CN109394718A - A kind of amoxicillin dispersible tablet and preparation method thereof - Google Patents
A kind of amoxicillin dispersible tablet and preparation method thereof Download PDFInfo
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Abstract
The present invention relates to a kind of amoxicillin dispersible tablets and preparation method thereof, belong to pharmaceutical technology field.The amoxicillin dispersible tablet, main ingredient Amoxicillin are distributed in slow-released part and immediate release section with weight ratio for the ratio of 4:6；The slow-released part is at least to be made of containing the capsule core that microcrystalline cellulose is packing material the spraying of sustained release coating liquid；The immediate release section is prepared by filler, disintegrating agent and lubricant.Amoxicillin dispersible tablet of the present invention ensure that dissolution release is complete in 4 hours, with the ratio 4:6 of Amoxicillin in time-division slow-released part and quick-release portion, it ensure that dispersible tablet dissolution release is steady and complete, the blood concentration finally realized in vivo is kept long lasting for the level for being higher than MIC, it ensure that the antibacterial effect of Amoxicillin significantly, clinical efficacy significantly improves, while realizing amoxicillin dispersible tablet in the reasonable blood concentration of the good stable state of human body, also ensures the safety of medication.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation and preparation method thereof, in particular to a kind of amoxicillin dispersible tablet and its preparations
Method belongs to pharmaceutical technology field.
Background technique
Amoxicillin (Amoxicillin) is a kind of orally active wide spectrum beta-lactam antibiotic, and mechanism of action is
The synthesis for inhibiting bacteria cell wall, makes its membranolysis, dissolution, and clinic is mainly used for urinary system caused by sensitive bacteria, exhales
The infection of desorption system, biliary tract etc..Amoxicillin dispersible tablet and its conventional tablet ratio, with disintegration time limited is short, drug-eluting is fast, raw
The features such as object availability is high, adverse reaction is few, convenient to take, it has also become the hot spot studied at present, and have launch, clinic is answered
With wide, it has been appended at present as national essential drugs.
There are many report in relation to amoxicillin dispersible tablet in the prior art, as Chinese patent 200810101332.3 discloses
A kind of amoxicillin dispersible tablet is made of Amoxicillin raw medicine and pharmaceutical carrier, and the pharmaceutical carrier includes diluent, collapses
Agent and lubricant are solved, and optionally includes sweetener and/or aromatic；Wherein, the weight of the Amoxicillin raw medicine and pharmaceutical carrier
Amount is than being 3:1；Diluent in the pharmaceutical carrier is micro-crystalline lactose, and disintegrating agent is crosslinked polyvinylpyrrolidone, Yi Jirun
Lubrication prescription is magnesium stearate；For the pharmaceutical carrier with its total weight, three kinds of respective weight percentages of adjuvant are crystallite respectively
Lactose 82%, crosslinked polyvinylpyrrolidone 15% and magnesium stearate 3%；The micro-crystalline lactose be microcrystalline cellulose and
The lactose of spray drying premixes the compound to be formed.The production method uses direct powder compression technology.
Chinese patent 201110289124.2 discloses a kind of amoxicillin dispersible tablet and its production method, it is Ah not
XiLin, microcrystalline cellulose, crospovidone, low-substituted hydroxypropyl cellulose, croscarmellose sodium, magnesium stearate, dioxy
Masterbatch pellet, standby material is respectively prepared by different proportion in SiClx, saccharin sodium, vanillic aldehyde, apricot taste essence, orange taste essence supplementary material
Grain is mixed in a certain ratio again after sub- material particle, by crushing, sieving, magnetic sieve, drying, whole grain, weighing, bond, be pressed into Ah
Amdinocillin dispersible tablet.Increase magnetic riddler sequence in amoxicillin dispersible tablet production method, supplementary material can be crushed, be sieved etc. and processed
Issuable iron powder, thin iron Xiao etc. are sucked out in the process, guarantee the purity of amoxicillin dispersible tablet.
Chinese patent 201410446830.7 discloses a kind of amoxicillin dispersible tablet, preparation method and the usage, is to adopt
Amoxicillin dispersible tablet is prepared with direct powder compression, softwood processed, granulation, drying and other steps is needed not move through, is directly done
Powder tabletting, production process is few, and equipment is simple, and the period is short, avoids influence of the temperature and humidity to product quality, and stability is mentioned
Height, while the disintegration time of the amoxicillin dispersible tablet according to said method prepared is short, dissolution homogeneity is good, to make drug effect
Fastly, it absorbs fastly, its bioavilability can be increased.
Pellet is typical multi-element type drug delivery system developed in recent years, pellet has the advantages that 1. take orally after
Increase with the contact area of gastrointestinal tract mucosa, keeps drug absorption complete, to improve the bioavilability of drug；2. can subtract
Less or drug is eliminated to the irritation etc. of gastrointestinal tract.Extrusion spheronization method is to prepare a kind of common method of large dosage of medicament pellet.
When extrusion spheronization method prepares pellet, microcrystalline cellulose (MCC) is the most commonly used balling-up promotor, gained pellet high income,
Roundness is good.But it has been reported that the disintegration of pellet made from MCC is slow, the dissolution of drug can be delayed.
The present inventor has found during studying amoxicillin dispersible tablet, existing amoxicillin dispersible tablet oral absorption
Fastly, peak time is too early, and half-life period is too short, and the time of the drug of half-life short in vivo is short, that is, duration of efficacy is short,
The fungistatic effect of drug in vivo is seriously affected, it is easier to generate drug resistance.
Summary of the invention
The present invention is studied, and a kind of new amoxicillin dispersible tablet is developed, by the way that Amoxicillin is distributed in sustained release portion
Divide and immediate release section, the dispersible tablet can be such that drug absorption peak reaches steadily, T > MIC time extends, and increases curative effect, reduces secondary work
With.
