece weight is calculated according to particle drug content, alginic acid, calcium carbonate, colloidal silica is added in the batch mixing after drying
Silicon premixes 4min, then adds magnesium stearate mixing 4min and be put into tablet press machine, tablet press machine rotating speed 30-40rpm, hardness：80-
140N first adjusts loading manually, rear to adjust pressure alternately, checks the indexs such as tablet weight variation, character, is opened after qualified
Beginning tabletting, 20min checks primary piece weight, average piece weight and weight differential in tableting processes, and performs record；
6) start to be coated after tabletting, 45-50 DEG C of inlet air temperature of setting, preheating 1 hour, adjusting coating drum rotating speed is
3rpm adjusts wriggling revolution speed and is equably sprayed on syrup in plain piece, and hardness rises to 180-200N, i.e. coating weight gain naturally
When 2.0%-3.0%, heating is closed, continues air inlet cooling, stops coating operations；
7) Aceta Elixir made is packed, posts label, hermetically drying preserves.
Embodiment 3
1) according to production requirement, paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, hydroxyl
These materials of phenylpropyl alcohol ester, alginic acid, calcium carbonate, colloidal silicon dioxide, magnesium stearate are weighed, the mesh granularity of above-mentioned supplementary material
Control is more than 90 mesh；
2) adhesive is prepared：The pregelatinized starch for weighing the adhesive of half recipe quantity preparation adds proper amount of boiling water dispersion molten
Solution after being cooled to room temperature, obtains the pregelatinized starch aqueous solution that mass percent concentration is 15wt%；
3) mixing granulation：By paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, oxybenzene
After being mixed evenly in propyl ester input wet granulator, pregelatinized starch aqueous solution is added, opens stirring, shearing, stirring speed
Rate is 300pm, and Granulation time controls within 100s；
4) whole wet granulars are set in fluid bed, carry out alternating temperature drying process, alternating temperature dry section be three sections, first
The temperature setting of gradient is at 25 DEG C, and the temperature setting of the second gradient is at 30 DEG C, and the temperature setting of 3rd gradient is at 25 DEG C, and drying is extremely
After moisture 2wt%-3wt%, you can shut down discharging, total drying time is 35min；
5) piece weight is calculated according to particle drug content, alginic acid, calcium carbonate, colloidal silica is added in the batch mixing after drying
Silicon premixes 4min, then adds magnesium stearate mixing 4min and be put into tablet press machine, tablet press machine rotating speed 30-40rpm, hardness：80-
140N first adjusts loading manually, rear to adjust pressure alternately, checks the indexs such as tablet weight variation, character, is opened after qualified
Beginning tabletting, 20min checks primary piece weight, average piece weight and weight differential in tableting processes, and performs record；
6) start to be coated after tabletting, set 45-50 DEG C of inlet air temperature, preheating 1 hour adjust coating drum rotating speed as 3rpm,
It adjusts wriggling revolution speed to be equably sprayed on syrup in plain piece, hardness rises to 180-200N, i.e. coating weight gain naturally
When 2.0%-3.0%, heating is closed, continues air inlet cooling, stops coating operations；
7) Aceta Elixir made is packed, posts label, hermetically drying preserves.
Comparative example 1
Concrete operation step is consistent with embodiment 3, and temperature is controlled at 20-30 DEG C in fluidized drying pelletizer in step 4)
Between, not by the way of alternating temperature drying.
Comparative example 2
Concrete operation step is consistent with embodiment 3, and only in step 4), it is three sections, the first ladder that alternating temperature, which dries section,
The temperature setting of degree is at 40 DEG C, and the temperature setting of the second gradient is at 50 DEG C, and the temperature setting of 3rd gradient is at 40 DEG C.
Comparative example 3
Concrete operation step and embodiment 3 are consistent, only alginic acid, calcium carbonate, colloidal silicon dioxide granulation process
Middle addition.
Experimental example 1
Kunming mouse is randomly divided into：Blank control group, embodiment 1-3 be respectively one group of sample, two groups of sample with
And three groups of sample, comparative example 1-3 are respectively six groups of four groups of sample, five groups of sample and sample, sample group successive administration acetyl ammonia
After the identical dosage 7d of base phenol agents composite preparation, takes gastric tissue to be visually observed and histopathologic examination, as a result show
Show：The gastric tissue naked eyes of one group of sample to three groups of sample are seen and histopathologic examination's mucous membrane is showed no obvious abnormalities, sample four
There is different degrees of mucosal atrophy and oedema in the gastric tissue of group to six groups of sample, and the wherein gastric tissue oedema of six groups of sample shows
As even more serious.
