CN104983692A - Amoxicillin slow release pellet and preparation method thereof - Google Patents
Amoxicillin slow release pellet and preparation method thereof Download PDFInfo
- Publication number
- CN104983692A CN104983692A CN201510420527.4A CN201510420527A CN104983692A CN 104983692 A CN104983692 A CN 104983692A CN 201510420527 A CN201510420527 A CN 201510420527A CN 104983692 A CN104983692 A CN 104983692A
- Authority
- CN
- China
- Prior art keywords
- amoxicillin
- plasticizer
- isolation coat
- micropill
- release
- 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.)
- Pending
Links
Abstract
The invention discloses an amoxicillin slow release pellet. The amoxicillin slow release pellet is composed of a drug-containing pellet core, an isolation coating layer and a slow release coating layer from inside to outside; and the drug-containing pellet core is composed of 50.0-95.0wt% of amoxicillin, 0.5-5.0wt% of an adhesive, 0.5-5.0wt% of a flow aid and 4.0-40.0wt% of a filler. Slow release pellets of the above amoxicillin slow release pellet preparation are composed of pellets with different drug release rates, the drug release rates can reach zero order, and no time lag phenomenon exists. A multi-dosage dosage form is difficultly influenced by the rhythm of the alimentary canal, and interference of the gastric emptying rate can be neglected. The drug content of the amoxicillin slow release pellets is 1% ~ above 95%, and the maximum dosage in a single capsule can reach 600mg and is far greater than that of other drug dosage forms.
Description
Technical field
The present invention relates to technical field of medicine, particularly relate to a kind of amoxicillin slow release micropill and preparation method thereof.
Background technology
Amoxicillin (amoxicillion) is a kind of semi-synthetic penicillins medicine, and its chemical constitution contains amino side chain, than light bases many in the side-chain benzene ring of ampicillin, so the two Nature comparison is similar.Its antimicrobial spectrum and antibacterial activity substantially identical with ampicillin, but its acid resistance comparatively ampicillin is strong, its bactericidal action comparatively the latter is strong and rapidly.Half-life is about 1 hour.Amoxicillin is stablized in acid condition, and gastrointestinal absorption rate reaches 90%, and comparatively ampicillin absorbs more rapidly completely.
Amoxicillin structural formula:
At present, on the market the amoxicillin of public offering mainly contain tablet, capsule, granule, etc. dosage form.The invention discloses a kind of preparation method of amoxicillin slow release micropill, the pastille micropill content of preparation is higher than 65%, and the content of fast release micropill is lower than 35%.Fast release micropill and pastille micropill used in combination, avoids the blank phase in early stage after medication, discharges rapidly, arrive the blood drug level needed after making medicine arrive human body.
Summary of the invention
It is short that amoxicillin slow release micropill that the present invention proposes and preparation method thereof solves drug treating time, the Wave crest and wave trough problem of medicine.
The present invention adopts following technical scheme:
Amoxicillin slow release micropill of the present invention is made up of band pill core, isolation coat layer and sustained-release coating layer from inside to outside; Band pill core is made up of amoxicillin, binding agent, fluidizer and filler, and its concrete percentage by weight is composed as follows:
Described binding agent is hydroxypropyl methylcellulose or methylcellulose; Described fluidizer is Pulvis Talci; Described filler is one or more in microcrystalline Cellulose, dextrin, starch, lactose, sucrose, PVP, ethanol, hydroxypropyl emthylcellulose.
Described isolation coat layer is by isolation coat material, antitackiness agent, plasticizer and solvent composition, and its concrete percentage by weight is composed as follows:
Wherein, isolation coat material is HPMC or polyvinyl alcohol; Antitackiness agent is Pulvis Talci; Plasticizer is dimethyl phthalate, this dimethyl ester, Polysorbate; Solvent is purified water and/or ethanol.
Described sustained-release coating layer is made up of coating materials, delayed release substrate, gastrointestinal tract adhesive agent, porogen and plasticizer; Its concrete percentage by weight is composed as follows:
Wherein, delayed release substrate mainly contains ethyl cellulose, polypropylene polysiloxanes etc.; Gastrointestinal tract adhesive agent mainly contains one or more in carbomer, methylcellulose, gelatin pectin; Plasticizer mainly contains one or more in phthalic acid ester, polrvinyl chloride, Polyethylene Glycol, poly-Pyrusussuriensis fat; Porogen mainly contains hydrophilic liquid carrier, electrolyte, saccharide, surfactant, macromolecule, microcrystalline Cellulose, a small amount of hydrophilic gel.
The weight of sustained-release coating layer is containing pill core 10% ~ 100%.
