CN1946376A - Coated tablet composition and method of manufacturing the same - Google Patents
Coated tablet composition and method of manufacturing the same Download PDFInfo
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- CN1946376A CN1946376A CN200580012622.5A CN200580012622A CN1946376A CN 1946376 A CN1946376 A CN 1946376A CN 200580012622 A CN200580012622 A CN 200580012622A CN 1946376 A CN1946376 A CN 1946376A
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Abstract
A coated tablet formulation is provided which includes a medicament such as the PPAR / dual agonist peliglitazar or muraglitazar. The coated tablet includes a tablet core containing one or more fillers, one or more binders, one or more disintegrants, and other conventional excipients, and a coating on the tablet core, which coating may include one or more layers, at least one layer of which is formed of medicament and one or more coating polymers, preferably a hydroxypropylmethyl cellulose based polymer. A method for forming the coated tablet via a spray-dried coating technique is also provided.
Description
The application advocates the U.S. Provisional Application No.60/556 that on March 25th, 2004 submitted to, the No.60/648 that on February 1st, 331 and 2005 submitted to, and 872 priority, it is for reference that its full content is incorporated this paper into.
Technical field
The present invention relates to a kind of coated tablet composition, it comprises that coating has for example tablet core of PPAR α/γ antagonist of medicament, also relates to the preparation method of described coated tablet composition.
Background technology
PPAR α/γ dual antagonist (being commonly referred to peliglitazar (peliglitazar)) with following array structure is disclosed in U.S. Patent No. 6,414, in 002, it can reduce glucose and lipid level, and therefore can be used for treating type ii diabetes and dyslipidemia (dyslipidemia), have been found that this chemical compound is via following reaction generation base catalysis degraded as follows and acid catalysis degraded.
The base catalysis degraded of compd A
The acid catalysis degraded of compd A
For fear of the base catalysis degraded, advised the citric acid adding is contained in the capsule composition of PPAR α/γ dual antagonist.But, find to add the degradation product that citric acid can't avoid forming base catalysis fully.And, acid catalyzed degradation product is also arranged.Even under the general condition of storage of 25 ℃/60% relative humidity, Degradation Level also is unacceptable.Can only prevent the formation of the degradation product of capsule composition via the cold preservation capsule.
In order to prevent the resolution problem relevant with capsule composition, tablet formulation is become dry or moist granulating composite, do not add for example citric acid of any pH modifier.Find that drying or moist granulating composite manifest the stability that is better than capsule composition, and moist granule tablet shows the stability that is better than the dried particles tablet.Even without citric acid, the dried particles tablet continues to manifest and has an acid catalyzed degradation product.Moist granule tablet manifests gratifying stability under 30 ℃/60% relative humidity, but under the acceleration environment of 40 ℃/75% relative humidity (opening) and 50 ℃ of conditions, renders a service the significantly increase that (potency) loss is accompanied by palliating degradation degree.
In view of the above, find out that significant need comprises the stable pharmaceutical composition of following medicament, described medicament generation base catalysis degraded and acid catalysis degraded.
PPAR α/γ dual antagonist Pargluva (muraglitazar) with following array structure also is disclosed in U.S. Patent No. 6,414, in 002.
Summary of the invention
According to the present invention, a kind of coated tablet is provided, it can comprise the medicament that base catalysis degraded and/or acid catalysis degraded take place, but this medicament is stable unusually under the normal storage condition of 30 ℃ and 60% relative humidity.
Coated tablet of the present invention comprises tablet core and coating at least one coatings on tablet core, and this coatings is by medicament and at least a coating polymer formation.This pharmacy optimization is a U.S. Patent No. 6,414, and 002 contains or disclosed chemical compound, comprises following PPAR α/γ dual antagonist (being also referred to as compd A or peliglitazar)
And following PPAR α/γ dual antagonist (being also referred to as compd B or Pargluva).
In a preferred embodiment, coated tablet of the present invention comprises a) tablet core, it is by one or more extenders or filler, one or more optional binding agents, one or more optional disintegrating agents and optional one or more tabletting lubricants (tableting lubricant) and one or more medicaments of choosing wantonly form, and b) at least one coatings, it comprises one or more medicaments and coating polymer, described coating polymer is the hydroxypropyl emthylcellulose polymer preferably, and this coatings preferably is coated on the tablet core by spraying and is applied on the tablet core.
This tablet core can not contain medicament maybe can comprise any medicament that can be used in combination with the medicament in the coatings.Medicament in coatings also can use in tablet core, but this is not preferred.