After amoxicillin dispersible tablet of the present invention administration, a part of Amoxicillin is dissolved out rapidly, blood concentration reach MIC it
On, rapid-onset, subsequent slow-released part slow release maintains vivo medicine concentration to be always held on MIC for a long time, such as
This realize Amoxicillin in vivo for a long time effectively, play better drug effect, solve Amoxicillin in the prior art
Patient's blood concentration is unstable in dispersible tablet use, maintains effective time short, the defect that curative effect is not good enough.
The technical problem to be solved by the present invention is to what is be achieved through the following technical solutions.
A kind of amoxicillin dispersible tablet, ratio of the main ingredient Amoxicillin with weight ratio for 4:6 are distributed in slow-released part and speed
Release part；The slow-released part is at least to be made of containing the capsule core that microcrystalline cellulose is packing material the spraying of sustained release coating liquid；
Slow-release material is processed cashew nut natural gum in the sustained release coating liquid；The immediate release section is by filler, disintegrating agent and lubrication
Agent is prepared；The filler is microcrystalline cellulose, and the disintegrating agent is selected from sodium carboxymethyl starch, cross-linked carboxymethyl cellulose
One or both of receive with crosslinked polyvinylpyrrolidone, the lubricant is selected from magnesium stearate, talcum powder and superfine silica gel powder
One or both of.
Further, above-mentioned amoxicillin dispersible tablet, the capsule core is by main ingredient Amoxicillin and packing material using extrusion
Spheronization is made, wherein packing material also contains one or both of starch and lactose；The sustained release coating liquid is to use 85-
95% ethanol solution dissolves processed cashew nut natural gum, plasticizer, antitackiness agent and is made.Wherein, plasticizer is selected from polyethylene glycol
4000, one or both of triethyl citrate and Ergol, antitackiness agent are selected from magnesium stearate or superfine silica gel powder.
Further, above-mentioned amoxicillin dispersible tablet, microcrystalline cellulose in the capsule core packing material with it is processed
The weight ratio of cashew nut natural gum is 1:1.02-1.08.
Above-mentioned amoxicillin dispersible tablet, the processed cashew nut natural gum, processing method are as follows:
Cashew nut tree rubber pulverizing is crossed into 20 meshes；95% ethyl alcohol, sodium hydroxide and above-mentioned sieving crushed material is by weight 5:
0.5:1 is stirred 5 hours, obtains reaction solution；With in 732 type strong acid ion exchange resins and above-mentioned reaction solution is to pH=7；It filters and removes
Resin, by filtrate decompression distillation and concentration to thick；95% ethyl alcohol is added and stirs, suction filtration muddy to dispersion, filtrate warp is spraying dry
It is dry to obtain processed cashew nut natural gum.
Above-mentioned cashew nut natural gum processing method, the setting condition of the spray drying: 73 DEG C of outlet temperature, inlet temperature 112
DEG C, charging rate 10.5mL/min.
Above-mentioned amoxicillin dispersible tablet, every 1000 are prepared by following supplementary material:
Wherein, slow-released part capsule core dosage need to be converted in the ratio 4:6 of Amoxicillin in slow-released part and immediate release section,
Namely need the capsule core containing 100g main ingredient Amoxicillin.
Above-mentioned amoxicillin dispersible tablet, every 1000 are prepared by following supplementary material:
Wherein, slow-released part capsule core dosage need to be converted in the ratio 4:6 of Amoxicillin in slow-released part and immediate release section,
Namely need the capsule core containing 100g main ingredient Amoxicillin.
Above-mentioned amoxicillin dispersible tablet, every 1000 are prepared by following supplementary material:
Wherein, slow-released part capsule core dosage need to be converted in the ratio 4:6 of Amoxicillin in slow-released part and immediate release section,
Namely need the capsule core containing 100g main ingredient Amoxicillin.
A kind of preparation method of above-mentioned amoxicillin dispersible tablet, includes the following steps:
(1) prepare supplementary material: supplementary material in prescription is sieved with 100 mesh sieve respectively, it is spare；
(2) it prepares capsule core: the main ingredient Amoxicillin of recipe quantity being uniformly mixed with packing material and is placed on wet granulator
In, the purified water for being gradually added into recipe quantity is that softwood is made in wetting agent, and softwood obtained is transferred in extruder, is sieved through squeezing out
Plate is extruded into bar, the bar of extrusion is transferred to round as a ball in spheronizator, and round as a ball capsule core is taken out after round as a ball 2.5min and is carried out
Dry, the capsule core sieving after drying weighs appropriate capsule core measurement amoxicillin content, by Ah not in immediate release section and slow-released part
The ratio in XiLin, capsule core weight needed for converting slow-released part, and it is spare to weigh；
(3) packet slow release layer: 85-95% is added slowly under the slow-release material, plasticizer and antitackiness agent of recipe quantity are stirred
In ethyl alcohol, stirring is spare to dissolution；Capsule core weighted in step (2) is placed in fluidized bed, fluidized bed, setting stream are started
Start hydrojet coating after changing bed, pastille slow-release piller is made；
(4) tabletting: by the main ingredient Amoxicillin of pastille slow-release piller obtained in step (3) and immediate release section recipe quantity,
Filler, disintegrating agent and mix lubricant it is uniform after, using direct compression method tabletting up to amoxicillin dispersible tablet.
The preparation method of above-mentioned amoxicillin dispersible tablet, hole diameter of sieve (perforated) plate 0.8mm in step (2) squeeze out revolving speed 80r/min,
Spheronizator revolving speed is 820r/min.
The preparation method of above-mentioned amoxicillin dispersible tablet, the round as a ball capsule core of the middle taking-up of step (2) carry out 40 DEG C and are dried under reduced pressure
To moisture less than 1%.
The preparation method of above-mentioned amoxicillin dispersible tablet, it is dry in step (2) after capsule core screening removal fine powder and big
Grain takes 20-24 mesh sieving capsule core, spare.