The concrete steps of the preparation method of amoxicillin slow release micropill of the present invention are as follows:
(1), the preparation of wet feed:
Medicine is mixed homogeneously with fluidizer, filler, adds adhesive, powder is made there is certain plastic moistening uniform material, or wet feed is made wet granular through comminutor;
Extrusion process: be placed in extruder by the plasticity wet feed made or wet grain, the fashion of extrusion such as to roll by wet feed by the hole of tool certain diameter or sieve through screw propulsion or rolling, is squeezed into cylindrical strip extrudate;
(2), round as a ball one-tenth ball process:
Be discharged on the rotation friction plate of spheronizator by above-mentioned extrudate heap, extrudate is then dispersed into the less cylinder that length is equivalent to its diameter, and due to the effect of frictional force, these plastic cylindrical materials ceaselessly roll onboard, are rolled into spheroidal gradually;
Round as a ball process can distinguish several different stage according to shape of particle, round as a ball one-tenth ball process is by initial short cylindrical shape particle, edge friction plate become under rotary rolling gradually without corner angle is circular cylinder, and then be rolled into dumb-bell shape, oval, until become spherical completely, another becomes ball mechanism, namely time round as a ball after the cylinder forming edge rounding, cylinder bends, reverse, subsequently cylinder break formation two be separated part, the face that both tool one is round and flat, due to the effect of revolving force and frictional force, above-mentioned planar recess, as the cave that same flower is formed, then edge bag stack be rolled into spherical,
(3), the drying of piller:
Extrude the final step that a spheronization prepares piller, drying mode mainly comprises: 1. dry under room temperature, 2. put baking oven inner drying, 3. fluid bed (under evaporating temperature), drying is lyophilization 4., and 5. microwave oven is dry;
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer;
Quality containing pill core is the 10.0-95.0% of micropill gross mass
The quality of isolation coat layer is the 0-10.0% containing pill core
The quality of sustained-release coating layer is the 10.0-100.0% containing pill core
Mainly comprise containing pill core component: amoxicillin, adhesive, fluidizer, filler;
Common containing pill core component content: amoxicillin 55.0-95.0%, adhesive 1.5-4.0%, fluidizer 0.5-5%, filler 4.0-40%;
Optimum containing pill core component content: amoxicillin 70.0-90.0%, adhesive 2.5-4.0%, fluidizer 0.9-4.0%, filler 10.0-25.0%;
Isolation coat layer mainly comprises: isolation coat material, antitackiness agent, plasticizer, solvent
Common isolation coat layer component content: isolation coat material 5.0-10.0%, antitackiness agent 1.5-9.0%, plasticizer 0.5-5%, solvent 75.0-90.0%
Improve isolation coat layer component content: isolation coat material 5.0-8.0%, antitackiness agent 2.0-6.0%, plasticizer 1.0-5.0%, solvent 82.0-90.0%
Optimum isolation coat layer component content: isolation coat material 6.0-8.0%, antitackiness agent 3.0-5.0%, plasticizer 2.0-4.0%, solvent 83.0-90.0%
Sustained-release coating layer mainly comprises: coating materials, delayed release substrate, plasticizer, porogen, gastrointestinal tract adhesive agent;
Common isolation coat layer component content: coating materials 55.0-82.7%, delayed release substrate 15.0-30.0%, plasticizer 0.5-5.0%, porogen 1.5-6.0%, gastrointestinal tract adhesive agent 0.3-6.0%
Improve isolation coat layer component content: coating materials 60.0-82.7%, delayed release substrate 17.0-25.0%, plasticizer 0.5-5.0%, porogen 1.5-5.0%, gastrointestinal tract adhesive agent 1.0-5.0%
Optimum isolation coat layer component content: coating materials 70.0-80.0%, delayed release substrate 20.0-25.0%, plasticizer 1.0-3.0%, porogen 2.0-4.0%, gastrointestinal tract adhesive agent 1.0-3.0%.
Slow-release micro-pill containing amoxicillin of the present invention, targeted sustained release pastille micropill content is higher than 65%, the content of fast release micropill is lower than 35%, and wherein slow release pastille micropill is sustained-release coating layer from outside to inside successively and contains pill core, and wherein the weight of sustained-release coating layer is 10% ~ 100% containing pill core.Preferred coating weight gain 10 ~ 40%.The key of controlled release fertilizer micropill drug release patterns of the present invention is the weightening finish of sustained-release coating layer, when coatings weightening finish lower than 10% time, within 3 hours, accumulation drug release rate reaches more than 90%, can not embody slow release effect, but when coating weight gain is more than 100%, slow release is too slow, is not suitable for clinical practice.
Method of extruding and kneading to pellets (extrusion-spheronization) is the method preparing the most extensive use of pilule at present.Refer to and medicine, adjuvant powder are added adhesive mix homogeneously, by extruder, it is extruded into bar column, then in spheronizator, cylindrical material is cut, be rolled onto even, regular spherical of size, finally carry out drying, coating.
This method is a kind of more novel pill method, and foreign literature often can be seen, even with this method gained even particle size, narrow particle size distribution, medicament contg.Required device mainly contains extruder and spheronizator.Wet stock after extruder can make kneading is extruded into cylindrical, and spheronizator can make to extrude cylindrical material and be rolled onto spherical.It has: granulation time short (batch of material only needs 3 minutes) and yield rate high (yield rate can reach 100% substantially) without the need to screening, particle diameter scalable, the advantage such as uniform component distribution in spherolite.
The sustained-release pellet preparation of amoxicillin of the present invention, slow-release micro-pill is made up of the piller of different rate of releasing drug, and rate of releasing drug can reach zero level, and without time delay.Multiple agent type is not subject to the impact of the digestive tract rhythm and pace of moving things, can ignore the interference of gastric emptying rate.Amoxicillin slow release micropill pastille scope, can from more than 1% to 95%, and the maximal dose in single capsule can reach 600mg, much larger than other medicines dosage form.The advantage of slow-release micro-pill has: 1, micropill take after can extensively, be evenly distributed in intestinal, decentralized because dosage inclines, medicine increases at the area of gastrointestinal tract surface distributed, improves bioavailability, decreases local irritation; 2, the impact of the transhipment unable to take food thing conveying rhythm and pace of moving things of micropill in gastrointestinal tract; 3, the drug release behavior of slow release or controlled release micro pill is the summation of each micropill drug release behavior of a composition dosage, the error of indivedual piller in preparation or the unlikely drug release behavior to overall preparation of defect produce and have a strong impact on, and at this, we set one day by experiment and are administered once.