In preferred embodiment of the present invention, protective layer is gone up and be used as to the second coatings coating in initial coatings (containing medicament).Except not containing medicament, the composition preferred class of second coatings is similar to initial coatings.But second coatings also can be by other coating polymer formation.
This coatings preferably applies via the spraying coating technique.
Have been found that with the conventional tablet of using conventional dry type granulation or wet granulation technology to produce and compare that coated tablet of the present invention has excellent chemical stability.Have five to six unit operationss relatively with using the conventional tablet manufacture method, the spray coating method only relates to a unit operations relevant with medicament.This point particular importance when medicament needs special handling, and therefore whole unit operations must carry out in sealing area (containment area).And less unit operations will reduce cycle time.When use needs the medicament of special handling,, must avoid contacting this medicament with the protection medical personnel by this tablet of coating even when using conventional method production to contain the tablet of this medicament.Also necessary this tablet of coating is to prevent photodissociation degraded (photolytic degradation) or prevent that medicament from hydrolysis taking place when dampness exists.
By using other medicament tablet to be applied to described other medicament tablet as the spray coating layer that tablet core (rather than placebo tablet nuclear (tablet placebocore)) also will contain described medicament and coating polymer, the spray coating method also will help preparing the compositions of described medicament and another kind of medicament.
Coated tablet of the present invention can use disc type coating machine or liquid bed coating machine.
In addition, according to the present invention, a kind of method that is used to prepare coated tablet of the present invention is provided, and this method may further comprise the steps: tablet core is provided and uses at least a this tablet core of coatings compositions coating, and the tablet of dry this coating and form coated tablet of the present invention.This coatings compositions comprises medicament and at least a coating polymer and coating solvent.
In the preferred implementation of the inventive method, this coatings compositions is that the form with the suspension of coating polymer applies.
Second coatings is to be applied to above exsiccant first coatings with suspension, and second coatings does not need to contain medicament (though time yet can) if desired, and can be formed by other compositions of first coatings.
When preparation coated tablet of the present invention, preparation medicament and the coating suspension of coating polymer in water.Operable other coating solvent comprises ethanol, methanol and isopropyl alcohol, preferred water.Tablet core (it does not preferably contain medicament, and medicament is present in the coatings) is the above-mentioned suspension coating of with medicament and coating polymer.With the tablet drying of coating like this, to prepare coated tablet of the present invention.
When coated tablet of the present invention comprises an outer protection layer, as the situation of the initial coating suspension of preparation, preparation coating suspension, but do not make with medicament.As description, the coating suspension is coated on the tablet of previous coating then, forms the protectiveness coatings thereon at initial coating.
Coated tablet of the present invention can be treated mammal for example type ii diabetes and the dyslipidemia of people, Canis familiaris L. and cat.
The specific embodiment
The tablet core that uses at coated tablet of the present invention comprises conventional drug excipient, thereby form pharmaceutically acceptable solid tablet nuclear, also comprise optional medicament, the form of this tablet core can be sheet, pearl, globule (beadlet) or pill, and above-mentioned form of ownership is generically and collectively referred to as tablet core.
Coated tablet of the present invention comprises medicament, preferred U.S. Patent No. 6,414,002 disclosed PPAR α/γ dual antagonist, for example compd A and compd B, its amount be final tablet about 0.1% to about 70% weight, preferred about 0.25% to about 25% weight, or about 0.1 to about 200 milligrams, preferred about 0.1 to about 50 milligrams, more preferably from about 0.1 to about 25 milligrams.
The tablet core that uses at coated tablet of the present invention preferably contains:
A) at least a extender or filler;
B) preferably but randomly, at least a binding agent;
C) preferably but randomly, at least a disintegrating agent;
D) preferably but randomly, at least a lubricant; And
E) randomly, at least a medicament;
Wherein
A) amount of extender or filler is about 1 to about 95% weight, is preferably about 10 to about 85% weight;
B) the optional amount of binding agent is about 0 to about 20% weight, is preferably about 1 to about 10% weight;
C) the optional amount of disintegrating agent is about 0 to about 20% weight, is preferably about 0.25 to about 15% weight;
D) the optional amount of lubricant is about 0 to about 5% weight, is preferably about 0.2 to about 2% weight;
E) Ren Xuan medicament exists with therapeutic dose, and this amount depends on the character of medicament and/or disclosed as PDR (Physician ' s Desk Reference).
Should extender be microcrystalline Cellulose and/or lactose monohydrate;
Disintegrating agent is cross-linking sodium carboxymethyl cellulose (croscarmellose sodium); And lubricant is a magnesium stearate.
