CN103655505A - Pain relieving bilayer controlled-release tablet and preparation method thereof - Google Patents
Pain relieving bilayer controlled-release tablet and preparation method thereof Download PDFInfo
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Abstract
The invention provides a pain relieving bilayer controlled-release tablet which comprises a quick release layer and a slow release layer, wherein holes are formed in the slow release layer; the holes are filled with quick release particles; the quick release layer and the quick release particles consist of pain relieving drugs and pharmaceutical adjuvant; the slow release layer consists of pain relieving drugs, slow release materials and pharmaceutical adjuvant. The pain relieving bilayer controlled-release tablet has the following technical effects: 1) the bilayer tablet has better physical stability than a common bilayer tablet, so that the storage and the transportation are convenient; 2) the disintegration time limit of the quick release layer of the bilayer controlled-release tablet is 10-30 seconds through the detection of the dissolving experiment; the slow release layer presents the zero-level release mode; the medicine taking effectiveness and safety of patients are largely improved. In the preparation process of the bilayer tablet, the quick release particles are filled in the holes. The quick disintegration of the quick release layer after the medicine taking is guaranteed through the drug release mode of combining the quick release with the slow release, so that the blood concentration can quickly achieve the range of a therapeutic window; the slow release layer is slowly released in a longer time period to continuously maintain the treatment effect; the toxic or side effects are effectively controlled.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of pain relieving class two-layer release-controlled tablet and preparation method thereof.
Background technology
The oral solid formulation that the tablet of take is representative is most convenient, safest administering mode, in the clinical practice of medicine, market sale and research and development always in occupation of main body and leading position.At present by changing the preparation method of tablet, guarantee that medicine keeps the rock-steady structure of double-layer tablet and efficacy enhancing and toxicity reducing that regulation and control release realizes medicine to become the tool demand of pharmaceuticals industry and practical new agent technology at shelf life.Double-layer tablet be a kind of on osmotic pump controlled release tablet basis, grow up contain double-deck novel two-phase medicine-releasing system, its structure is different with the difference of purpose of design.Compare with common single-layer sheet, double-layer tablet has many advantages in clinical practice, it not only can combine the pharmacokinetics behavior that reaches desirable by two kinds of medicines or same medicine with different release modes, and can improve the stability that has compatibility reaction medicine, can also give tablet special function.
Double-layer tablet is generally divided into single medicine double-layer tablet and compound double-layer tablet, single medicine double-layer tablet comprises single medicine rapid release double-layer tablet, single medicine sustained-release double-layer tablet and single medicine speed/sustained-release double-layer tablet, wherein single medicine speed/sustained-release double-layer tablet is the more common double-layer tablet of a class, be mainly drug-time curve behavior in the body that reaches best and design, generally by rapid release and two kinds of granule compactings of slow release, formed, release layer contributes to quick mitigation symptoms, and slow release layer, for maintaining effective dose, is realized quick-acting and long-acting combination.
Pain not only affects quality of life, has people also can produce mental illness because long-term pain can not get effectively treatment.A lot of pain-suffered patients, due to treatment not in time, make local long-term general pain be converted into complicated local pain syndrome or central pain, become the painful diseases of refractory.So, pain relieving in time.Ibuprofen ibuprofen modified release capsule in 1991 in Discussion on Chinese Listed, by one of safest nonsteroidal anti-inflammatory drug (NSAIDS)---ibuprofen has been introduced China in the world, 12 hours slow release methods that it is exclusive, make ibuprofen effectively pain relieving lastingly, and safe secondary effect is low, use more conveniently simultaneously, successfully filled up the blank of China in slow releasing capsule processing technology.
Be below the technology of existing double-layer tablet:
CN101073563B discloses a kind of hand-type compositions that contains (S)-ibuprofen and LEVO CITRAZINE and releases slowly double-layer tablet, proposes a kind of release layer that contains (S)-ibuprofen and LEVO CITRAZINE and only contains the double-layer tablet of the slow release layer of (S)-ibuprofen.Can reach rapid alleviation cold symptoms, the effect of long-acting performance antipyretic-antalgic.
CN102188423B discloses spectinomycin hydrochloride and felodipine sustained-release double-layer tablet and preparation method thereof, proposes double-layer tablet and is respectively spectinomycin hydrochloride slow release layer and felodipine sustained-release layer.