The present invention's said technical scheme empirical tests possesses following advantage and good effect:
(1), HPLC analytic process is stable accurately, show that amoxicillin slow release preparation is feasible by physicochemical property.
(2), the amoxicillin of different drug level do not make significant difference in the absorption of the full intestinal of rat, and the absorption of medicine is first order kinetics process, and mechanism of absorption is Passive diffusion; Amoxicillin absorbs slowly in intestinal, by some perforating agents of interpolation, gastrointestinal tract adhesive agent, amoxicillin slow release micropill effectively can promote that amoxicillin is in the absorption of rat small intestine.
(3), adopt and extrude-spheronization technique, the amoxicillin slow release micropill prepared by slow-release material, its tablets in vitro is slow, lasting, steady.
(4) be, with EC major coat material, HPMC is the amoxicillin slow release coated micropill that porogen obtains, and release slowly, is the drug release mode that diffusion and solutional phase combine.
(5), HPMC as gel matrix tablet main material, its consumption is the determiner of release.
(6), in vivo micropill have certain slow releasing function compared with tablet, improve drug treating time, effectively reduce drug toxicity.
Accompanying drawing explanation
Fig. 1 is that amoxicillin slow release micropill of the present invention compares with the release profiles of common Wymox
Fig. 2 is embodiment 1 amoxicillin slow release micropill release profiles
Fig. 3 is embodiment 2 amoxicillin slow release micropill release profiles
Fig. 4 is embodiment 3 amoxicillin slow release micropill release profiles
Fig. 5 is embodiment 4 amoxicillin slow release micropill release profiles
Fig. 6 is embodiment 5 amoxicillin slow release micropill release profiles
Fig. 7 is embodiment 6 amoxicillin slow release micropill release profiles
Fig. 8 is embodiment 7 amoxicillin slow release micropill release profiles
Fig. 9 is embodiment 8 amoxicillin slow release micropill release profiles
Amoxicillin slow release micropill effective drug duration of the present invention reaches 24 hours as can be seen from Figure 1, and the effective drug duration of common Wymox only has 3 hours.
Fig. 2-9 is the amoxicillin slow release micropill obtained by the different prescription content of the present invention, as can be seen from the figure so the effective drug duration of micropill is all close to 24 hours, is much better than ordinary preparation.
Detailed description of the invention
The raw material of amoxicillin solution is as follows: amoxicillin 100g, propylene glycol 100ml, water 400ml;
Embodiment 1:
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer
Preparation containing pill core:
1, sieve: 40 eye mesh screens crossed by amoxicillin, filler, binding agent and fluidizer
2, mix: accurately take that the amoxicillin 70g, the binding agent that have sieved are methylcellulose 4g, fluidizer is Pulvis Talci 1g, filler is microcrystalline Cellulose 10g, dextrin 15g is placed in mixer mix homogeneously
3, sit wetting agent with 75% alcoholic solution and extrude rotating speed 90r/min by carrying out extrusion spheronization after mixture moistening, round as a ball rotating speed 1000r/min, round as a ball time 6min, obtained soft material be dry at 45 DEG C, sieve, must pill core be contained
The preparation of isolation coat layer:
1, prepare coating solution: add in the purified water in stirring by isolation coat liquid polyvinyl alcohol 5g, plasticizer benzene dimethyl ester 1g, stir and make it dissolve completely.
2, stir: antitackiness agent Pulvis Talci 1g is added homogenizing in purified water, average is complete to add suspension in coating solution prepared by step 1, continues to stir.
3, use fluid bed to carry out hydrojet coating to containing pill core, obtain isolation piller.
The preparation of sustained-release coating layer:
1, sustained release coating liquid is prepared: by Sustained release coating materials triethyl citrate 10g, Sulisi 5g, porogen PEG6000 1g, lactose 1g, antitackiness agent aluminium stearate 1g, Pulvis Talci 4g, gastrointestinal tract adhesive agent gathers carboxy vinyl Doutrate 2g, hydroxypropyl methylcellulose 2g adds in the purified water in stirring, stirring makes it dissolve completely, forms the coating solution of solid content 10%.
2, fluid bed is used to carry out hydrojet coating to isolation piller.
3, coating solution stirring is maintained, the pill core 100 grams that carries obtained above being got by fluid bed sprays coating with carrying out, coating process parameters comprises coating temperature 25 DEG C, atomizing pressure 0.1MPa, and blower frequency is 30Hz, constant flow pump hydrojet speed 1.0 ± 0.1ml/min.Coating solution consumption is 30g, and coating terminates rear taking-up micropill in 40 DEG C of solidification 24h, and take out, obtain amoxicillin slow release micropill, product yield is more than 90%, obtains slow-release micro-pill.
Embodiment 2
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer containing the preparation of pill core:
1, sieve: 40 eye mesh screens crossed by amoxicillin, filler, binding agent and fluidizer.
2, mix: accurately take that the amoxicillin 65g, the binding agent that have sieved are methylcellulose 5g, fluidizer is Pulvis Talci 1g, filler is microcrystalline Cellulose 10g, sucrose 4g, dextrin 15g are placed in mixer mix homogeneously.