Experimental example 2
Paracetamol drug combination preparation in above-mentioned each embodiment and comparative example is used《Chinese Pharmacopoeia》
The two paracetamol tablets quality standard dissolution methods of version in 2015 are tested, and wherein concrete outcome see the table below 1.
Table 1 dissolves out data result
It can be seen that the paracetamol drug combination preparation dissolution of the embodiment of the present invention from the data in above-mentioned table
Excellent effect, compared to the preparation method of comparative example, drug effect can more significantly.
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that without departing substantially from the present invention's
Many other change and modification can be made in the case of spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (10)
1. a kind of preparation method of paracetamol drug combination preparation, which is characterized in that include the following steps：
(A) paracetamol, crospovidone, PVP K30, methyl hydroxybenzoate, ethyl hydroxy benzoate, Nipasol are uniformly mixed
After add binder aqueous solution, pelletize；
(B) mixing speed pelletized is between 200-400rpm, Granulation time 90-180s；
(C) method of gradient alternating temperature is used to be dried, the temperature of each gradient controls between 20-40 DEG C, and previous gradient
Temperature with latter gradient is in back and forth alternate trend, and 4-5 DEG C is differed between adjacent two gradients, seaweed is added after dry
Acid, calcium carbonate, colloidal silicon dioxide premix 3-5min, then add magnesium stearate mixing 3-5min, tabletting, coating.
2. preparation method according to claim 1, which is characterized in that the mesh granularity of the paracetamol is controlled 80
It is more than mesh.
3. preparation method according to claim 1, which is characterized in that the mesh granularity of the crospovidone is controlled in 80 mesh
More than.
4. preparation method according to claim 1, which is characterized in that the mesh granularity of the PVP K30 is controlled in 80 mesh
More than.
5. preparation method according to claim 1, which is characterized in that in the step (A), described adhesive aqueous solution is
Pregelatinized starch aqueous solution.
6. preparation method according to claim 5, which is characterized in that the mass percent of the pregelatinized starch aqueous solution
A concentration of 15wt% or more.
7. preparation method according to claim 1, which is characterized in that in the step (C), the section of gradient alternating temperature is three
A, the temperature control of first gradient is at 25-30 DEG C, and at 35-40 DEG C, the temperature of 3rd gradient controls for the temperature control of the second gradient
At 25-30 DEG C；
Preferably, the dry time is 30-40min.
8. preparation method according to claim 7, which is characterized in that in the step (C), hardness controls in tableting processes
Between 80-140N.
9. preparation method according to claim 8, which is characterized in that be 80-140N's to hardness in the step (C)
Plain piece is coated, and waits for that hardness rises between 180-200N, stops coating.