The tablet core that is present in the coated tablet of the present invention can prepare in proper order via the interpolation of several different methods and excipient.The purposes of these compositionss is not limited to particular dosage form or production method.Tablet core can be via wet granulation, dry granulation, directly blend or any other pharmaceutically acceptable method production.
According to the present invention, a kind of method for optimizing that is used for preparing the tablet core that is used in coated tablet of the present invention is provided, it may further comprise the steps: one or more excipient of blend are extender, disintegrating agent and lubricant for example, and blend is pressed into tablet.Thereby preferably lubricant is added into and is convenient to tablet press in the blend.
Extender or the filler amount in tablet composition of the present invention be compositions about 1 to about 95% weight, preferred about 10 to about 85% weight.Be suitably in the extender that uses in the coated tablet of the present invention or the example of filler and include but not limited to cellulose derivative for example microcrystalline Cellulose or lignose, lactose, sucrose, starch, pregelatinized starch, glucose, mannitol, fructose, xylitol, Sorbitol, corn starch, modified corn starch, inorganic salts is calcium carbonate for example, calcium phosphate, dicalcium phosphate, calcium sulfate, dextrin/dextrates, maltodextrin, compressible saccharide and other known extender or filler, and/or above-mentioned two or more mixture, preferably microcrystalline cellulose.
Optional about 0 amount to about 20% weight with compositions of binding agent is present in the pharmaceutical composition of the present invention, preferably exists with about 1 amount to about 10% weight.The example that is suitably in the binding agent that uses in the pharmaceutical composition of the present invention includes but not limited to: hydroxypropyl cellulose, corn starch, pregelatinized starch, modified corn starch, (molecular weight is about 5 to polyvinyl pyrrolidone (PVP), 000 to about 1,000,000, preferred about 40,000), hydroxypropyl emthylcellulose (HPMC), lactose, arabic gum, ethyl cellulose, cellulose acetate, and wax binding agent (wax binder), Brazil wax for example, paraffin, spermaceti, polyethylene or crystallite shape wax, and other conventional binding agent, and/or above-mentioned two or more mixture, preferred hydroxypropyl cellulose.
Optional about 0 amount to about 20% weight with compositions of disintegrating agent is present in the pharmaceutical composition of the present invention, preferably exists with about 0.25 amount to about 15% weight.The example that is suitably in the disintegrating agent that uses in this pharmaceutical composition includes but not limited to: cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone (crospovidone), starch, potato starch, pregelatinized starch, corn starch, primojel, microcrystalline Cellulose, low hydroxypropyl cellulose or other known disintegrating agents that replaces, preferred cross-linking sodium carboxymethyl cellulose.
Lubricant the best is present in the pharmaceutical composition of the present invention with about 0.1 amount to about 5% weight, preferably exists with about 0.2 amount to about 2% weight.The example that is suitably in the tabletting lubricant that uses in the pharmaceutical composition of the present invention includes but not limited to: magnesium stearate, zinc stearate, calcium stearate, Talcum, Brazil wax, stearic acid, Palmic acid, sodium stearyl fumarate or hydrogenant vegetable oil and fat, or other known tabletting lubricant, and/or above-mentioned two or more mixture, preferred magnesium stearate.
Can prepare coatings compositions (being also referred to as first coatings) as mentioned above, it comprises medicament, coatings polymer, for example hydroxypropyl emthylcellulose, polyvinyl acetate, polyvinyl alcohol, ethyl cellulose, methacrylic acid (ester) base polymer or hydroxypropyl cellulose, preferred hydroxypropyl emthylcellulose or polyvinyl alcohol.Coatings also can comprise plasticizer for example acetin, diethyl phthalate, decanedioic acid tributyl or Polyethylene Glycol, preferred acetin; And caking inhibiter or fluidizer for example titanium dioxide, fumed silica or magnesium stearate of Talcum or opacifier for example, preferred titanium dioxide.
The composition of second coatings can be similar to first coatings, but it does not preferably contain medicament, and does not have medicament at least in the first coatings.
First coatings is formed by following component: account for about 10 to about 95% of this coatings, suitable about 30 coating polymer to about 88% weight, account for about 5 to about 90% of this coatings, suitable about 14 medicaments to about 70% weight, account for about 5 to about 30% of this coatings, than suitable about 8 optional plasticizers to about 9% weight, account for about 20 to about 40% of this coatings, suitable about 30 opacifiers to about 35% weight, and account for 0.1 to 3% of this coatings, optional colorant than suitable 0.5 to 2%, for example red iron oxide, yellow iron oxide, or the combination of red iron oxide and yellow iron oxide.