3, sit wetting agent with 75% alcoholic solution and extrude rotating speed 100r/min by carrying out extrusion spheronization after mixture moistening, round as a ball rotating speed 1200r/min, round as a ball time 7min, obtained soft material at 50 DEG C dry 4h, sieve, must pill core be contained.
The preparation of isolation coat layer:
1, prepare coating solution: add in the purified water in stirring by isolation coat liquid polyvinyl alcohol 4g, plasticizer benzene dimethyl ester 2g, stir and make it dissolve completely.
2, stir: antitackiness agent Pulvis Talci 1g is added homogenizing in purified water, average is complete to add suspension in coating solution prepared by step 1, continues to stir.
3, use fluid bed to carry out hydrojet coating to containing pill core, obtain isolation piller.
The preparation of sustained-release coating layer:
1, sustained release coating liquid is prepared: by Sustained release coating materials triethyl citrate 15g, porogen PEG6000 2g, antitackiness agent aluminium stearate 4g, Pulvis Talci 1g, gastrointestinal tract adhesive agent gathers carboxy vinyl Doutrate 5g, hydroxypropyl methylcellulose 1g adds in the purified water in stirring, stirring makes it dissolve completely, forms the coating solution of solid content 10%.
2, fluid bed is used to carry out hydrojet coating to isolation piller.
3, coating solution stirring is maintained, the pill core 100 grams that carries obtained above being got by fluid bed sprays coating with carrying out, coating process parameters comprises coating temperature 30 DEG C, atomizing pressure 0.1MPa, and blower frequency is 30Hz, constant flow pump hydrojet speed 1.2 ± 0.1ml/min.Coating solution consumption is 30g, and coating terminates rear taking-up micropill in 45 DEG C of solidification 24h, and take out, obtain amoxicillin slow release micropill, product yield is more than 91%, obtains slow-release micro-pill.
Embodiment 3
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer
Preparation containing pill core:
1, sieve: 40 eye mesh screens crossed by amoxicillin, filler, binding agent and fluidizer.
2, mix: accurately take that the amoxicillin 60g, the binding agent that have sieved are methylcellulose 5g, fluidizer is Pulvis Talci 1g, filler is sucrose 44g, dextrin 20g is placed in mixer mix homogeneously.
3, sit wetting agent with 75% alcoholic solution and extrude rotating speed 100r/min by carrying out extrusion spheronization after mixture moistening, round as a ball rotating speed 1200r/min, round as a ball time 5min, obtained soft material at 45 DEG C dry 4h, sieve, must pill core be contained.
The preparation of isolation coat layer:
1, prepare coating solution: add in the purified water in stirring by isolation coat liquid polyvinyl alcohol 5g, stir and make it dissolve completely.
2, stir: antitackiness agent Pulvis Talci 1g is added homogenizing in purified water, average is complete to add suspension in coating solution prepared by step 1, continues to stir.
3, use fluid bed to carry out hydrojet coating to containing pill core, obtain isolation piller.
The preparation of sustained-release coating layer:
1, sustained release coating liquid is prepared: by Sustained release coating materials triethyl citrate 15g, porogen PEG6000 5g, antitackiness agent aluminium stearate 3g, gastrointestinal tract adhesive agent hydroxypropyl methylcellulose 5g adds in the purified water in stirring, stirring makes it dissolve completely, forms the coating solution of solid content 10%.
2, fluid bed is used to carry out hydrojet coating to isolation piller.
3, coating solution stirring is maintained, the pill core 100 grams that carries obtained above being got by fluid bed sprays coating with carrying out, coating process parameters comprises coating temperature 30 DEG C, atomizing pressure 0.12MPa, and blower frequency is 30Hz, constant flow pump hydrojet speed 1.2 ± 0.1ml/min.Coating solution consumption is 35g, and coating terminates rear taking-up micropill in 45 DEG C of solidification 24h, and take out, obtain amoxicillin slow release micropill, product yield is more than 92%, obtains slow-release micro-pill.
Embodiment 4
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer
Preparation containing pill core:
1, sieve: 40 eye mesh screens crossed by amoxicillin, filler, binding agent and fluidizer.
2, mix: accurately take that the amoxicillin 55g, the binding agent that have sieved are methylcellulose 3g, fluidizer is Pulvis Talci 2g, filler is microcrystalline Cellulose 30g, sucrose 10g is placed in mixer mix homogeneously.
3, sit wetting agent with 75% alcoholic solution and extrude rotating speed 100r/min by carrying out extrusion spheronization after mixture moistening, round as a ball rotating speed 1200r/min, round as a ball time 6min, obtained soft material at 45 DEG C dry 3h, sieve, must pill core be contained.
The preparation of isolation coat layer:
1, prepare coating solution: isolation coat liquid polyvinyl alcohol 5g, plasticizer are gathered Pyrusussuriensis fat 1g and add in the purified water in stirring, stir and make it dissolve completely.
2, stir: antitackiness agent Pulvis Talci 1g is added homogenizing in purified water, average is complete to add suspension in coating solution prepared by step 1, continues to stir.
3, use fluid bed to carry out hydrojet coating to containing pill core, obtain isolation piller.
The preparation of sustained-release coating layer:
1, sustained release coating liquid is prepared: by Sustained release coating materials triethyl citrate 15g, porogen PEG6000 2g, antitackiness agent aluminium stearate 2g, Pulvis Talci 3g, gastrointestinal tract adhesive agent gathers carboxy vinyl Doutrate 4g and adds in the purified water in stirring, stirring makes it dissolve completely, forms the coating solution of solid content 10%.
