CN104546733A - Benproperine taste-masking pellet - Google Patents
Benproperine taste-masking pellet Download PDFInfo
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- CN104546733A CN104546733A CN201410558241.8A CN201410558241A CN104546733A CN 104546733 A CN104546733 A CN 104546733A CN 201410558241 A CN201410558241 A CN 201410558241A CN 104546733 A CN104546733 A CN 104546733A
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Abstract
The invention provides a taste-masking pellet containing benproperine or pharmaceutically acceptable salt thereof and a preparation method of the taste-masking pellet. The taste-masking pellet contains a medicine layer formed on a blank pellet core, wherein the medicine layer consists of benproperine or pharmaceutically acceptable salt thereof and at least one medicinal excipient mixed with benproperine or the pharmaceutically acceptable salt thereof. Preferably, the taste-masking pellet contains at least one middle isolating layer formed on the medicine layer and at least one taste-masking coating layer. The prepared taste-masking pellet is good in taste-masking effect, and capable of effectively avoiding the bitterness of medicine and tongue-numbing feeling generated during a taking process. The taste-masking pellet can be prepared into a final preparation form according to population taking the medicine and clinical requirements, and the taste-masking pellet, with the good taste-masking effect and multiple available dosage forms, is especially suitable for children. The prepared taste-masking pellet is high in dissolution speed and high in bioavailability.
Description
Invention field
The present invention relates to a kind of oral solid pharmaceutical formulation, comprise benproperine as active constituents of medicine, be specifically related to a kind of odor-masking pellet using benproperine as active component and preparation method thereof.
Technical background
A lot of disease is such as caught a cold, bronchitis, pneumonia and pharyngolaryngitis etc. can cause cough; cough is a kind of protectiveness respiratory reflex of human body action; secretions can be eliminated by cough and get rid of foreign body; often adopt different Therapeutic Method according to different pathogeny, usually use various Chinese patent medicine and chemicals to reach the object for the treatment of at present.
Benproperine is a kind of non-narcotic anti-tussive agents, has dual antitussive effect, lung-vagus reflex that the stretch receptor that mechanism of action mainly blocks lung-pleura produces, and has the inhibitory action to respiratory center concurrently simultaneously.
Benproperine cough medicine dosage form mainly contains tablet (ordinary tablet, dispersible tablet, slow releasing tablet, effervescent tablet), capsule, granule and oral solution dosage form in the market.Although numerous dosage form selection meets and mutually compensate for the demand of adult and children, also there is a common deficiency in these dosage forms, namely mouthfeel is poor.The taste of benproperine own is smelly, bitter in the mouth and take and have certain numb feeling in the tongue, in the process of preparation dosage form especially child's dosage form, how to improve the emphasis that mouthfeel is research.Chinese patent CN03128210 employing adds a large amount of sweeting agents and carrys out taste masking for children taking as Mel etc. is prepared into oral administration solution, and can not reach the effect of taste masking completely, and solution is inconvenient to preserve, preparation process is loaded down with trivial details.The applicant describes and adds correctives and carry out wet granulation and prepare benproperine granule in Chinese patent CN101862298, take after being dissolved in water when taking, although add correctives by interference taste bud, play the flavored action of part, but it can not the abnormal smells from the patient of completely isolated medicine own and numb feeling in the tongue.
Summary of the invention
Term definition
Term herein " comprises " for open language, namely comprises the content specified by the present invention, but does not get rid of otherwise content.
The micropill formed after term " medicine layer micropill " herein refers to drug coated.
Term " sealing coat micropill " herein refers to the micropill wrapping and be isolated layer and formed afterwards.
" weightening finish " is all the weightening finishes relative to the micropill formed in first single stepping herein.
In content above or hereafter, no matter whether use the wording such as " approximately " or " about ", all numerals disclosed at this are approximation.The numerical value of each numeral likely there will be the difference such as 1%, 2%, 5%, 7%, 8%, 10%, 15% or 20%.Whenever disclosing one and having N value digital, any have N+/-1%, N+/-2%, N+/-3%, N+/-5%, N+/-7%, N+/-8%, N+/-10%, and the numeral of N+/-15%or N+/-20% value can be specifically disclosed, and wherein " +/-" refers to and add deduct.Whenever disclosing a lower limit in a numerical range, RL, and a upper limit, RU, time, the numerical value within any scope being in the disclosed can be specifically disclosed.Particularly, contain the following numerical value within the scope of this: R=RL+K* (RU-RL), wherein k be one by 1% increment increase from 1% to 100% variable.As: 1%, 2%, 3%, 4%, 5%...50%, 51%, 52%...95%, 96%, 97%, 98%, 99% or 100%.In addition, also contain especially this disclose above-mentioned with the numerical range of two R definition.