Tablet composition according to preferable coating of the present invention is as follows.
| The material tablet core | Possible range accounts for the weight %/milligram (for 200 milligrams of tablet cores) of tablet core | Preferred range weight %/milligram (for 200 milligrams of tablet cores) |
| Extender | 2 to 95%/4 to 190 milligrams | 10 to 85%/20 to 170 milligrams |
| Lactose | 0 to 95%/0 to 190 milligrams | 20 to 75%/40 to 150 milligrams |
| Microcrystalline Cellulose | 0 to 95%/0 to 190 milligrams | 20 to 75%/40 to 150 milligrams |
| Disintegrating agent | 0 to 20%/0 to 40 milligrams | 0.25 to 15%/0.5 to 30 milligram |
| Cross-linking sodium carboxymethyl cellulose | 1 to 20%/0.5 to 40 milligrams | 2 to 10%/4 to 20 milligrams |
| Lubricant | 0.1 to 4%/0 to 8 milligram | 0.2 to 2%/0.4 to 4 milligram |
| Magnesium stearate | 0.1 to 4%/0.2 to 8 milligram | 0.2 to 2%/0.4 to 4 milligram |
| The first film coatings | Account for the weight %/milligram (not considering the weight of tablet core) of film coating layer | The weight % of film coating layer/milligram (not considering the weight of tablet core) |
| Medicament | ||
| PPAR α/γ dual antagonist | 5 to 90%/0.1 to 200 milligrams | 14 to 67%/0.2 to 50 milligrams |
| Coating polymer and optional plasticizer, fluidizer and coloring agent | 10 to 95%/15 to 190 milligrams | 30 to 88%/3 to 100 milligrams |
| The second film coating layer | Account for the weight %/milligram of the second film coating layer | Account for the weight %/milligram (not considering the weight of placebo tablet) of film coating layer |
| Coating polymer, and optional fluidizer and coloring agent | 100%/1 to 25 milligram | 100%/2 to 15 milligram |
The following example is represented preferred implementation of the present invention.
Embodiment
Embodiment 1
Being prepared as follows coating on it has the tablet of 0.5 milligram, 1 milligram, 2 milligrams, 4 milligrams, 8 milligrams and 10 milligrams coating of PPAR α/γ dual antagonist compd A (peliglitazar).
Be prepared as follows the film-coated tablet core that is used for following composition.
Table 1
The composition that is used for film-coated tablet core
| Composition | Content, milligram/tablet (%, w/w is in tablet) |
| Lactose monohydrate, NF | 99(49.5％) |
| Microcrystalline Cellulose, NF | 90(45.0％) |
| Cross-linking sodium carboxymethyl cellulose, NF | 10(5.0％) |
| Magnesium stearate, NF | 1(0.5％) |
| Amount to | 200(100.0％) |
Blend lactose monohydrate, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose in suitable agitator use Turbula or suitable agitator to lubricate by the blend magnesium stearate then.Use conventional tablet press method, the blend after lubricated is pressed into the tablet core of 200 milligrams or approrpiate wts.
Table 2
0.5, the composition and the film weight of the film coating suspension of PPAR α/γ dual antagonist film coating tablet of 1,2,4,8 and 10 milligram
| Intensity (strength) | 0.5 milligram | 1 milligram | 2 milligrams | 4 milligrams | 8 milligrams | 10 milligrams |
| Composition | Content, milligram/tablet (%, w/w is in suspension) | |||||
| The suspension that is used for the first film coatings | ||||||
| PPAR α/γ dual antagonist compd A (peliglitazar) | 0.5 (1.5％) | 1.0 (1.5％) | 2.0 (2.6％) | 4.0 (4.0％) | 8 (5.6％) | 10 (6.06％) |
| Opadry _Orange | 3.0 (9.0％) | 6.0 (9.0％) | 5.0 (6.5％) | 5.0 (5.0％) | 5 (3.5％) | 5 (3.03％) |
| Water * | 30 (8.95％) | 60 (89.5％) | 70 (90.9％) | 91 (91.0％) | 130 (90.9％) | 150 (90.9％) |
| The weight that tablet increases after the first film coatings | 3.5 | 7.0 | 7.0 | 9.0 | 13.0 | 15.0 |
| The suspension that is used for the second film coating layer | |
| Opadry _Orange | 5(10.0％) |
| Water * | 45(90.0％) |
| The weight that tablet increases behind the second film coating layer | 5.0 |
*Water just is used for processing and removes during film coating procedure.
According to hereinafter preparing the suspension that is used for the first film coatings with the listed composition of table 2.