2, fluid bed is used to carry out hydrojet coating to isolation piller.
3, coating solution stirring is maintained, the pill core 105 grams that carries obtained above being got by fluid bed sprays coating with carrying out, coating process parameters comprises coating temperature 25 DEG C, atomizing pressure 0.12MPa, and blower frequency is 30Hz, constant flow pump hydrojet speed 0.9 ± 0.1ml/min.Coating solution consumption is 40g, and coating terminates rear taking-up micropill in 45 DEG C of solidification 24h, and take out, obtain amoxicillin slow release micropill, product yield is more than 93%, obtains slow-release micro-pill.
Embodiment 5:
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer
Preparation containing pill core:
1, sieve: 40 eye mesh screens crossed by amoxicillin, filler, binding agent and fluidizer
2, mix: accurately take that the amoxicillin 65g, the binding agent that have sieved are methylcellulose 1g, fluidizer is Pulvis Talci 1g, filler is microcrystalline Cellulose 10g, sucrose 15g, dextrin 8g are placed in mixer mix homogeneously
3, sit wetting agent with 75% alcoholic solution and extrude rotating speed 120r/min by carrying out extrusion spheronization after mixture moistening, round as a ball rotating speed 1300r/min, round as a ball time 5min, obtained soft material are dry at 45 DEG C, sieve 4h, must contain pill core
The preparation of isolation coat layer:
1, prepare coating solution: add in the purified water in stirring by isolation coat liquid polyvinyl alcohol 5g, plasticizer benzene dimethyl ester 2g, stir and make it dissolve completely.
2, stir: antitackiness agent Pulvis Talci 0.5g is added homogenizing in purified water, average is complete to add suspension in coating solution prepared by step 1, continues to stir.
3, use fluid bed to carry out hydrojet coating to containing pill core, obtain isolation piller.
The preparation of sustained-release coating layer:
1, sustained release coating liquid is prepared: by Sustained release coating materials triethyl citrate 10g, Sulisi 5g, porogen PEG6000 2g, antitackiness agent Pulvis Talci 5g, gastrointestinal tract adhesive agent gathers carboxy vinyl Doutrate 1g, hydroxypropyl methylcellulose 3g adds in the purified water in stirring, stirring makes it dissolve completely, forms the coating solution of solid content 15%.
2, fluid bed is used to carry out hydrojet coating to isolation piller.
3, coating solution stirring is maintained, the pill core 100 grams that carries obtained above being got by fluid bed sprays coating with carrying out, coating process parameters comprises coating temperature 25 DEG C, atomizing pressure 0.12MPa, and blower frequency is 40Hz, constant flow pump hydrojet speed 0.8 ± 0.1ml/min.Coating solution consumption is 50g, and coating terminates rear taking-up micropill in 40 DEG C of solidification 24h, and take out, obtain amoxicillin slow release micropill, product yield is more than 94%, obtains slow-release micro-pill.
Embodiment 6
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer
Preparation containing pill core:
1, sieve: 40 eye mesh screens crossed by amoxicillin, filler, binding agent and fluidizer
2, mix: accurately take that the amoxicillin 55g, the binding agent that have sieved are methylcellulose 4g, fluidizer is Pulvis Talci 1g, filler is microcrystalline Cellulose 2g, sucrose 20g, dextrin 18g are placed in mixer mix homogeneously
3, sit wetting agent with 75% alcoholic solution and extrude rotating speed 90r/min by carrying out extrusion spheronization after mixture moistening, round as a ball rotating speed 900r/min, round as a ball time 6min, obtained soft material be dry at 45 DEG C, sieve, must pill core be contained
The preparation of isolation coat layer:
1, prepare coating solution: add in the purified water in stirring by isolation coat liquid polyvinyl alcohol 5g, plasticizer benzene dimethyl ester 1g, stir and make it dissolve completely.
2, stir: antitackiness agent Pulvis Talci 1g is added homogenizing in purified water, average is complete to add suspension in coating solution prepared by step 1, continues to stir.
3, use fluid bed to carry out hydrojet coating to containing pill core, obtain isolation piller.
The preparation of sustained-release coating layer:
1, sustained release coating liquid is prepared: by Sustained release coating materials triethyl citrate 15g, Sulisi 5g, porogen PEG6000 1g, lactose 1g, antitackiness agent aluminium stearate 4g, Pulvis Talci 1g, gastrointestinal tract adhesive agent gathers carboxy vinyl Doutrate 2g, hydroxypropyl methylcellulose 3g adds in the purified water in stirring, stirring makes it dissolve completely, forms the coating solution of solid content 15%.
2, fluid bed is used to carry out hydrojet coating to isolation piller.
3, coating solution stirring is maintained, the pill core 100 grams that carries obtained above being got by fluid bed sprays coating with carrying out, coating process parameters comprises coating temperature 25 DEG C, atomizing pressure 0.09MPa, and blower frequency is 40Hz, constant flow pump hydrojet speed 0.8 ± 0.1ml/min.Coating solution consumption is 60g, and coating terminates rear taking-up micropill in 40 DEG C of solidification 24h, and take out, obtain amoxicillin slow release micropill, product yield is more than 95%, obtains slow-release micro-pill.