Detailed Description Of The Invention
The applicant is to how effectively covering in the research of benproperine or the strong numb feeling in the tongue of its pharmaceutically acceptable salt, in conjunction with the deficiency of listing dosage form, prepare the odor-masking pellet of a kind of benproperine or its pharmaceutically acceptable salt, it has beyond thought taste masking effect, bitterness and the numb feeling in the tongue of medicine itself can be covered completely, greatly improve the Compliance of patient, and further this odor-masking pellet can be prepared into solid or oral suspension dosage form, adult can be applicable to and can be applicable to children again; The drug form dissolution rate of preparation is fast, and bioavailability is high.
The invention provides a kind of odor-masking pellet containing benproperine or its pharmaceutically acceptable salt, described odor-masking pellet comprises:
A) medicine layer on celphere is formed at, at least one pharmaceutical excipient that this medicine layer contains benproperine or its pharmaceutically acceptable salt and mixes with it;
B) at least one deck taste masking coatings.
In some embodiments, described odor-masking pellet comprises:
A) medicine layer on celphere is formed at, at least one pharmaceutical excipient that this medicine layer contains benproperine or its pharmaceutically acceptable salt and mixes with it;
B) at least one deck is formed at the sealing coat on medicine layer;
C) at least one deck taste masking coatings.
In some embodiments, described odor-masking pellet comprises:
A) medicine layer on celphere is formed at, at least one pharmaceutical excipient that this medicine layer contains benproperine or its pharmaceutically acceptable salt and mixes with it;
B) the ground floor sealing coat on medicine layer is formed at;
C) medicine layer on sealing coat described in being formed at b);
D) second layer sealing coat on the medicine layer described in being formed at c);
The taste masking coatings of the sealing coat described in e) being formed at d).
In some embodiments, described odor-masking pellet comprises:
A) medicine layer on celphere is formed at, at least one pharmaceutical excipient that this medicine layer contains benproperine or its pharmaceutically acceptable salt and mixes with it;
B) sealing coat on medicine layer is formed at;
C) the taste masking coatings on sealing coat described in being formed at b).
In other embodiments, described odor-masking pellet comprises:
A) medicine layer on celphere is formed at, at least one pharmaceutical excipient that this medicine layer contains benproperine or its pharmaceutically acceptable salt and mixes with it;
B) the taste masking coatings on medicine layer described in being formed at a).
Wherein, the salt that described " pharmaceutically acceptable salt " is formed for benproperine and acid, described acid is selected from hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid, phosphoric acid, acetic acid, maleic acid, succinic acid, mandelic acid, fumaric acid, malonic acid, acetone acid, oxalic acid, glycolic and salicylic acid; In some embodiments, described benproperine pharmaceutically acceptable salt is benproperine phosphate.
Described celphere material is selected from one or more of sucrose, lactose, starch and microcrystalline Cellulose; In certain embodiments, described celphere material is selected from sucrose, starch or its combination; In certain embodiments, described celphere material is selected from sucrose.
In certain embodiments, described celphere particle diameter is 180 μm-450 μm.
In described medicine layer, calculate, containing benproperine or its pharmaceutically acceptable salt (in benproperine) 5%-20%, in certain embodiments, containing benproperine or its pharmaceutically acceptable salt 6%-15% based on micropill total weight percent; Also comprise the pharmaceutical excipient that other are suitable, comprise binding agent 0.1%-5%, antiplastering aid 0.1%-10% and surfactant 0.01%-1%.
Described medicine layer, relative to celphere, counts by weight percentage, and increases weight as 20%-70%.
Described binding agent is low viscous macromolecular compound, in certain embodiments, described binding agent be selected from hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose, polyvidone, copolyvidone, methylcellulose, starch, polyvinyl alcohol, sodium carboxymethyl cellulose, sodium alginate one or more; In certain embodiments, binding agent is selected from hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose and polyvidone; In certain embodiments, binding agent is selected from hydroxypropyl methylcellulose (HPMC).