The preparation method of above-mentioned amoxicillin dispersible tablet, set in step (3) fluidized bed parameter be respectively as follows: nozzle diameter as
0.5mm, inlet air temperature be 40-45 DEG C, 30-35 DEG C of temperature of charge, atomizing pressure 0.15-0.20MPa.
Amoxicillin dispersible tablet dissolution releasing effect achieved of the present invention is prolonging for capsule core packing material microcrystalline cellulose
The slow release effect synergy of the effect and processed cashew nut natural gum of slow drug-eluting as a result, ensure that dispersible tablet 4
Hour in dissolution release completely, while in slow-released part and immediate release section Amoxicillin ratio 4:6, ensure that dispersible tablet dissolution
Release is steady and complete, finally realizes the blood concentration of product of the present invention in vivo and keeps long lasting for the water for being higher than MIC
It is flat, it ensure that the antibacterial effect of Amoxicillin, clinical efficacy significantly improve significantly, while realizing amoxicillin dispersible tablet in people
The reasonable blood concentration of the good stable state of body, also ensures the safety of medication.In addition, starch, lactose are as a kind of in capsule core
The yield of step (2) preparation capsule core can be improved in regulator, if being added without regulator, 4- is added 80% in capsule core yield
5% regulator, capsule core yield is 90% or more.
Detailed description of the invention
Fig. 1 comparative example A, comparative example B dissolve out release profiles
Influence of the ratio of Amoxicillin to dispersible tablet dissolution release behavior in Fig. 2 immediate release section and slow-released part
The amoxicillin dispersible tablet of Fig. 3 embodiment 2-4 dissolves out release profiles
Specific embodiment
Content of the present invention is described in further detail combined with specific embodiments below.
The pre-processing of embodiment 1 cashew nut natural gum
Pulverizer is added in cashew nut natural gum to crush, is sieved with the vibrating screen of 20 mesh；95% ethanol solution, sodium hydroxide and
Above-mentioned sieving crushed material is stirred 5 hours by weight the ratio of 5:0.5:1, obtains reaction solution；With in advance through the salt of 1mol/L
In the 732 type strong acid ion exchange resins that acid is handled well and above-mentioned reaction solution is to pH=7；It filters and removes resin, by filtrate decompression
Distillation and concentration is to thick；95% ethyl alcohol is added and stirs, suction filtration muddy to dispersion, the spray-dried waist refined of filtrate
Fruit gum powder, 73 DEG C of spray dryer outlet temperature of setting, 112 DEG C of inlet temperature, charging rate 10.5mL/min.
1 cashew nut natural gum of comparative experimental example before and after the processing influences amoxicillin dispersible tablet
Respectively using untreated cashew nut natural gum and the cashew nut natural gum handled by 1 method of embodiment as Sustained release coating materials system
Standby different amoxicillin dispersible tablet influences amoxicillin dispersible tablet with investigating cashew nut natural gum before and after the processing.
The untreated cashew nut natural gum of comparative example A prepares amoxicillin dispersible tablet
Prescription: 1000 are respectively made
Preparation process:
1, prepare supplementary material: supplementary material in prescription is sieved with 100 mesh sieve respectively, it is spare.
2, it prepares capsule core: main ingredient Amoxicillin, microcrystalline cellulose, starch being uniformly mixed by recipe quantity and are placed on wet process system
In grain machine, the purified water for being gradually added into recipe quantity is that softwood is made in wetting agent, softwood obtained is transferred in extruder, through squeezing
Sieve plate (aperture 0.8mm, squeeze out revolving speed 80r/min) is extruded into bar out, the bar of extrusion is transferred to it is round as a ball in spheronizator,
Revolving speed is 820r/min, and 40 DEG C round as a ball of capsule core progress is taken out after round as a ball 2.5min and is dried under reduced pressure to moisture less than 1%, after dry
Capsule core screening removal fine powder and bulky grain, take 20-24 mesh to be sieved capsule core, weigh appropriate capsule core measurement amoxicillin content, folding
Capsule core weight needed for calculating 100g main ingredient Amoxicillin, and it is spare to weigh.
3, packet slow release layer: the untreated cashew nut natural gum of recipe quantity, Macrogol 4000 and magnesium stearate stirring is lower slow
It is slow to be added in 95% ethyl alcohol, it is stirred until homogeneous, it is spare.By the ball containing 100g main ingredient Amoxicillin load weighted in step 2
Core is placed in fluidized bed, starts fluidized bed, starts hydrojet coating after setting fluidized bed, pastille slow-release piller is made.Each experiment ginseng
Number be respectively as follows: nozzle diameters be 0.5mm, inlet air temperature be 40-45 DEG C, 30-35 DEG C of temperature of charge, atomizing pressure 0.15-
0.20MPa.4, tabletting: by pastille slow-release piller obtained in step 3 and immediate release section recipe quantity main ingredient Amoxicillin, crystallite fibre
Element, sodium carboxymethyl starch and talcum powder are tieed up after mixing, using direct compression method tabletting up to amoxicillin dispersible tablet.
The processed cashew nut natural gum of comparative example B prepares amoxicillin dispersible tablet
Prescription: 1000 are respectively made
Preparation process:
1, prepare supplementary material: supplementary material in prescription is sieved with 100 mesh sieve respectively, it is spare.
2, it prepares capsule core: main ingredient Amoxicillin, microcrystalline cellulose, starch being uniformly mixed by recipe quantity and are placed on wet process system
In grain machine, the purified water for being gradually added into recipe quantity is that softwood is made in wetting agent, softwood obtained is transferred in extruder, through squeezing
Sieve plate (aperture 0.8mm, squeeze out revolving speed 80r/min) is extruded into bar out, the bar of extrusion is transferred to it is round as a ball in spheronizator,
Revolving speed is 820r/min, and 40 DEG C round as a ball of capsule core progress is taken out after round as a ball 2.5min and is dried under reduced pressure to moisture less than 1%, after dry
Capsule core screening removal fine powder and bulky grain, take 20-24 mesh to be sieved capsule core, weigh appropriate capsule core measurement amoxicillin content, folding
Capsule core weight needed for calculating 100g main ingredient Amoxicillin, and it is spare to weigh.