Embodiment 7
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer
Preparation containing pill core:
1, sieve: 40 eye mesh screens crossed by amoxicillin, filler, binding agent and fluidizer
2, mix: accurately take that the amoxicillin 60g, the binding agent that have sieved are methylcellulose 5g, fluidizer is Pulvis Talci 1g, filler is microcrystalline Cellulose 15g, sucrose 4g, dextrin 15g are placed in mixer mix homogeneously
3, sit wetting agent with 75% alcoholic solution and extrude rotating speed 80r/min by carrying out extrusion spheronization after mixture moistening, round as a ball rotating speed 900r/min, round as a ball time 7min, obtained soft material are dry at 45 DEG C, sieve 3h, must contain pill core
The preparation of isolation coat layer:
1, prepare coating solution: add in the purified water in stirring by isolation coat liquid polyvinyl alcohol 5g, plasticizer benzene dimethyl ester 1g, stir and make it dissolve completely.
2, stir: antitackiness agent Pulvis Talci 1g is added homogenizing in purified water, average is complete to add suspension in coating solution prepared by step 1, continues to stir.
3, use fluid bed to carry out hydrojet coating to containing pill core, obtain isolation piller.
The preparation of sustained-release coating layer:
1, sustained release coating liquid is prepared: by Sustained release coating materials triethyl citrate 5g, Sulisi 10g, porogen PEG6000 1g, sodium chloride 1g, antitackiness agent aluminium stearate 1g, Pulvis Talci 4g, gastrointestinal tract adhesive agent gathers carboxy vinyl Doutrate 2g, hydroxypropyl methylcellulose 2g adds in the purified water in stirring, stirring makes it dissolve completely, forms the coating solution of solid content 10%.
2, fluid bed is used to carry out hydrojet coating to isolation piller.
3, coating solution stirring is maintained, the pill core 100 grams that carries obtained above being got by fluid bed sprays coating with carrying out, coating process parameters comprises coating temperature 25 DEG C, atomizing pressure 0.09MPa, and blower frequency is 40Hz, constant flow pump hydrojet speed 0.9 ± 0.1ml/min.Coating solution consumption is 50g, and coating terminates rear taking-up micropill in 40 DEG C of solidification 24h, and take out, obtain amoxicillin slow release micropill, product yield is more than 95%, obtains slow-release micro-pill.
Embodiment 8
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer
Preparation containing pill core:
1, sieve: 40 eye mesh screens crossed by amoxicillin, filler, binding agent and fluidizer
2, mix: accurately take that the amoxicillin 50g, the binding agent that have sieved are methylcellulose 4g, fluidizer is Pulvis Talci 1g, filler is microcrystalline Cellulose 15g, sucrose 15g, dextrin 15g are placed in mixer mix homogeneously
3, sit wetting agent with 75% alcoholic solution and extrude rotating speed 90r/min by carrying out extrusion spheronization after mixture moistening, round as a ball rotating speed 900r/min, round as a ball time 7min, obtained soft material be dry at 45 DEG C, sieve, must pill core be contained
The preparation of isolation coat layer:
1, prepare coating solution: add in the purified water in stirring by isolation coat liquid polyvinyl alcohol 5g, plasticizer benzene dimethyl ester 1g, stir and make it dissolve completely.
2, stir: antitackiness agent Pulvis Talci 1g is added homogenizing in purified water, average is complete to add suspension in coating solution prepared by step 1, continues to stir.
3, use fluid bed to carry out hydrojet coating to containing pill core, obtain isolation piller.
The preparation of sustained-release coating layer:
1, sustained release coating liquid is prepared: by Sustained release coating materials triethyl citrate 5g, NE30D5g, Sulisi 5g, porogen PEG6000 2g, antitackiness agent Pulvis Talci 5g, gastrointestinal tract adhesive agent gathers carboxy vinyl Doutrate 2g, hydroxypropyl methylcellulose 2g adds in the purified water in stirring, stirring makes it dissolve completely, forms the coating solution of solid content 15%.
2, fluid bed is used to carry out hydrojet coating to isolation piller.
Maintain coating solution stirring, the pill core 100 grams that carries obtained above being got by fluid bed sprays coating with carrying out, coating process parameters comprises coating temperature 25 DEG C, atomizing pressure 0.09MPa, and blower frequency is 40Hz, constant flow pump hydrojet speed 0.9 ± 0.1ml/min.Coating solution consumption is 60g, and coating terminates rear taking-up micropill in 40 DEG C of solidification 24h, and take out, obtain amoxicillin slow release micropill, product yield is more than 97%, obtains slow-release micro-pill.
Although illustrate and describe embodiments of the invention, for the ordinary skill in the art, be appreciated that and can carry out multiple change, amendment, replacement and modification to these embodiments without departing from the principles and spirit of the present invention, scope of the present invention is by claims and equivalents thereof.
Claims (7)
1. an amoxicillin slow release micropill, is characterized in that: described amoxicillin slow release micropill is made up of band pill core, isolation coat layer and sustained-release coating layer from inside to outside; Band pill core is made up of amoxicillin, binding agent, fluidizer and filler, and its concrete percentage by weight is composed as follows:
Amoxicillin 50.0-95.0%
Binding agent 0.5-5.0%
Fluidizer 0.5-5.0%
Filler 4.0-40.0%.
2. amoxicillin slow release micropill as claimed in claim 1, is characterized in that: described binding agent is hydroxypropyl methylcellulose or methylcellulose; Described fluidizer is Pulvis Talci; Described filler is one or more in microcrystalline Cellulose, dextrin, starch, lactose, sucrose, PVP, ethanol, hydroxypropyl emthylcellulose.