In certain embodiments, hydroxypropyl methylcellulose viscosity is 5-300cp, and viscosity measurement is aqueous solution macromolecular material being mixed with 2% (w/w) concentration, uses Brookfield viscometer determining viscosity at 25 DEG C.
Described antiplastering aid be selected from Pulvis Talci, micropowder silica gel, silicon dioxide, magnesium stearate one or more; In certain embodiments, described antiplastering aid is selected from Pulvis Talci.
Described surfactant be selected from polyoxyethylene sorbitan monoleate, sodium lauryl sulphate, castor oil hydrogenated one or more; In certain embodiments, described surfactant is selected from polyoxyethylene sorbitan monoleate.
Described sealing coat is by binding agent, antiplastering aid and surfactant composition, wherein said binding agent be selected from hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose, polyvidone, copolyvidone, methylcellulose, starch, polyvinyl alcohol, sodium carboxymethyl cellulose, sodium alginate one or more; Described antiplastering aid be selected from Pulvis Talci, micropowder silica gel, silicon dioxide, magnesium stearate one or more; Described surfactant be selected from Polysorbate, sodium lauryl sulphate, hydrogenated castor wet goods one or more.
Described sealing coat, relative to medicine layer micropill, counts by weight percentage, and increases weight as 5%-120%; In certain embodiments, increase weight as 10%-80%; In certain embodiments, increase weight as 20%-60%.
Described taste masking coatings starts when pH is less than or equal to 5 to dissolve, and do not dissolve when pH is greater than 5, described taste masking coatings comprises the macromolecule polymer material being selected from Eudragit E series; The weight of the taste masking coatings in above-mentioned micropill, relative to sealing coat micropill, counts by weight percentage, and increases weight as 10%-80%; In certain embodiments, increase weight as 10%-75%; In certain embodiments, increase weight as 15%-75%.
An odor-masking pellet for benproperine or its pharmaceutically acceptable salt, finally according to medication crowd and clinical demand, can make final dosage form by the odor-masking pellet of preparation further.In certain embodiments, be packed into gelatine capsule and be prepared into capsule, in certain embodiments, be pressed into tablet with suitable tablet excipient, be prepared into dry suspension with suitable adjuvant in certain embodiments.
Present invention also offers a kind of method of odor-masking pellet containing preparing benproperine or its pharmaceutically acceptable salt, comprising step:
1) by benproperine or its pharmaceutically acceptable salt, binding agent, antiplastering aid and surfactant-dispersed in suitable solvent, be mixed with medicine layer coating solution, celphere is placed in fluid bed, spray nitride layer coating solution carries out coating;
2) by taste masking coating material, antiplastering aid and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, in fluid bed spraying carry out coating.
In some embodiment schemes, the described method preparing odor-masking pellet, also comprises step: by binding agent, antiplastering aid and surfactant-dispersed in coating solvent, is mixed with sealing coat coating solution, and in fluid bed, coating is carried out in spraying.
The invention provides odor-masking pellet of a kind of benproperine or its pharmaceutically acceptable salt and preparation method thereof.The odor-masking pellet of preparation has excellent taste masking effect, effectively can avoid the bitterness of medicine itself and take the numb feeling in the tongue produced in process.Described odor-masking pellet according to medication crowd and clinical demand, can be prepared into final dosage form, and good taste masking effect and selectable multi-pharmaceutics are particularly useful for children.The odor-masking pellet dissolution rate of preparation is fast, and bioavailability is high.
Specific embodiment mode
The invention discloses odor-masking pellet of a kind of benproperine or its pharmaceutically acceptable salt and preparation method thereof.By the following examples the present invention is described in detail, but does not limit the present invention.
In the specific embodiment of the invention, celphere is bought from Gaocheng Biologic Nutrition Technology Co Ltd, Hangzhou, and commodity are called medicinal fine pellet core; Hydroxypropyl methylcellulose is bought from DOW Chemical; Pulvis Talci is bought from the magnificent company limited of LONGSHENG IN GUANGXI; Polyoxyethylene sorbitan monoleate and sodium lauryl sulphate are purchased and are all bought from Hu'nan Erkang Pharmaceutical Co., Ltd.; Silicon dioxide and methacrylic acid aminoalkyl ester copolymer are all bought from EVONIK; Magnesium stearate is bought from PETER GREVEN.