3, packet slow release layer: under the processed cashew nut natural gum of recipe quantity, Macrogol 4000 and magnesium stearate are stirred slowly
It is added in 95% ethyl alcohol, stirring is spare to dissolution.By the capsule core containing 100g main ingredient Amoxicillin weighted in step 2
It is placed in fluidized bed, starts fluidized bed, start hydrojet coating after setting fluidized bed, pastille slow-release piller is made.Each experiment parameter
Be respectively as follows: nozzle diameter be 0.5mm, inlet air temperature be 40-45 DEG C, 30-35 DEG C of temperature of charge, atomizing pressure 0.15-
0.20MPa。
4, tabletting: pastille slow-release piller obtained in step 3 and immediate release section recipe quantity main ingredient Amoxicillin, drug containing are delayed
Piller microcrystalline cellulose, sodium carboxymethyl starch and talcum powder are released after mixing, using direct compression method tabletting up to A Moxi
Standing forest discrete piece.
The dissolution determination of amoxicillin dispersible tablet is according to " Chinese Pharmacopoeia " version annex second method of XC in 2010, with 900mL
The water of pH6.8 is dissolution medium, revolving speed 75r/min, in 40,80,120,160,200,240,280,320,360,400,
440, it is sampled when 480min, according to the amount of dissolution of " Chinese Pharmacopoeia " the first enlarged edition of version measurement amoxicillin dispersible tablet in 2010, and
Cumulative defaultlogic is calculated, dissolution release profiles are drawn, as shown in table 1, Fig. 1.
The dissolution data of 1 comparative example A of table, comparative example B
Untreated cashew nut natural gum, is not completely soluble in 85-95% ethyl alcohol, is difficult that excellent coating solution is made and be wrapped
Clothing, and the dissolution of obtained amoxicillin dispersible tablet is too slow, comparative example A dissolved out 86.6% at 8 hours, three times a day it is administered,
When second of administration, given drug is not yet dissolved out completely for the first time, and it is unstable that this dissolved corrosion is easy blood concentration in primosome.
In addition, the dissolution curve of comparative example A is also bad, dissolve out early period quickly, slow-released part release is too slow, there is phenomenon of burst release, delays simultaneously
It releases and may cause very much internal blood concentration slowly lower than MIC, not can guarantee restraining and sterilizing bacteria effect.
Cashew nut natural gum can be dissolved in 85-95% ethyl alcohol after the processing of 1 method of embodiment, prepare by above-mentioned prescription and method
At amoxicillin dispersible tablet, inside and outside dissolution release is just able to achieve steadily long lasting for antibacterial effect, also ensures medication
Safety and validity.
Influence of 2 quick-releases of the comparative experimental example/sustained release different ratio Amoxicillin to dispersible tablet dissolution release behavior
Respectively in 4 kinds of ratio 4:6,5:5,6:4,7:3 accordings to the form below of Amoxicillin in immediate release section and slow-released part
Side prepares different amoxicillin dispersible tablets, to investigate the different proportion of Amoxicillin in immediate release section and slow-released part to dispersion
The influence of piece dissolution release behavior.
Prescription: 1000 are respectively made
Preparation process:
1, prepare supplementary material: supplementary material in prescription is sieved with 100 mesh sieve respectively, it is spare.
2, it prepares capsule core: main ingredient Amoxicillin, microcrystalline cellulose, starch being uniformly mixed by recipe quantity and are placed on wet process system
In grain machine, the purified water for being gradually added into recipe quantity is that softwood is made in wetting agent, softwood obtained is transferred in extruder, through squeezing
Sieve plate (aperture 0.8mm, squeeze out revolving speed 80r/min) is extruded into bar out, the bar of extrusion is transferred to it is round as a ball in spheronizator,
Revolving speed is 820r/min, and 40 DEG C round as a ball of capsule core progress is taken out after round as a ball 2.5min and is dried under reduced pressure to moisture less than 1%, after dry
Capsule core screening removal fine powder and bulky grain, take 20-24 mesh to be sieved capsule core, weigh appropriate capsule core measurement amoxicillin content, press
The ratio of Amoxicillin in immediate release section and slow-released part, capsule core weight needed for converting slow-released part, and it is spare to weigh.
3, packet slow release layer: under the processed cashew nut natural gum of recipe quantity, Macrogol 4000 and magnesium stearate are stirred slowly
It is added in 95% ethyl alcohol, stirring is spare to dissolution.Capsule core weighted in step 2 is placed in fluidized bed, starting fluidisation
Bed starts hydrojet coating after setting fluidized bed, pastille slow-release piller is made.Each experiment parameter is respectively as follows: nozzle diameter
0.5mm, inlet air temperature be 40-45 DEG C, 30-35 DEG C of temperature of charge, atomizing pressure 0.15-0.20MPa.
4, tabletting: by pastille slow-release piller obtained in step 3 and immediate release section recipe quantity main ingredient Amoxicillin, crystallite fibre
Element, sodium carboxymethyl starch and talcum powder are tieed up after mixing, using direct compression method tabletting up to amoxicillin dispersible tablet.
The dissolution determination of amoxicillin dispersible tablet is according to " Chinese Pharmacopoeia " version annex second method of XC in 2010, with 900mL
The water of pH6.8 is dissolution medium, revolving speed 75r/min, in 20,40,60,80,100,120,140,160,180,200,220,
It samples when 240min, according to the amount of dissolution of " Chinese Pharmacopoeia " the first enlarged edition of version measurement amoxicillin dispersible tablet in 2010, and calculates
Cumulative defaultlogic draws dissolution release profiles, as shown in table 2, Fig. 2.