3. amoxicillin slow release micropill as claimed in claim 1, it is characterized in that: described isolation coat layer is by isolation coat material, antitackiness agent, plasticizer and solvent composition, its concrete percentage by weight is composed as follows:
Isolation coat material 5.0-10.0%
Antitackiness agent 1.0-10.0%
Plasticizer 0.5-5.0%
Solvent 75.0-90.0%
Wherein, isolation coat material is HPMC or polyvinyl alcohol; Antitackiness agent is Pulvis Talci; Plasticizer is dimethyl phthalate, this dimethyl ester, Polysorbate; Solvent is purified water and/or ethanol.
4. amoxicillin slow release micropill as claimed in claim 1, is characterized in that: described sustained-release coating layer is made up of coating materials, delayed release substrate, gastrointestinal tract adhesive agent, porogen and plasticizer; Its concrete percentage by weight is composed as follows:
Coating materials 55.0-82.7%
Delayed release substrate 15.0-30.0%
Porogen 1.5-6.0%
Gastrointestinal tract adhesive agent 0.3-6.0%
Plasticizer 0.5-5.0%
Wherein, delayed release substrate is ethyl cellulose, polypropylene polysiloxanes; Gastrointestinal tract adhesive agent is one or more in carbomer, methylcellulose, gelatin pectin; Plasticizer is one or more in phthalic acid ester, polrvinyl chloride, Polyethylene Glycol, poly-Pyrusussuriensis fat; Porogen comprises hydrophilic liquid carrier, electrolyte, saccharide, surfactant, macromolecule, microcrystalline Cellulose, hydrophilic gel.
5. amoxicillin slow release micropill as claimed in claim 1, is characterized in that: the weight of sustained-release coating layer is containing pill core 10% ~ 100%.
6. prepare a method for the amoxicillin slow release micropill as described in any one of claim 1-5, it is characterized in that: the concrete steps of described preparation method are as follows:
(1), the preparation of wet feed:
Medicine is mixed homogeneously with fluidizer, filler, adds adhesive, powder is made there is certain plastic moistening uniform material, or wet feed is made wet granular through comminutor;
Extrusion process: be placed in extruder by the plasticity wet feed made or wet grain, the fashion of extrusion such as to roll by wet feed by the hole of tool certain diameter or sieve through screw propulsion or rolling, is squeezed into cylindrical strip extrudate;
(2), round as a ball one-tenth ball process:
Be discharged on the rotation friction plate of spheronizator by above-mentioned extrudate heap, extrudate is then dispersed into the less cylinder that length is equivalent to its diameter, and due to the effect of frictional force, these plastic cylindrical materials ceaselessly roll onboard, are rolled into spheroidal gradually, round as a ball process can distinguish several different stage according to shape of particle, round as a ball one-tenth ball process is by initial short cylindrical shape particle, edge friction plate become under rotary rolling gradually without corner angle is circular cylinder, and then be rolled into dumb-bell shape, oval, until become spherical completely, another becomes ball mechanism, namely time round as a ball after the cylinder forming edge rounding, cylinder bends, reverse, subsequently cylinder break formation two be separated part, the face that both tool one is round and flat, due to the effect of revolving force and frictional force, above-mentioned planar recess, as the cave that same flower is formed, then edge bag stack be rolled into spherical,
(3), the drying of piller:
Extrude the final step that a spheronization prepares piller, drying mode mainly comprises: 1. dry under room temperature, 2. put baking oven inner drying, 3. fluid bed (under evaporating temperature), drying is lyophilization 4., and 5. microwave oven is dry;
The primary structure of micropill is: containing pill core, isolation coat layer, sustained-release coating layer;
Quality containing pill core is the 10.0-95.0% of micropill gross mass;
The quality of isolation coat layer is the 0-10.0% containing pill core;
The quality of sustained-release coating layer is the 10.0-100.0% containing pill core;
Mainly comprise containing pill core component: amoxicillin, adhesive, fluidizer, filler;
Common containing pill core component content: amoxicillin 55.0-95.0%, adhesive 1.5-4.0%, fluidizer 0.5-5%, filler 4.0-40%;
Optimum containing pill core component content: amoxicillin 70.0-90.0%, adhesive 2.5-4.0%, fluidizer 0.9-4.0%, filler 10.0-25.0%;
Isolation coat layer mainly comprises: isolation coat material, antitackiness agent, plasticizer, solvent;
Common isolation coat layer component content: isolation coat material 5.0-10.0%, antitackiness agent 1.5-9.0%, plasticizer 0.5-5%, solvent 75.0-90.0%;
Improve isolation coat layer component content: isolation coat material 5.0-8.0%, antitackiness agent 2.0-6.0%, plasticizer 1.0-5.0%, solvent 82.0-90.0%;
Optimum isolation coat layer component content: isolation coat material 6.0-8.0%, antitackiness agent 3.0-5.0%, plasticizer 2.0-4.0%, solvent 83.0-90.0%;
Sustained-release coating layer mainly comprises: coating materials, delayed release substrate, plasticizer, porogen, gastrointestinal tract adhesive agent;
Common isolation coat layer component content: coating materials 55.0-82.7%, delayed release substrate 15.0-30.0%, plasticizer 0.5-5.0%, porogen 1.5-6.0%, gastrointestinal tract adhesive agent 0.3-6.0%;
Improve isolation coat layer component content: coating materials 60.0-82.7%, delayed release substrate 17.0-25.0%, plasticizer 0.5-5.0%, porogen 1.5-5.0%, gastrointestinal tract adhesive agent 1.0-5.0%;
Optimum isolation coat layer component content: coating materials 70.0-80.0%, delayed release substrate 20.0-25.0%, plasticizer 1.0-3.0%, porogen 2.0-4.0%, gastrointestinal tract adhesive agent 1.0-3.0%.