Embodiment 1: prepared by medicine layer micropill
Celphere is placed in fluid bed, gets the waterborne suspension of benproperine phosphate, HPMC, Pulvis Talci and polyoxyethylene sorbitan monoleate preparation, end spray coating, drying obtains medicine layer micropill.
| Composition | Unit recipe quantity (mg) |
| Celphere | 50 |
| Benproperine phosphate | 15 |
| HPMC(E5-LV) | 6 |
| Pulvis Talci | 3 |
| Polyoxyethylene sorbitan monoleate | 1 |
Embodiment 2: prepared by medicine layer micropill
Celphere is placed in fluid bed, gets the waterborne suspension of benproperine phosphate, HPMC, Pulvis Talci and polyoxyethylene sorbitan monoleate preparation, end spray coating, drying obtains medicine layer micropill.
| Composition | Unit recipe quantity (mg) |
| Celphere | 150 |
| Benproperine phosphate | 45 |
| HPMC(E5-LV) | 18 |
| Pulvis Talci | 9 |
| Polyoxyethylene sorbitan monoleate | 3 |
Embodiment 3: prepared by medicine layer micropill
Celphere is placed in fluid bed, gets the waterborne suspension of benproperine phosphate, HPMC, Pulvis Talci and polyoxyethylene sorbitan monoleate preparation, end spray coating, drying obtains medicine layer micropill.
| Composition | Unit recipe quantity (mg) |
| Celphere | 100 |
| Benproperine phosphate | 30 |
| HPMC(E5-LV) | 12 |
| Pulvis Talci | 6 |
| Polyoxyethylene sorbitan monoleate | 2 |
Embodiment 4: prepared by sealing coat micropill
Be scattered in coating solvent by HPMC, silicon dioxide and magnesium stearate, be mixed with sealing coat coating solution, add embodiment 1,2 in fluid bed, the medicine layer micropill that in 3, any one is prepared, sealing coat coating solution of spraying in fluid bed prepares sealing coat micropill.
| Composition | Unit recipe quantity (mg) |
| HPMC(E5-LV) | 5 |
| Silicon dioxide (A200) | 2.25 |
| Magnesium stearate | 0.25 |
Embodiment 5: prepared by sealing coat micropill
Be scattered in coating solvent by HPMC, silicon dioxide and magnesium stearate, be mixed with sealing coat coating solution, add embodiment 1,2, the medicine layer micropill that in 3, any one is prepared, sealing coat coating solution of spraying in fluid bed prepares sealing coat micropill.
| Composition | Unit recipe quantity (mg) |
| HPMC(E5-LV) | 120 |
| Silicon dioxide A200 | 54 |
| Magnesium stearate | 6 |
Embodiment 6: prepared by sealing coat micropill
Be scattered in coating solvent by HPMC, silicon dioxide and magnesium stearate, be mixed with sealing coat coating solution, add the medicine layer micropill of preparation in embodiment 3, sealing coat coating solution of spraying in fluid bed prepares sealing coat micropill.
| Composition | Unit recipe quantity (mg) |
| HPMC(E5-LV) | 60 |
| Silicon dioxide (A200) | 27 |
| Magnesium stearate | 3 |
Embodiment 7: prepared by odor-masking pellet
By methacrylic acid aminoalkyl ester copolymer E type, antiplastering aid and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, add the sealing coat micropill of preparation in embodiment 6 in fluid bed, taste mask layer of spraying in fluid bed coating solution prepares odor-masking pellet.
| Composition | Unit recipe quantity (mg) |
| Methacrylic acid aminoalkyl ester copolymer E type | 5 |
| Pulvis Talci | 6.73 |
| Sodium lauryl sulphate | 0.27 |
Embodiment 8: prepared by odor-masking pellet
By methacrylic acid aminoalkyl ester copolymer E type, antiplastering aid and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, add the sealing coat micropill of preparation in embodiment 6 in fluid bed, taste mask layer of spraying in fluid bed coating solution prepares odor-masking pellet.