CN102283829B antimalarial pharmaceutical composition and preparation method and purposes, after pharmaceutical composition of the present invention is granulated Artemether and benflumetol respectively, be prepared into double-layer tablet, avoided the mixed process of Artemether and benflumetol, guaranteed the safety in compound recipe preparation process; And the disintegrate of gained double-layer tablet is rapid, to compare with existing compound tablet, effective ingredient dissolution significantly improves.
CN101084904B discloses cefixime sustained-release double-layer tablet, proposes the double-layer tablet that a kind of release layer and slow release layer combine, and the slow release layer release in vitro time is more than 12 hours.
CN102188425B double-layer tablet that comprises hydrochloric acid and simvastatin and preparation method thereof, proposition adds nicotinic acid in simvastatin release layer, the composition of two kinds of lamellas is approached, and elastic deformation is also comparatively approaching, and the phenomenon of separation, sliver can not occur in process of production.
In above-mentioned technology, because double-layer tablet is generally suppressed by I layer and the gradation of II layer, therefore, can cause medicine in transportation and the storage process Chinese medicine tablet unfavorable result such as split.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art part, a kind of pain relieving class two-layer release-controlled tablet and preparation method thereof is provided.The release model that rapid release/slow release of the present invention combines, can reach quickly alleviating pain long-time inhibition of pain, improves patients ' life quality.
Pain relieving class two-layer release-controlled tablet of the present invention, comprise release layer and slow release layer, described slow release layer is porose, in described hole, be filled with immediate-release granules, described release layer and immediate-release granules form by pain relieving class medicine and pharmaceutic adjuvant, and described slow release layer is comprised of pain relieving class medicine, slow-release material and pharmaceutic adjuvant.
The diameter in the hole of described slow release layer is 1～10mm.
The diameter in the hole of described slow release layer is 3～6mm.
Described pain relieving class medicine is selected from aspirin, magnesium salicylate, sodium salicylate, choline magnesium trisalicylate, diflunisal, salsalate, ibuprofen, indomethacin, flurbiprofen, fenoprofen, naproxen, nabumetone, piroxicam, Phenylbutazone, diclofenac, venlofen, ketone ibuprofen, ketorolac, four clofenamic acides, sulindac, tolmetin or Anisodamine, or a kind of in the derivant of above-claimed cpd; Described slow-release material is selected from one or more of hydroxypropyl methylcellulose, ethyl cellulose, hydroxypropyl cellulose; Described pharmaceutic adjuvant is selected from one or more in filler, disintegrating agent, lubricant, binding agent, fluidizer.
Described two-layer release-controlled tablet, described filler is selected from one or more of lactose monohydrate, lactose, pre-paying starch and microcrystalline Cellulose; Described disintegrating agent is selected from one or more in sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium and polyvinylpolypyrrolidone; Described lubricant be selected from stearic acid, magnesium stearate and talcous one or more; Described binding agent is selected from one or more of polyvidone, hydroxypropyl cellulose and hydroxypropyl methylcellulose; Described fluidizer is silicon dioxide.
Described two-layer release-controlled tablet, in described slow release layer, comprises following component according to percentage by weight:
In described release layer and immediate-release granules, according to percentage by weight, comprise following component:
Described two-layer release-controlled tablet also comprises coatings, and described coatings comprises following component according to percentage by weight:
The preparation method of pain relieving class two-layer release-controlled tablet of the present invention, is characterized in that, comprises the following steps:
1) pain relieving class medicine and slow-release material and pharmaceutic adjuvant are mixed and made into slow-releasing granules; Pain relieving class medicine and pharmaceutic adjuvant are mixed and made into immediate-release granules;
2) slow-releasing granules is pressed into porose slow release layer, then slow release layer is reentered in the punch die of tablet machine, filling immediate-release granules, suppresses for the second time, forms the double-layer tablet being comprised of release layer and slow release layer, wherein in the hole of slow release layer, is filled with immediate-release granules.
The preparation method of described pain relieving class two-layer release-controlled tablet, also comprises the step of coating.
Also comprise in addition the step of coating.
The present invention has following technique effect:
1) the double-layer tablet physical stability that prepared by the present invention is better than common double synusia, is more conducive to store and transportation.Because the slow release layer of two-layer release-controlled tablet is porose, immediate-release granules in pressing process in natural ostium, makes double-layer tablet in conjunction with closely, store and transportation in not easily separated.