2 quick-releases of table/sustained release different ratios of raw materials amoxicillin dispersible tablet dissolves out data
As shown in table 2, Fig. 2 result, when the ratio of Amoxicillin is 6:4 in immediate release section and slow-released part, Ah. of the present invention
It is the most steady that Amdinocillin dispersible tablet dissolves out release profiles, and accumulative dissolution percentage when 4h is up to 99.8%.Quick-release/sustained release Ah
Other ratio situations of Amdinocillin, dispersible tablet dissolution is unstable, and final accumulative dissolution percentage is also low, finally preferably, quick-release
The ratio of part and Amoxicillin in slow-released part is 6:4.
The preparation of 2 amoxicillin dispersible tablet of embodiment
Prescription: 1000 are made
Preparation process:
1, prepare supplementary material: supplementary material in prescription is sieved with 100 mesh sieve respectively, it is spare.
2, it prepares capsule core: main ingredient Amoxicillin 120g, microcrystalline cellulose 32g, starch 8g being uniformly mixed and are placed on wet process
In granulator, being gradually added into 40g purified water is that softwood is made in wetting agent, softwood obtained is transferred in extruder, through squeezing out
Sieve plate (aperture 0.8mm, squeeze out revolving speed 80r/min) is extruded into bar, the bar of extrusion is transferred to round as a ball in spheronizator, turns
Speed is 820r/min, and 40 DEG C round as a ball of capsule core progress is taken out after round as a ball 2.5min and is dried under reduced pressure to moisture less than 1%, after dry
Capsule core screening removal fine powder and bulky grain take 20-24 mesh sieving capsule core, weigh appropriate capsule core measurement amoxicillin content, conversion
Capsule core weight needed for 100g main ingredient Amoxicillin, and it is spare to weigh.
3, packet slow release layer: processed cashew nut natural gum 29g, Macrogol 4000 3g and magnesium stearate 6g stirring is lower slow
Slow to be added in 95% ethyl alcohol, stirring is spare to dissolution.By the ball containing 100g main ingredient Amoxicillin weighted in step 2
Core is placed in fluidized bed, starts fluidized bed, starts hydrojet coating after setting fluidized bed, pastille slow-release piller is made.Each experiment ginseng
Number be respectively as follows: nozzle diameters be 0.5mm, inlet air temperature be 40-45 DEG C, 30-35 DEG C of temperature of charge, atomizing pressure 0.15-
0.20MPa。
4, tabletting: by pastille slow-release piller obtained in step 3 and immediate release section main ingredient Amoxicillin 150g, microcrystalline cellulose
Plain 320g, sodium carboxymethyl starch 26g and talcum powder 3g disperse after mixing, using direct compression method tabletting up to Amoxicillin
Piece.
The preparation of 3 amoxicillin dispersible tablet of embodiment
Prescription: 1000 are made
Preparation process:
1, prepare supplementary material: supplementary material in prescription is sieved with 100 mesh sieve respectively, it is spare.
2, it prepares capsule core: main ingredient Amoxicillin 120g, microcrystalline cellulose 45g, lactose 7g being uniformly mixed and are placed on wet process
In granulator, being gradually added into 37g purified water is that softwood is made in wetting agent, softwood obtained is transferred in extruder, through squeezing out
Sieve plate (aperture 0.8mm, squeeze out revolving speed 80r/min) is extruded into bar, the bar of extrusion is transferred to round as a ball in spheronizator, turns
Speed is 820r/min, and 40 DEG C round as a ball of capsule core progress is taken out after round as a ball 2.5min and is dried under reduced pressure to moisture less than 1%, after dry
Capsule core screening removal fine powder and bulky grain take 20-24 mesh sieving capsule core, weigh appropriate capsule core measurement amoxicillin content, conversion
Capsule core weight needed for 100g main ingredient Amoxicillin, and it is spare to weigh.
3, packet slow release layer: processed cashew nut natural gum 38g, triethyl citrate 9g and superfine silica gel powder 12g stirring is lower slow
Slow to be added in 95% ethyl alcohol, stirring is spare to dissolution.By the ball containing 100g main ingredient Amoxicillin weighted in step 2
Core is placed in fluidized bed, starts fluidized bed, starts hydrojet coating after setting fluidized bed, pastille slow-release piller is made.Each experiment ginseng
Number be respectively as follows: nozzle diameters be 0.5mm, inlet air temperature be 40-45 DEG C, 30-35 DEG C of temperature of charge, atomizing pressure 0.15-
0.20MPa。
4, tabletting: by pastille slow-release piller obtained in step 3 and immediate release section main ingredient Amoxicillin 150g, microcrystalline cellulose
Plain 350g, cross-linked carboxymethyl cellulose receive 35g and superfine silica gel powder 4g after mixing, using direct compression method tabletting up to Ah not
XiLin dispersible tablet.
The preparation of 4 amoxicillin dispersible tablet of embodiment
Prescription: 1000 are made
Preparation process:
1, prepare supplementary material: supplementary material in prescription is sieved with 100 mesh sieve respectively, it is spare.
2, it prepares capsule core: main ingredient Amoxicillin 120g, microcrystalline cellulose 38g, lactose 8g being uniformly mixed and are placed on wet process
In granulator, being gradually added into 35g purified water is that softwood is made in wetting agent, softwood obtained is transferred in extruder, through squeezing out
Sieve plate (aperture 0.8mm, squeeze out revolving speed 80r/min) is extruded into bar, the bar of extrusion is transferred to round as a ball in spheronizator, turns
Speed is 820r/min, and 40 DEG C round as a ball of capsule core progress is taken out after round as a ball 2.5min and is dried under reduced pressure to moisture less than 1%, after dry
Capsule core screening removal fine powder and bulky grain take 20-24 mesh sieving capsule core, weigh appropriate capsule core measurement amoxicillin content, conversion
Capsule core weight needed for 100g main ingredient Amoxicillin, and it is spare to weigh.