| Composition | Unit recipe quantity (mg) |
| Methacrylic acid aminoalkyl ester copolymer E type | 10 |
| Pulvis Talci | 13.46 |
| Sodium lauryl sulphate | 0.54 |
Embodiment 9: prepared by odor-masking pellet
By methacrylic acid aminoalkyl ester copolymer E type, lubricant and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, add the sealing coat micropill of preparation in embodiment 6 in fluid bed, taste mask layer of spraying in fluid bed coating solution prepares odor-masking pellet.
| Composition | Unit recipe quantity (mg) |
| Methacrylic acid aminoalkyl ester copolymer E type | 15 |
| Pulvis Talci | 20.19 |
| Sodium lauryl sulphate | 0.81 |
Embodiment 10: prepared by odor-masking pellet
By methacrylic acid aminoalkyl ester copolymer E type, lubricant and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, add the sealing coat micropill of preparation in embodiment 6 in fluid bed, taste mask layer of spraying in fluid bed coating solution prepares odor-masking pellet.
| Composition | Unit recipe quantity (mg) |
| Methacrylic acid aminoalkyl ester copolymer E type | 20.00 |
| Pulvis Talci | 26.92 |
| Sodium lauryl sulphate | 1.08 |
Embodiment 11: prepared by odor-masking pellet
By methacrylic acid aminoalkyl ester copolymer E type, lubricant and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, add the sealing coat micropill of preparation in embodiment 6 in fluid bed, taste mask layer of spraying in fluid bed coating solution prepares odor-masking pellet.
| Composition | Unit recipe quantity (mg) |
| Methacrylic acid aminoalkyl ester copolymer E type | 40 |
| Pulvis Talci | 53.84 |
| Sodium lauryl sulphate | 2.16 |
Embodiment 12: prepared by odor-masking pellet
By methacrylic acid aminoalkyl ester copolymer E type, lubricant and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, add the sealing coat micropill of preparation in embodiment 6 in fluid bed, taste mask layer of spraying in fluid bed coating solution prepares odor-masking pellet.
| Composition | Unit recipe quantity (mg) |
| Methacrylic acid aminoalkyl ester copolymer E type | 60 |
| Pulvis Talci | 90.49 |
| Sodium lauryl sulphate | 5.24 |
Embodiment 13: prepared by odor-masking pellet
By methacrylic acid aminoalkyl ester copolymer E type, lubricant and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, add the sealing coat micropill of preparation in embodiment 6 in fluid bed, taste mask layer of spraying in fluid bed coating solution prepares odor-masking pellet.
| Composition | Unit recipe quantity (mg) |
| Methacrylic acid aminoalkyl ester copolymer E type | 75 |
| Pulvis Talci | 100.95 |
| Sodium lauryl sulphate | 4.05 |
Embodiment 14: prepared by odor-masking pellet
By methacrylic acid aminoalkyl ester copolymer E type, lubricant and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, add the sealing coat micropill of preparation in embodiment 6 in fluid bed, taste mask layer of spraying in fluid bed coating solution prepares odor-masking pellet.
| Composition | Unit recipe quantity (mg) |
| Methacrylic acid aminoalkyl ester copolymer E type | 80 |
| Pulvis Talci | 107.68 |
| Sodium lauryl sulphate | 4.32 |
Embodiment 15: prepared by multilayer medicine layer odor-masking pellet
Celphere is placed in fluid bed, gets the waterborne suspension of benproperine phosphate, HPMC, Pulvis Talci and polyoxyethylene sorbitan monoleate preparation, end spray coating, drying obtains medicine layer micropill; Be scattered in coating solvent by HPMC, silicon dioxide and magnesium stearate, be mixed with sealing coat coating solution, by the medicine layer micropill of preparation, sealing coat coating solution of spraying in fluid bed prepares ground floor sealing coat micropill; Repeat aforementioned medicine accommodation layer step, obtain second layer medicine layer micropill; Repeat aforementioned sealing coat step, obtain second layer sealing coat micropill; By methacrylic acid aminoalkyl ester copolymer E type, lubricant and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, add the sealing coat micropill of preparation in fluid bed, taste mask layer of spraying in fluid bed coating solution prepares odor-masking pellet.
Embodiment 16: In Vitro Dissolution
In Vitro Dissolution laboratory reference " Chinese Pharmacopoeia version in 2010 " annex XC method, the odor-masking pellet of preparation in embodiment 7, embodiment 8, embodiment 9, embodiment 10, embodiment 11, embodiment 12, embodiment 13 and embodiment 14 is placed in 0.1M HCl medium and carries out In Vitro Dissolution test, odor-masking pellet dissolution rate is under one's belt investigated in simulation, and then investigates bioavailability.Result is as shown in table 1.