7. the amoxicillin slow release micropill as described in any one of claim 1-5 is used as the purposes of antibacterials.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510420527.4A CN104983692A (en) | 2015-07-17 | 2015-07-17 | Amoxicillin slow release pellet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510420527.4A CN104983692A (en) | 2015-07-17 | 2015-07-17 | Amoxicillin slow release pellet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104983692A true CN104983692A (en) | 2015-10-21 |
Family
ID=54295686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510420527.4A Pending CN104983692A (en) | 2015-07-17 | 2015-07-17 | Amoxicillin slow release pellet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104983692A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074419A (en) * | 2016-07-28 | 2016-11-09 | 北京万全德众医药生物技术有限公司 | Carbinoxamine slow release oral cavity disintegration tablet and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008101554A1 (en) * | 2007-02-22 | 2008-08-28 | Evonik Röhm Gmbh | Pellets comprising an active substance matrix and a polymer coating, and a method for producing said pellets |
| CN101889984A (en) * | 2009-05-18 | 2010-11-24 | 北京瑞伊人科技发展有限公司 | Amoxicillin enteric-coated formulation composition and preparation method thereof |
| CN101889989A (en) * | 2009-05-18 | 2010-11-24 | 北京瑞伊人科技发展有限公司 | Amoxicillin enteric controlled-release preparation composite and preparation method thereof |
| CN101890006A (en) * | 2009-05-18 | 2010-11-24 | 北京瑞伊人科技发展有限公司 | Amoxicillin sustained-release preparation composition and preparation method thereof |
-
2015
- 2015-07-17 CN CN201510420527.4A patent/CN104983692A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008101554A1 (en) * | 2007-02-22 | 2008-08-28 | Evonik Röhm Gmbh | Pellets comprising an active substance matrix and a polymer coating, and a method for producing said pellets |
| CN101889984A (en) * | 2009-05-18 | 2010-11-24 | 北京瑞伊人科技发展有限公司 | Amoxicillin enteric-coated formulation composition and preparation method thereof |
| CN101889989A (en) * | 2009-05-18 | 2010-11-24 | 北京瑞伊人科技发展有限公司 | Amoxicillin enteric controlled-release preparation composite and preparation method thereof |
| CN101890006A (en) * | 2009-05-18 | 2010-11-24 | 北京瑞伊人科技发展有限公司 | Amoxicillin sustained-release preparation composition and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 张志荣等: "《药剂学》", 31 December 2007, 高等教育出版社 * |
| 王勇等: ""挤出滚圆法制备阿莫西林微丸的处方工艺研究"", 《海峡药学》 * |
| 繆勇等: "《中草药植物提取与深加工新技术实用手册》", 30 April 2004 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074419A (en) * | 2016-07-28 | 2016-11-09 | 北京万全德众医药生物技术有限公司 | Carbinoxamine slow release oral cavity disintegration tablet and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2019284060B2 (en) | Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof | |
| CN102319218B (en) | Drug sustained and controlled release microparticle preparation for treating intestinal diseases, and preparation method thereof | |
| CN1174745C (en) | Use of coating as taste masking agent for oral preparation | |
| US8828429B2 (en) | Release-control composition | |
| CN1178650C (en) | Multiple unit controlled non-independent release pharmaceutical preparations and method for preparing same | |
| CN1134108A (en) | Beads for controlled release and pharmaceutical preparation contg. same | |
| CN101057849A (en) | Slow-releasing preparation containing metformin hydrochloride and glipizide and its preparation method | |
| CN104983718A (en) | Tilmicosin slow release pellet, and preparation method and application thereof | |
| AU2014332024A1 (en) | Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof | |
| CN1931137A (en) | Masked berberine hydrochloride micro pill and its prepn | |
| CN101601663A (en) | Multi-unit sustained-release preparation of levetiracetam and preparation method thereof | |
| CN103054832A (en) | Minocycline hydrochloride sustained-release capsule and preparation method thereof | |
| CN104352441A (en) | DMF (dimethyl fumarate) enteric-coated micropellet and preparation method thereof | |
| CN101590021A (en) | Cefuroxime axetil odor-masking pellet and preparation method | |
| CN101623269A (en) | Oral sustained release granules | |
| EP1677777A1 (en) | Pellets containing venlafaxine hydrochloride | |
| CN104983692A (en) | Amoxicillin slow release pellet and preparation method thereof | |
| JPH05229961A (en) | Spherical particle, its production and medicine using the same | |
| WO2023197579A1 (en) | Sustained-release vitamin c pellet and method for preparing same | |
| CN106619547A (en) | Low-specification meloxicam tablet composition and preparation method thereof | |
| CN102824316A (en) | Esomeprazole medicated pellet and preparing method thereof | |
| UA103781C2 (en) | Novel method for preparing granulates of active principles, and granulates obtained thereof | |
| CN104644565B (en) | A kind of Doxycycline Hyclate pastille piller and preparation method thereof | |
| CN1951385A (en) | Minipills containing simvastatin and derivative thereof and method for preparing formulation thereof | |
| CN103432130B (en) | Ketoprofen lansoprazole sustained-release pellets, as well as preparation method and preparation thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20151021 |