3, packet slow release layer: under processed cashew nut natural gum 33g, Ergol 5g and superfine silica gel powder 10g are stirred slowly
It is added in 85% ethyl alcohol, stirring is spare to dissolution.By the capsule core containing 100g main ingredient Amoxicillin weighted in step 2
It is placed in fluidized bed, starts fluidized bed, start hydrojet coating after setting fluidized bed, pastille slow-release piller is made.Each experiment parameter
Be respectively as follows: nozzle diameter be 0.5mm, inlet air temperature be 40-45 DEG C, 30-35 DEG C of temperature of charge, atomizing pressure 0.15-
0.20MPa。
4, tabletting: by pastille slow-release piller obtained in step 3 and immediate release section main ingredient Amoxicillin 150g, microcrystalline cellulose
Plain 330g, crosslinked polyvinylpyrrolidone 30g and magnesium stearate 3g after mixing, using direct compression method tabletting up to Ah not
XiLin dispersible tablet.
The in vitro test of 1 amoxicillin dispersible tablet of test example
By the dissolution measuring method of amoxicillin dispersible tablet in comparative experimental example 1, the dissolution for detecting embodiment 2-4 discharges feelings
Condition, as shown in table 3, Fig. 3.
The amoxicillin dispersible tablet of 3 embodiment 2-4 of table dissolves out data
The result of extraction of 2-4 amoxicillin dispersible tablet of the embodiment of the present invention is good, the cumulative defaultlogic of release 4 hours
Reach 99.5% or more, the smooth absorption of amoxicillin dispersible tablet in vivo has been effectively ensured.
2 amoxicillin dispersible tablet in vivo studies of test example
Pharmacokinetic studies
Drug:
Sample of the present invention: the amoxicillin dispersible tablet of 2-4 method of embodiment of the present invention preparation
1 sample of comparative example: the amoxicillin dispersible tablet that patent CN200810101332.3 embodiment 1 obtains
2 sample of comparative example: the amoxicillin dispersible tablet that patent CN201110289124.2 specific embodiment obtains
3 sample of comparative example: the amoxicillin dispersible tablet that patent CN201410446830.7 embodiment 1 obtains
Commercially available reference substance: the amoxicillin dispersible tablet of Shanxi Tongda Pharmaceutical Co., Ltd., lot number 160901
Experimental method:
With reference to the article for being published in " The Chinese Journal of Clinical Pharmacology " for 2006, " amoxicillin/clavulanate potassium tablet is strong
Method in the pharmacokinetics and pharmacodynamics of Kang Renti " carries out internal pharmacokinetic trial.
Subject selection: selection male volunteers 10, average age (21.33 soil 1.12) year, height (175.09 soil
3.67) cm, weight (68.32 soil 7.81) kg.Without beta-lactam class antibiotic allergies, drug test was not participated in 4 months.
Before testing in 72h, complete physical examination is carried out, detection blood, routine urinalysis, blood biochemistry index are normal, normal ECG；Experimental period
Between, quit smoking, wine.
Dosage regimen: 10 health volunteers fasting 12h before being administered tests the same day, gives Amoxicillin dispersion respectively
Piece 500mg is taken with warm water 250mL；4h after administration gives unified standard meal；Tested period, drinking-water are appropriate；It tests when morning 8
Left and right starts.
Collection of specimens: before administration and 0.25,0.50,0.75,1,1.5,2,3,4,5,6,8,10h after administration,
Upper limb ulnar vein takes blood 3.5mL, stands 5min, and 3000r/min is centrifuged 10min, separates serum, and sample is set -40 DEG C of refrigerators and saved
To measurement.
Internal pharmacokinetic trial is carried out respectively to embodiment 2-4, comparative example 1-3, commercially available product sample, using microorganism
Method measures sample, acquires in each sample Amoxicillin blood concentration through processing and main separates pathogenic bacteria MIC relationship, such as table with clinical
Shown in 4.
4 each sample Amoxicillin blood concentration of table mainly separates pathogenic bacteria MIC relationship with clinical
Amoxicillin dispersible tablet of the present invention starts to discharge a part of Amoxicillin and reaches expected blood concentration, rapid-onset,
It will continue to the remaining Amoxicillin of slow release below, maintain drug concentration to be always held on MIC for a long time, persistently have
Effect.Amoxicillin is time-dependent antibiotic, cannot inhibit bacterial growth when concentration is lower than MIC, when concentration reaches MIC,
Bacterium can be effectively killed, is further continued for increasing blood concentration, bactericidal effect will not be further added by.Thus T > MIC is prediction beta-lactam
The key parameter of class antibiotic clinical efficacy, when the time that T > MIC accounts for dosing interval is 20% or lower, the death rate is
100%；Work as T > MIC is increased to dosing interval 35%~40%, antibacterial action enhancing, count plate significantly reduces；And work as T >
When the time that MIC accounts for dosing interval meets or exceeds 40%~50%, bacteriological identification treats mesh up to 90%~100%
Be exactly to make drug " T > MIC " >=4O%.
According to embodiment 2-4 test data in table 4, for streptococcus pneumonia, Amoxicillin blood concentration is more than the time of MIC
About 5.1-5.3h, if being administered 3 times a day, T > MIC accounts for the 63.8%-66.3% of 8h dosing interval；For bloodthirsty influenza bar
Bacterium, it is about 4.0-4.2h that Amoxicillin blood concentration, which is more than the time of MIC, accounts for the 50.0%-52.5% of 8h dosing interval；For
Methicillin Sensitive Staphylococcus aureus, it is about 4.3-4.4h that Amoxicillin blood concentration, which is more than the time of MIC, accounts for 8h administration
The 55.0%-53.8% at interval；For staphylococcus epidermis, it is about 5.0- that Amoxicillin blood concentration, which is more than the time of MIC,
5.1h accounts for the 62.5%-63.8% of 8h dosing interval；For penicillin resistance pneumococcus, Amoxicillin blood concentration is more than
The time of MIC is about 3.2-3.3h, accounts for the 40.0%-41.3% of 8h dosing interval；For moraxelle catarrhalis and suppurative hammer
Bacterium, it is more than 8h that Amoxicillin blood concentration, which is more than the time of MIC, accounts for the 100% of 8h dosing interval.