Table 1 benproperine phosphate odor-masking pellet stripping result (0.1M HCL, 900mL, slurry processes, 50RPM) in 15min in 0.1M HCl
| Embodiment | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 |
| Taste masking coatings weightening finish (%) | 5 | 10 | 15 | 20 | 40 | 60 | 75 | 80 |
| 15min stripping (%) | 99.9 | 99.2 | 98.5 | 96.3 | 97.0 | 94.2 | 85.2 | 83.8 |
Table 1 shows odor-masking pellet 15min stripping result in 0.1M HCL, has dissolution rate fast, do not affect the bioavailability of medicine during weightening finish 5%-75%; When taste mask layer weightening finish is greater than 80%, taste masked particle 15min dissolution in 0.1M HCL is less than 85%, can not meet 15min and be greater than 85% requirement discharged fast, likely affect bioavailability in body.
Embodiment 17: sensory test
The odor-masking pellet taking preparation in appropriate embodiment 7, embodiment 8, embodiment 9, embodiment 10, embodiment 11, embodiment 12, embodiment 13 and embodiment 14 is placed in beaker in right amount, add water and stir 2min, after leaving standstill 15min and 30min, test numb feeling in the tongue respectively.Result is as shown in table 2.
Table 2 benproperine phosphate odor-masking pellet sensory test result
Test display in table 2, leave standstill in 15min, the odor-masking pellet of 5% weightening finish has stronger numb feeling in the tongue, the odor-masking pellet of 10% weightening finish is substantially without numb feeling in the tongue, individual subject has slight numb feeling in the tongue and feels, along with coating weight gain is from the progressively increase of 10% to 80%, does not occur numb feeling in the tongue, show good taste masking effect, and taste masking effect is constant in numb feeling in the tongue after taste masking weightening finish is more than 40%.Leave standstill in 30min, taste masking effect is substantially identical with in 15min, and wherein 5% weightening finish odor-masking pellet has strong numb feeling in the tongue, during weightening finish 10%-80%, does not occur numb feeling in the tongue, has good taste masking effect.
In addition, leave standstill stripping and the display of sensory test result of 15min in table 2, when odor-masking pellet stirs 2 minutes in water, when standing 15min stripping is less than 30%, taste masking effect may persist to 30min, thus reaches the effect of the effective taste masking of oral administration process.
Comprehensive dissolution rate in vitro and sensory test are tested known, and when the weightening finish of taste masking coatings is within the scope of 10%-75%, it both can meet bioavailability requirement, also can meet mouthfeel requirement.
Those skilled in the art can use for reference present disclosure, and suitable replacing ratio or consumption or pharmaceutic adjuvant are achieved.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, such as, to rationally delete in odor-masking pellet or increase sealing coat or medicine layer or the coatings number of plies, and the mode of each layer being carried out reasonable combination and alternate combinations be all deemed to be included in the present invention.Method of the present invention is described by preferred embodiment, related personnel obviously can not depart from content of the present invention, spirit and scope method as herein described is changed or suitably change with combination, realize and apply the technology of the present invention.
Claims (16)
1. one kind contains the odor-masking pellet of benproperine or its pharmaceutically acceptable salt, described odor-masking pellet comprises: be formed at the medicine layer on celphere, at least one pharmaceutical excipient that this medicine layer contains benproperine or its pharmaceutically acceptable salt and mixes with it; At least one deck taste masking coatings.
2. odor-masking pellet according to claim 1, described odor-masking pellet also comprises: at least one deck is formed at the intermediate isolating layer on medicine layer.
3. odor-masking pellet according to claim 2, described odor-masking pellet comprises:
A) medicine layer on celphere is formed at, at least one pharmaceutical excipient that this medicine layer contains benproperine or its pharmaceutically acceptable salt and mixes with it;
B) sealing coat on medicine layer is formed at;
C) the taste masking coatings on sealing coat described in being formed at b).