Use mechanical agitator, with PPAR α/γ dual antagonist and Opadry
_Orange (it is a hydroxypropyl emthylcellulose) and water mix.The mixture that makes gained is by homogenizer, to reduce the pharmacy particle size and to form the unit for uniform suspension that contains medicament.
Or this suspension also can be prepared as follows.Be added into PPAR α/γ dual antagonist in the water and make it pass through homogenizer, to reduce the pharmacy particle size.Use mechanical agitator or homogenizer to mix then with the Opadry orange.
Use above-mentioned suspension that the first film coatings is applied on the tablet core, up to the target weightening finish that obtains the first film coatings shown in the table 2.
After the first film coatings drying, the suspension that will have the second film coating layer composition of the listed composition of table 2 is applied on the tablet of film coating layer, up to the weightening finish that additionally obtains about 5 milligrams/tablet.
This bottle of storage is six months in the HDPE bottle that have Cotton Gossypii volume (cotton coil), desiccant by tablet (1 milligram of effectiveness) is packaged in, heat is brought out strip of paper used for sealing (heat induction seal) and under following various storage conditions, and the stability of assessment film coating tablet: described condition is promptly at 5 ℃; At 30 ℃/60% relative humidity (RH); At 40 ℃/75%RH and at 40 ℃/75%RH opening.Tablet also is exposed in the opening petri diss of 40 ℃/75%RH.
Discovery is compared with the tablet with similar composition that uses conventional wet granulation to produce; coated tablet of the present invention has excellent stability; contain the coated pharmaceutical that has similar composition to the present invention in the tablet that described conventional method is produced, but do not contain described medicament in its coatings.
In tabulation under the results are shown in of 1 milligram of tablet.
Table 3
1 milligram of six months stability data rendeing a service spray coating tablet and 1 milligram of moist granule tablet of the present invention
| Compositions | Condition of storage | PPAR α/γ dual antagonist chemical compound | The degradation agent of base catalysis | Acid catalyzed degradation agent | Amount to %I.I | ||
| Initial % | The 4-methoxyphenol | Degradation agent compd A ' | The glycine carbamate | _ alcohol | |||
| The spray coating tablet of embodiment | 5℃ | 100 | - | - | - | - | 1.1 |
| 30℃/60％RH | 100 | - | - | - | - | 1.5 | |
| 40℃/75％RH | 99 | 0.10 | 0.15 | - | - | 1.4 | |
| 40 ℃/75%RH opening | 99 | 0.10 | 0.46 | - | - | 2.4 | |
| Moist granule tablet | 5℃ | 103 | - | - | - | - | 0.5 |
| 30℃/60％RH | 102 | 0.16 | 0.24 | - | - | 1.0 | |
| 40℃/75％RH | 98 | 0.61 | 1.42 | - | - | 2.7 | |
| 40 ℃/75%RH opening | 86 | 0.75 | 5.31 | 0.06 | 0.06 | 8.4 | |
In theory, in the polymer coating layer, high medicament/excipient ratio causes the stability of coated tablet of the present invention (containing 1 milligram of medicament in 10 milligrams of coating polymer) to be better than conventional tablet (containing 1 milligram of medicament in 200 milligrams of tablets).
Batch parameter and the result of peliglitazar tablet are listed in the following table.
Table 4
The coating parameter of peliglitazar film-coated tablet and batch result
| Intensity | 0.5 milligram | 1 milligram | 2 milligrams | 4 milligrams | 8 milligrams | 10 milligrams |
| Lot number | 56678-168 | 56678-143 | 56777-106 | 56777-106 | 56678-164 | 56678-049 |
| Batch size, kilogram | 14 | 14 | 14 | 14 | 17 | 0.6 |
| Dish speed, rpm | 18 | 20 | 17 | 17 | 18 | 25 |
| The suspension flow velocity, mg/ml | 20 | 20 | 20 | 30 | 35 | 5.5 |
| Jet size, millimeter | 0.42 | 0.42 | 0.42 | 0.42 | 0.42 | 1 |
| Atomizing pressure, psi | 39 | 39 | 39 | 45 | 45 | 11 |
| The coating time (first film), hour | 3.0 | 4.5 | 4.5 | 5 | 5.25 | 2.2 |
| Tablet is renderd a service, and % indicates (label) (milligram) | 102 (0.51) | 102 (1.02) | 106 (2.12) | 104 (4.16) | 97 (7.76) | 100.5 (10.05) |
| RSD | 1.8％ | 2.8％ | 2.5％ | 2.7％ | 2.2％ | 1.5％ |
Example 2
Being prepared as follows coating on it has 1 milligram and 8 milligrams of film-coated tablets of PPAR α/γ dual antagonist compd B (Pargluva).