By 4 result of table as it can be seen that the sample of embodiment 2-4 for streptococcus pneumonia, bloodthirsty Bacillus influenzae, moraxelle catarrhalis,
Methicillin Sensitive Staphylococcus aureus, staphylococcus epidermis, micrococcus scarlatinae and enterococcus faecalis, T > MIC account for 8h administration
Interval may remain in vivo 50% or more, that is, before administration next time long lasting for effective.And comparative example 1-3,
The sample of commercially available product is only to streptococcus pneumonia, staphylococcus epidermis, and T > MIC accounts for 8h dosing interval 40% or more, but to it
His several germs, T > MIC accounts for 8h dosing interval 30% or so, that is, is unable to continuous and effective, is also less than and takes medicine next time
Effect, internal blood concentration are lower than MIC.In addition, the present invention has surprisingly been found that, product designed by the present invention is for penicillin resistant
Streptococcus pneumonia, T > MIC account for 8h dosing interval also 40% or more, also achieve continuous and effective, in this way this invention also solves
Penicillin-resistant problem.
From the above it is found that amoxicillin dispersible tablet of the present invention release is steady, and continuous and effective in vivo, compared with comparative example
And commercially available product, drug effectiveness are more excellent.
Claims (9)
1. a kind of amoxicillin dispersible tablet, which is characterized in that ratio of the main ingredient Amoxicillin with weight ratio for 4:6 is distributed in sustained release
Part and immediate release section；The slow-released part be by sustained release coating liquid spraying be at least containing microcrystalline cellulose packing material ball
Core is constituted；Slow-release material is processed cashew nut natural gum in the sustained release coating liquid；The immediate release section is by filler, disintegrating agent
It is prepared with lubricant；The filler is microcrystalline cellulose, and the disintegrating agent is selected from sodium carboxymethyl starch, cross-linked carboxymethyl
Cellulose one or both of is received with crosslinked polyvinylpyrrolidone, and the lubricant is selected from magnesium stearate, talcum powder and micro-
One or both of powder silica gel.
2. amoxicillin dispersible tablet according to claim 1, which is characterized in that the capsule core by main ingredient Amoxicillin with fill out
It fills material to be made of extrusion spheronization method, wherein packing material also contains one or both of starch and lactose；The sustained release
Coating solution is to dissolve processed cashew nut natural gum, plasticizer, antitackiness agent with 85-95% ethanol solution to be made；Wherein, plasticizer selects
From one or both of Macrogol 4000, triethyl citrate and Ergol, antitackiness agent is selected from magnesium stearate or micro-
Powder silica gel.
3. amoxicillin dispersible tablet according to claim 1, which is characterized in that the crystallite in the capsule core packing material is fine
The weight ratio of dimension element and processed cashew nut natural gum is 1:1.02-1.08.
4. amoxicillin dispersible tablet according to claim 1, which is characterized in that the processed cashew nut natural gum, place
Reason method is as follows:
Cashew nut tree rubber pulverizing is crossed into 20 meshes；95% ethyl alcohol, sodium hydroxide and above-mentioned sieving crushed material is by weight 5:0.5:1
Stirring 5 hours, obtains reaction solution；With in 732 type strong acid ion exchange resins and above-mentioned reaction solution is to pH=7；It filters and removes resin,
By filtrate decompression distillation and concentration to thick；95% ethyl alcohol is added and stirs, suction filtration muddy to dispersion, filtrate is spray-dried to obtain the final product
To processed cashew nut natural gum；Wherein, the setting condition of the spray drying: 73 DEG C of outlet temperature, 112 DEG C of inlet temperature, into
Expect speed 10.5mL/min.
5. amoxicillin dispersible tablet according to claim 1, which is characterized in that every 1000 prepared by following supplementary material and
At:
Wherein, slow-released part capsule core dosage need to be converted, also in the ratio 4:6 of Amoxicillin in slow-released part and immediate release section
It is to need the capsule core containing 100g main ingredient Amoxicillin.
6. amoxicillin dispersible tablet according to claim 1, which is characterized in that every 1000 prepared by following supplementary material and
At:
Wherein, slow-released part capsule core dosage need to be converted, also in the ratio 4:6 of Amoxicillin in slow-released part and immediate release section
It is to need the capsule core containing 100g main ingredient Amoxicillin.
7. amoxicillin dispersible tablet according to claim 1, which is characterized in that every 1000 prepared by following supplementary material and
At:
Wherein, slow-released part capsule core dosage need to be converted, also in the ratio 4:6 of Amoxicillin in slow-released part and immediate release section
It is to need the capsule core containing 100g main ingredient Amoxicillin.
8. a kind of method for preparing amoxicillin dispersible tablet described in claim 1 to 7 any claim, which is characterized in that
Include the following steps:
(1) prepare supplementary material: supplementary material in prescription is sieved with 100 mesh sieve respectively, it is spare；
(2) it prepares capsule core: the main ingredient Amoxicillin of recipe quantity being uniformly mixed with packing material and is placed in wet granulator, by
The purified water that recipe quantity is gradually added is that softwood is made in wetting agent, and softwood obtained is transferred in extruder, sieve plate is squeezed out and squeezed
Object into strips, the bar of extrusion is transferred to round as a ball in spheronizator, and round as a ball capsule core is taken out after round as a ball 2.5min and is dried,
Capsule core sieving after drying weighs appropriate capsule core measurement amoxicillin content, by Amoxicillin in immediate release section and slow-released part
Ratio, capsule core weight needed for converting slow-released part, and it is spare to weigh；
(3) packet slow release layer: 85-95% ethyl alcohol is added slowly under the slow-release material, plasticizer and antitackiness agent of recipe quantity are stirred
In, stirring is spare to dissolution；Capsule core weighted in step (2) is placed in fluidized bed, fluidized bed is started, sets fluidized bed
After start hydrojet coating, be made pastille slow-release piller；
(4) tabletting: by the main ingredient Amoxicillin of pastille slow-release piller obtained in step (3) and immediate release section recipe quantity, filling
Agent, disintegrating agent and mix lubricant it is uniform after, using direct compression method tabletting up to amoxicillin dispersible tablet.