4. odor-masking pellet according to claim 2, described odor-masking pellet comprises:
A) medicine layer on celphere is formed at, at least one pharmaceutical excipient that this medicine layer contains benproperine or its pharmaceutically acceptable salt and mixes with it;
B) the ground floor sealing coat on medicine layer is formed at;
C) medicine layer on sealing coat described in being formed at b);
D) second layer sealing coat on the medicine layer described in being formed at c);
The taste masking coatings of the sealing coat described in e) being formed at d).
5. odor-masking pellet according to claim 1, described odor-masking pellet comprises:
A) medicine layer on celphere is formed at, at least one pharmaceutical excipient that this medicine layer contains benproperine or its pharmaceutically acceptable salt and mixes with it;
B) the taste masking coatings on medicine layer described in being formed at a).
6., according to the arbitrary described odor-masking pellet of claim 1-5, described pharmaceutically acceptable salt is phosphate.
7., according to the arbitrary described odor-masking pellet of claim 1-5, described taste masking coatings comprises the macromolecule polymer material being selected from Eudragit E series.
8. odor-masking pellet according to claim 7, described taste masking coatings starts when pH is less than or equal to 5 to dissolve, and does not dissolve when pH is greater than 5.
9., according to the arbitrary described odor-masking pellet of claim 1-5, described taste masking coatings, relative to sealing coat micropill, counts by weight percentage, weightening finish 10% ~ 80%; Or 10% ~ 75%; Or 15% ~ 75%.
10., according to the arbitrary described odor-masking pellet of claim 1-5, described celphere material is selected from one or more of sucrose, lactose, starch and microcrystalline Cellulose.
11. according to the arbitrary described odor-masking pellet of claim 1-5, described medicine layer calculates based on micropill total weight percent, containing benproperine or its pharmaceutically acceptable salt 5% ~ 20%, binding agent 0.1% ~ 5%, antiplastering aid 0.1% ~ 10% and surfactant 0.01% ~ 1%.
12. odor-masking pellets according to claim 11, described binding agent be selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvidone, copolyvidone, methylcellulose, starch, polyvinyl alcohol, sodium carboxymethyl cellulose, sodium alginate one or more; Described antiplastering aid be selected from Pulvis Talci, micropowder silica gel, silicon dioxide, magnesium stearate one or more; Described surfactant be selected from polyoxyethylene sorbitan monoleate, sodium lauryl sulphate, castor oil hydrogenated one or more.
13. according to the arbitrary described odor-masking pellet of claim 2-4, and wherein sealing coat is relative to medicine layer micropill, counts by weight percentage, and increases weight as 5%-120%; Or 10%-80%; Or 20%-60%.
14. according to the arbitrary described odor-masking pellet of claim 2-4, wherein sealing coat comprises binding agent, antiplastering aid and surfactant, wherein said binding agent be selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvidone, copolyvidone, methylcellulose, starch, polyvinyl alcohol, sodium carboxymethyl cellulose, sodium alginate one or more; Described antiplastering aid be selected from Pulvis Talci, micropowder silica gel, silicon dioxide, magnesium stearate one or more; Described surfactant be selected from polyoxyethylene sorbitan monoleate, sodium lauryl sulphate, castor oil hydrogenated one or more.
Prepare the described method containing the odor-masking pellet of benproperine or its pharmaceutically acceptable salt as arbitrary in power 1-5, comprise for 15. 1 kinds:
1) by benproperine or its pharmaceutically acceptable salt, binding agent, antiplastering aid and surfactant-dispersed in suitable solvent, be mixed with medicine layer coating solution, celphere is placed in fluid bed, spray nitride layer coating solution carries out coating;
2) by taste masking coating material, antiplastering aid and surfactant-dispersed in coating solvent, be mixed with taste masking coating solution, in fluid bed spraying carry out coating.
16. methods according to claim 15, also comprise:
By binding agent, antiplastering aid and surfactant-dispersed in coating solvent, be mixed with sealing coat coating solution, in fluid bed, coating is carried out in spraying.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104784122A (en) * | 2014-01-20 | 2015-07-22 | 广东东阳光药业有限公司 | Benproperine-contained solid preparation |
| CN105943519A (en) * | 2016-06-22 | 2016-09-21 | 福建省微生物研究所 | Bepotastine besilate taste masking granules |
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| CN105943519A (en) * | 2016-06-22 | 2016-09-21 | 福建省微生物研究所 | Bepotastine besilate taste masking granules |
Also Published As
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| CN104546733B (en) | 2019-04-19 |
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