10. the paracetamol drug combination preparation that claim 1-9 any one of them preparation methods are prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810632323.0A CN108451916B (en) | 2018-06-19 | 2018-06-19 | Acetaminophen pharmaceutical composition preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810632323.0A CN108451916B (en) | 2018-06-19 | 2018-06-19 | Acetaminophen pharmaceutical composition preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108451916A true CN108451916A (en) | 2018-08-28 |
| CN108451916B CN108451916B (en) | 2020-08-14 |
Family
ID=63214909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810632323.0A Active CN108451916B (en) | 2018-06-19 | 2018-06-19 | Acetaminophen pharmaceutical composition preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108451916B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110501441A (en) * | 2019-09-27 | 2019-11-26 | 地奥集团成都药业股份有限公司 | Detection method in relation to substance in a kind of paracetamol tablets |
| CN111012750A (en) * | 2019-12-27 | 2020-04-17 | 北京济美堂医药研究有限公司 | Paracetamol tablet and preparation method thereof |
| CN111374953A (en) * | 2018-12-31 | 2020-07-07 | 上海鼎雅药物化学科技有限公司 | Paracetamol tablet and preparation process thereof |
| CN114432256A (en) * | 2021-12-31 | 2022-05-06 | 陕西必康制药集团控股有限公司 | Paracetamol coated tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002100391A1 (en) * | 2001-06-08 | 2002-12-19 | Smithkline Beecham P.L.C. | Swallow tablet comprising paracetamol |
| CN101466359A (en) * | 2006-04-07 | 2009-06-24 | 史密丝克莱恩比彻姆公司 | Fast release paracetamol tablets |
-
2018
- 2018-06-19 CN CN201810632323.0A patent/CN108451916B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002100391A1 (en) * | 2001-06-08 | 2002-12-19 | Smithkline Beecham P.L.C. | Swallow tablet comprising paracetamol |
| CN101466359A (en) * | 2006-04-07 | 2009-06-24 | 史密丝克莱恩比彻姆公司 | Fast release paracetamol tablets |
Non-Patent Citations (1)
| Title |
|---|
| 江菊元等: "变温干燥的实验研究", 《节能》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111374953A (en) * | 2018-12-31 | 2020-07-07 | 上海鼎雅药物化学科技有限公司 | Paracetamol tablet and preparation process thereof |
| CN110501441A (en) * | 2019-09-27 | 2019-11-26 | 地奥集团成都药业股份有限公司 | Detection method in relation to substance in a kind of paracetamol tablets |
| CN110501441B (en) * | 2019-09-27 | 2021-11-26 | 地奥集团成都药业股份有限公司 | Method for detecting related substances in acetaminophen tablet |
| CN111012750A (en) * | 2019-12-27 | 2020-04-17 | 北京济美堂医药研究有限公司 | Paracetamol tablet and preparation method thereof |
| CN114432256A (en) * | 2021-12-31 | 2022-05-06 | 陕西必康制药集团控股有限公司 | Paracetamol coated tablet and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108451916B (en) | 2020-08-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108451916A (en) | A kind of paracetamol drug combination preparation and preparation method thereof | |
| CN102552159B (en) | Rabeprazole sodium enteric-coated micro-pellet and preparation method thereof | |
| WO2018177318A1 (en) | Metformin hydrochloride sustained-release tablets and preparation method therefor | |
| CN105030725B (en) | Vonoprazan fumarate enteric-coated composition and preparation method thereof | |
| CN108042503B (en) | High-efficiency potassium sodium dehydroandroan drographolide succinate enteric-coated tablet and preparation method thereof | |
| CN106176771B (en) | Lamivudine-tenofovir compound tablet and preparation method thereof | |
| CN106265581B (en) | Tranexamic acid tablet and preparation method thereof | |
| CN104000796A (en) | Coating auxiliary materials, preparation method and coating method for Chinese herb extract preparations | |
| CN101747305A (en) | Five crystal forms of nicousamide compound and preparation method, pharmaceutical composition and usage thereof | |
| CN106667936A (en) | Sofosbuvir tablet and preparation method thereof | |
| CN112294770A (en) | Isosorbide mononitrate compound preparation and application and preparation method thereof | |
| CN108420807A (en) | A kind of metformin hydrochloride medicinal composition preparation and preparation method thereof | |
| CN104367588B (en) | Dexamethasone, pectin and zinc combined gel oral colon-specific drug delivery pellet | |
| CN101006991A (en) | Slow release preparation of berberine | |
| CN107519144A (en) | A kind of preparation method of telmisartan amlodipine tablets | |
| CN106589022A (en) | Roxithromycin compound as well as preparation method and pharmaceutical composition thereof | |
| CN104873471A (en) | Rabeprazole sodium tablet and rabeprazole sodium enteric-coated tablet | |
| CN110237097A (en) | A kind of Fufang Anfenwanan capsules pellet and preparation method thereof | |
| CN113332251A (en) | Live bacteria preparation of bacillus coagulans | |
| CN105503764B (en) | Linezolid form B and its production and use | |
| CN111374953A (en) | Paracetamol tablet and preparation process thereof | |
| CN115317459B (en) | Preparation process of chloramphenicol tablets | |
| CN106038523A (en) | Potassium citrate and sodium citrate tablets and preparation method thereof | |
| CN117205200A (en) | Citrus flavone tablet and preparation method thereof | |
| CN102247369B (en) | Compound naproxen esomeprazole medicine composition and preparation method thereof |
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 |