Be prepared as follows the film-coated tablet core that is used for following composition.
Table 5
The composition that is used for film-coated tablet core
| Composition | Content, milligram/tablet (%, w/w is in tablet) | |
| Be used in 1 milligram of tablet | Be used in 8 milligrams of tablets | |
| Lactose monohydrate, NF | 109(54.5％) | 99(49.5％) |
| Microcrystalline Cellulose, NF | 80(40％) | 90(45.0％) |
| Cross-linking sodium carboxymethyl cellulose, NF | 10(5％) | 10(5.0％) |
| Magnesium stearate, NF | 1(0.5％) | 1(0.5％) |
| Amount to | 200(100％) | 200(100.0％) |
Blend lactose monohydrate, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose in suitable agitator use Turbula or suitable agitator to lubricate by the blend magnesium stearate then.Use conventional tablet press method, the blend after lubricated is pressed into the tablet core of 200 milligrams or approrpiate wts.
Table 6
The film coating suspension of 1 and 8 milligram PPAR α/γ dual antagonist (Pargluva) film coating tablet is formed and film weight
| Intensity | 1 milligram | 8 milligrams |
| Composition | Content, milligram/tablet (%, w/w is in suspension) | |
| The suspension that is used for the first film coatings | ||
| PPAR α/γ dual antagonist compd B (Pargluva) | 1.0 (1.6％) | 8 (6.0％) |
| Opadry _Orange | 6.0 (9.6％) | 5 (3.75％) |
| Water * | 55.5 (88.8％) | 120 (90.25％) |
| The weight that tablet increases after the first film coatings | 7.0 | 13.0 |
| The suspension that is used for the second film coating layer | ||
| Opadry _Orange | 5(10.0％) | |
| Water * | 45(90.0％) | |
| The weight that tablet increases behind the second film coating layer | 5.0 | |
*Water just is used for processing and removes during film coating procedure.
Be prepared as follows and have the suspension of forming shown in the table 5 that is used for the first film coatings.
Use mechanical mixer with PPAR α/γ dual antagonist and Opadry
_Orange (hydroxypropyl emthylcellulose just) and water mix.The mixture that makes gained is by homogenizer, to reduce the pharmacy particle size and to form the unit for uniform suspension that contains medicament.
Or this suspension also can be prepared as follows.Add PPAR α/γ dual antagonist in the entry and make it pass through homogenizer and reduce the pharmacy particle size.Use mechanical mixer or homogenizer to sneak into the Opadry orange.
Use above-mentioned suspension that the first film coatings is applied on the tablet core, up to the target weightening finish that obtains the first film coatings shown in the table 6.
After the first film coatings drying, the suspension that will have the second film coating layer composition of the listed composition of table 5 is applied on the tablet of film coating layer, up to the weightening finish that additionally obtains about 5 milligrams/tablet.
Batch parameter of 1 and 8 milligram of tablet and the results are shown in following table.
Table 7
Coating parameter and batch result
| Intensity | 1 milligram | 8 milligrams |
| Lot number | 56678-139 | 53777-069 |
| Batch size | 17 kilograms | 11 kilograms |
| Dish speed | 15rpm | 20rpm |
| The suspension flow velocity | 25 ml/min | 30 ml/min |
| Jet size | 0.7 millimeter | 0.7 |
| Atomizing pressure | 44psi (3 crust) | 44psi (3 crust) |
| The coating time (hour) | 3∶25 | 5∶15 |
| Average tablet is renderd a service | 1.008 milligram | 8.4 milligram |
| RSD | 4.6％ | 3.5％ |
Claims (29)
1. coated tablet, it comprises tablet core and coating at least one coatings thereon, this coatings comprises medicament and at least a coating polymer composition.
2. the coated tablet of claim 1 wherein makes the degraded of this medicament generation base catalysis degraded and/or acid catalysis.
3. the coated tablet of claim 1, wherein this medicament is PPAR α/γ dual antagonist.
4. the coated tablet of claim 3, wherein this medicament is the peliglitazar with following array structure
5. the coated tablet of claim 3, wherein this medicament is the Pargluva with following array structure
6. the coated tablet of claim 1, wherein this coatings is spray-dired coatings.
7. the coated tablet of claim 1, wherein this coatings is to be formed by the coating polymer composition that comprises hydroxypropyl emthylcellulose polymer, polyvinyl alcohol, polyvinyl acetate, ethyl cellulose, methacrylic acid (ester) base polymer or hydroxypropyl cellulose.