9. the method according to claim 8 for preparing amoxicillin dispersible tablet, which is characterized in that hole diameter of sieve (perforated) plate in step 2
0.8mm, squeezes out revolving speed 80r/min, and spheronizator revolving speed is 820r/min；Round as a ball capsule core is taken out in step 2 carries out 40 DEG C of decompressions
Drying is to moisture less than 1%；Capsule core screening removal fine powder and bulky grain in step 2 after drying, take 20-24 mesh sieving capsule core,
It is spare；Fluidized bed parameter is set in step 3 and is respectively as follows: nozzle diameter as 0.5mm, and inlet air temperature is 40-45 DEG C, temperature of charge
30-35 DEG C, atomizing pressure 0.15-0.20MPa.
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Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995020946A1 (en) * | 1994-02-04 | 1995-08-10 | Smithkline Beecham Plc | Bilayered amoxycillin tablets |
| CN1373664A (en) * | 1999-04-13 | 2002-10-09 | 比彻姆药品(Pte)有限公司 | Therapeutic method |
| CN1382040A (en) * | 1999-04-13 | 2002-11-27 | 比彻姆药品(Pte)有限公司 | Therapeutic method |
| US20030224049A1 (en) * | 2000-10-12 | 2003-12-04 | Beecham Pharmaceuticals (Pte) Limited | Novel formulation |
| CN1460476A (en) * | 2003-06-08 | 2003-12-10 | 胡秀爱 | Apomorphine sublingual dripping pill preparation with adjustable medicine-releasing rate |
| WO2008142627A2 (en) * | 2007-05-17 | 2008-11-27 | Ranbaxy Laboratories Limited | Multilayered modified release formulation comprising amoxicillin and clavulanate |
| CN101500542A (en) * | 2006-07-11 | 2009-08-05 | 共有药物有限公司 | Controlled-release formulations |
| CN102397262A (en) * | 2010-09-15 | 2012-04-04 | 重庆医药工业研究院有限责任公司 | Amoxicillin sustained release solid medicinal composition and preparation method thereof |
| CN102861015A (en) * | 2011-07-05 | 2013-01-09 | 北京乐维生物技术有限公司 | Stable amoxicillin and clavulanate potassium sustained release preparation and preparation technology |
| WO2017013682A1 (en) * | 2015-07-20 | 2017-01-26 | Pawar Harshal Ashok | Process of preparation of co-processed polymer and it's pharmaceutical application |
-
2018
- 2018-11-15 CN CN201811359550.7A patent/CN109394718B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995020946A1 (en) * | 1994-02-04 | 1995-08-10 | Smithkline Beecham Plc | Bilayered amoxycillin tablets |
| CN1373664A (en) * | 1999-04-13 | 2002-10-09 | 比彻姆药品(Pte)有限公司 | Therapeutic method |
| CN1382040A (en) * | 1999-04-13 | 2002-11-27 | 比彻姆药品(Pte)有限公司 | Therapeutic method |
| US20030224049A1 (en) * | 2000-10-12 | 2003-12-04 | Beecham Pharmaceuticals (Pte) Limited | Novel formulation |
| CN1460476A (en) * | 2003-06-08 | 2003-12-10 | 胡秀爱 | Apomorphine sublingual dripping pill preparation with adjustable medicine-releasing rate |
| CN101500542A (en) * | 2006-07-11 | 2009-08-05 | 共有药物有限公司 | Controlled-release formulations |
| WO2008142627A2 (en) * | 2007-05-17 | 2008-11-27 | Ranbaxy Laboratories Limited | Multilayered modified release formulation comprising amoxicillin and clavulanate |
| CN102397262A (en) * | 2010-09-15 | 2012-04-04 | 重庆医药工业研究院有限责任公司 | Amoxicillin sustained release solid medicinal composition and preparation method thereof |
| CN102861015A (en) * | 2011-07-05 | 2013-01-09 | 北京乐维生物技术有限公司 | Stable amoxicillin and clavulanate potassium sustained release preparation and preparation technology |
| WO2017013682A1 (en) * | 2015-07-20 | 2017-01-26 | Pawar Harshal Ashok | Process of preparation of co-processed polymer and it's pharmaceutical application |
Non-Patent Citations (7)
| Title |
|---|
| ADEYANJU O. ET AL: "PHYSICOCHEMICAL AND BINDING PROPERTIES OF OXIDIZED Anacardium occidentale. Linn EXUDATE GUM IN PARACETAMOL TABLET FORMULATIONS", 《AFRICAN JOURNAL OF NATURAL SCIENCES》 * |
| BIPIN R GANDHI ET AL: "Development and in vitro evaluation of multiparticulate system using novel coating material for controlled drug delivery system", 《INTERNATIONAL JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES》 * |
| FU QIANG ET AL: "Once-daily amoxicillin immediate- and extended-release bilayer tablets", 《POWDER TECHNOLOGY》 * |
| RIBEIRO ANTNIO J. ET AL: "Gums’ based delivery systems: Review on cashew gum and its derivatives", 《CARBOHYDRATE POLYMERS》 * |
| ROHIT R. BHOSALE ET AL: "FORMULATION AND EVALUATION OF SUSTAINED RELEASE DOSAGE FORM USING MODIFIED CASHEW GUM", 《INTERNATIONAL JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES》 * |
| 史一杰等: "阿莫西林双相释药双层片的制备及释放度研究", 《北方药学》 * |
| 林草: "腰果树胶的粘性分析", 《世界热带农业信息》 * |
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