8. the coated tablet of claim 1, wherein this coatings is to be formed by the coating polymer composition that comprises the hydroxypropyl emthylcellulose polymer.
9. the coated tablet of claim 1, wherein this coatings comprises hydroxypropyl emthylcellulose, titanium dioxide and acetin.
10. the coated tablet of claim 1, wherein this coatings comprises about 14 to about 67 weight % medicament and the about 30 coating polymer to about 88 weight %.
11. the coated tablet of claim 1, wherein this coating polymer composition is at least about 5 milligrams, cooperates the tablet core with 200 milligrams, and this medicament be tablet core weight at least about 0.1% or 0.2 milligram.
12. the coated tablet of claim 1, it also comprises second coatings that is arranged on this coatings.
13. the coated tablet of claim 12, wherein this second coatings comprises hydroxypropyl emthylcellulose polymer or polyvinyl acetate, polyvinyl alcohol, ethyl cellulose, methacrylic acid (ester) base polymer or hydroxypropyl cellulose.
14. the coated tablet of claim 13, wherein this second coatings comprises the hydroxypropyl emthylcellulose polymer.
15. the coated tablet of claim 12, wherein this coatings and second coatings are represented substantially the same hydroxypropyl emthylcellulose polymer respectively.
16. the coated tablet of claim 1, it comprises about 0.1 medicament to about 70 weight %, is benchmark with final tablet weight.
17. the coated tablet of claim 15, wherein this medicament is the peliglitazar with following array structure
18. the coated tablet of claim 15, wherein this medicament is the Pargluva with following array structure
19. the coated tablet of claim 1, wherein the amount of this medicament is about 0.1 to about 25 milligrams, and the amount of coating polymer is about 1 to about 50 milligrams, and optional comprises that second coatings that is arranged on this coatings, the amount of this second coatings are about 1 to about 50 milligrams.
20. the coated tablet of claim 1, wherein this tablet core comprises one or more filleies, optional one or more binding agents, one or more disintegrating agents, and one or more tabletting lubricants.
21. the coated tablet of claim 17, wherein this tablet core comprises microcrystalline Cellulose, lactose monohydrate, cross-linking sodium carboxymethyl cellulose and magnesium stearate.
22. the coated tablet of claim 1, it has following composition:
Tablet core Account for the weight % of tablet core
Microcrystalline Cellulose 20 to 75 weight %
Lactose monohydrate 20 to 75 weight %
Cross-linking sodium carboxymethyl cellulose 2 to 10 weight %
Magnesium stearate 0.2 to 2 weight %
First coatings
Medicament 0.2 to 50 milligrams
Hydroxypropyl emthylcellulose or polyvinyl alcohol coating material 20 to 180 milligrams
Second coatings
Hydroxypropyl emthylcellulose or polyvinyl alcohol coating material 2 to 15 milligrams
Wherein this medicament has following array structure:
23. the coated tablet of claim 22, wherein for 10 milligrams effectiveness, coatings comprises 10 milligrams of medicaments and 5 milligrams of polymer class coating materials, and for 1 milligram effectiveness, coatings comprises 1 milligram of medicament and 6 milligrams of polymer class coating materials.
24. a coated tablet, it comprises:
A) tablet core, it comprises one or more excipient and optional one or more active ingredients and one or more optional medicaments;
B) coating at least one coatings on tablet core, this layer comprises at least a medicament and at least a coating polymer composition; And
C) second coatings the optional coatings b that is arranged in), this second coatings comprises the coating polymer composition.
25. the coated tablet of claim 1, it has following composition:
Tablet core
Composition Content, milligram/tablet (%, w/w is in tablet)
Lactose monohydrate, NF 99(49.5％)
Microcrystalline Cellulose, NF 90(45.0％)
Cross-linking sodium carboxymethyl cellulose, NF 10(5.0％)
Magnesium stearate, NF 1(0.5％)
Amount to 200(100.0％)
Blend lactose monohydrate, microcrystalline Cellulose and cross-linking sodium carboxymethyl cellulose in suitable agitator, use Turbula or suitable agitator to lubricate then by the blend magnesium stearate, use conventional tablet press method, the blend after lubricated is pressed into the tablet core of 200 milligrams or approrpiate wts.
0.5, the composition and the film weight of the film coating layer of 1,2,4,8 and 10 milligram peliglitazar film coating tablet
Intensity 0.5 milligram 1 milligram 2 milligrams 4 milligrams 8 milligrams 10 milligrams
Composition Content, milligram/tablet (%, w/w is in suspension)
The first film coatings
PPAR α/γ dual antagonist peliglitazar-compd A 0.5 (1.5％) 1.0 (1.5％) 2.0 (2.6％) 4.0 (4.0％) 8 (5.6％) 10 (6.06％)
Hydroxypropyl emthylcellulose 3.0 (9.0％) 6.0 (9.0％) 5.0 (6.5％) 5.0 (5.0％) 5 (3.5％) 5 (3.03％)
Water
* 30 (8.95％) 60 (89.5％) 70 (90.9％) 91 (91.0％) 130 (90.9％) 150 (90.9％)
The weight that tablet increases after the first film coatings 3.5 7.0 7.0 9.0 13.0 15.0
The second film coating layer
Hydroxypropyl emthylcellulose 5(10.0％)
Water
* 45(90.0％)
The weight that tablet increases behind the second film coating layer 5.0
*Water just is used for processing and removes during film coating procedure.
26. the coated tablet of claim 1, it has following composition:
Tablet core
Composition Content, milligram/tablet (%, w/w is in tablet)
Be used in 1 milligram of tablet Be used in 8 milligrams of tablets
Lactose monohydrate, NF 109(54.5％) 99(49.5％)
Microcrystalline Cellulose, NF 80(40％) 90(45.0％)
Cross-linking sodium carboxymethyl cellulose, NF 10(5％) 10(5.0％)
Magnesium stearate, NF 1(0.5％) 1(0.5％)
Amount to 200(100％) 200(100.0％)
The composition of the film coating layer of 1 and 8 milligram Pargluva film coating tablet and film weight
Intensity 1 milligram 8 milligrams
Composition Content, milligram/tablet (%, w/w is in suspension)
The first film coatings
PPAR α/γ dual antagonist Pargluva-compd B 1.0(1.6％) 8(6.0％)
Hydroxypropyl emthylcellulose 6.0 (9.6％) 5 (3.75％)
Water
* 55.5(88.8％) 120(90.25％)
The weight that tablet increases after the first film coatings 7.0 13.0
The second film coating layer
Hydroxypropyl emthylcellulose 5(10.0％)
Water
* 45(90.0％)
The weight that tablet increases behind the second film coating layer 5.0
*Water just is used for processing and removes during film coating procedure.
27. one kind prepare comprise tablet core and thereon coating the method for the coated tablet of at least one coatings is arranged, this coatings comprises medicament and at least a coating polymer, this method comprises coatings is applied on one or more tablet core, and the tablet of dry coationg.
28. the method for claim 27, wherein this coatings is that form with the suspension of coating polymer applies.
29. the method for claim 27, it may further comprise the steps: on coatings, apply second coatings, and dry so tablet core of coating.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55633104P | 2004-03-25 | 2004-03-25 | |
| US60/556,331 | 2004-03-25 | ||
| US60/648,872 | 2005-02-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1946376A true CN1946376A (en) | 2007-04-11 |
Family
ID=38045431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200580012622.5A Pending CN1946376A (en) | 2004-03-25 | 2005-03-22 | Coated tablet composition and method of manufacturing the same |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1946376A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102846568A (en) * | 2012-08-27 | 2013-01-02 | 辽宁王牌速效制药有限公司 | Preparation method of cephalexin layering digestion tablet |
| CN106306029A (en) * | 2015-06-30 | 2017-01-11 | 中国航天员科研训练中心 | Portable full nutritional yoghurt for spaceflight, yoghurt sheet, and preparation method thereof |
| CN109908099A (en) * | 2011-05-13 | 2019-06-21 | Eb Ip希博里塔布斯有限责任公司 | Drug delivery system |
| CN114007593A (en) * | 2019-04-26 | 2022-02-01 | 应用材料公司 | Coated pharmaceutical composition and preparation method thereof |
-
2005
- 2005-03-22 CN CN200580012622.5A patent/CN1946376A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109908099A (en) * | 2011-05-13 | 2019-06-21 | Eb Ip希博里塔布斯有限责任公司 | Drug delivery system |
| CN102846568A (en) * | 2012-08-27 | 2013-01-02 | 辽宁王牌速效制药有限公司 | Preparation method of cephalexin layering digestion tablet |
| CN106306029A (en) * | 2015-06-30 | 2017-01-11 | 中国航天员科研训练中心 | Portable full nutritional yoghurt for spaceflight, yoghurt sheet, and preparation method thereof |
| CN114007593A (en) * | 2019-04-26 | 2022-02-01 | 应用材料公司 | Coated pharmaceutical composition and preparation method thereof |
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