2) through dissolution test, to detect release layer disintegration be 10～30 seconds to this two-layer release-controlled tablet, and slow release layer is zero level release mode, has improved greatly effectiveness and safety that patient takes medicine.In double-layer tablet preparation process, in hole, be filled with immediate-release granules.After the drug release mode that rapid release combines with slow release has guaranteed to take medicine, the quick disintegrate of release layer, makes blood drug level can reach fast treatment window scope, and slow release layer is slowly released in and in long period of time, continues to maintain therapeutical effect, and effectively controls toxic and side effects.
Accompanying drawing explanation
Fig. 1 is the structure chart of the single hole double-layer tablet prepared of the present invention;
Fig. 2 is the structure chart of the diplopore double-layer tablet prepared of the present invention;
Fig. 3 is the structure chart of the three hole double-layer tablet prepared of the present invention;
Fig. 4 is the impact of slow release layer different pore size on stripping;
Fig. 5 is embodiment 1 two-layer release-controlled tablet release in vitro curve;
Fig. 6 is the external release profiles of embodiment 2 two-layer release-controlled tablet sheet;
Fig. 7 is the external release profiles of embodiment 3 two-layer release-controlled tablet sheet;
Fig. 8 is the external stripping curve of embodiment 4 two-layer release-controlled tablet sheet.
Wherein, 1 is slow release layer; 2 is release layer; 3 is hole.
The specific embodiment.
The prescription of the two-layer release-controlled tablet of embodiment 1-5 is as following table:
The prescription of the two-layer release-controlled tablet of each embodiment (1000, g)
Above-mentioned double-layer tablet can be used coating, and coatings contains following component:
| Hydroxypropyl methyl fiber is E5 | 30 |
| |
14 |
| |
5 |
| |
2 |
| 80% alcohol-water solution | In right amount |
The prescription of the two-layer release-controlled tablet of the present embodiment is as shown in table 1.Its preparation method is as follows:
1, prepare slow-releasing granules:
(1) weigh Zolpidemtar Trate and the hydroxypropyl methylcellulose K100LV of 60 mesh sieves excessively of recipe quantity, K4M, lactose fully mixes, and adds afterwards silicon dioxide and the magnesium stearate of recipe quantity 1/2nd.The material mixing is transferred in wet granulator;
(2) alcoholic solution that compound concentration is 70% is to the soft material processed of the mixture in step 1;
(3) soft material making is carried out to granulate with 24 mesh sieves;
(4) be dried and sieve granule
(5) obtain slow-releasing granules, be used to form slow release layer.
2, prepare immediate-release granules:
(1) by the Zolpidemtar Trate of recipe quantity, lactose, microcrystalline Cellulose, polyvidone mixed 60 mesh sieves, added half silicon dioxide and magnesium stearate of recipe quantity, mix homogeneously in batch mixer;
(2) alcoholic solution that compound concentration is 80% is to the soft material processed of the mixture in step 1;
(3) soft material making is carried out to granulate with 24 mesh sieves;
(4) be dried and sieve powder particles;
(5) according to outer addition, adding cross-linking sodium carboxymethyl cellulose mixs homogeneously with dry granule;
(6) obtain immediate-release granules, be used to form release layer and for filling the hole of slow release layer.
3, prepare two-layer release-controlled tablet:
(1) slow release layer granule is added to remaining silicon dioxide and magnesium stearate and be pressed into middle porose slow releasing tablet, aperture is respectively 3mm, 4mm, 6mm; Also suppressed in addition the slow releasing tablet that there is no hole;
(2) slow releasing tablet is reentered in the punch die of tablet machine, filling release layer granule, rushes in row compacting for the second time by scrobicula, forms double-layer tablet;
(3) HPMC E5 of recipe quantity being dispersed in to concentration is in 80% ethanol, adds polysorbate80 after swelling, and stirring and dissolving is complete, then adds titanium dioxide and Pulvis Talci, stir, after filtration as coating solution;
(4) by double-layer tablet coating, make every weightening finish 5%, then dry solidification.
In order to investigate the impact of slow release layer aperture on stripping, that the present embodiment is first suppressed into slow release layer is not with holes, with 3mm hole, with 4mm hole, with the slow releasing tablet in 6mm aperture, carries out stripping experiment, and slow release layer aperture is larger, and dissolution rate is faster.The results are shown in Figure 4.
The double-layer tablet preparing is carried out to stripping experiment, the effect of slow release after the first rapid release of investigation tablet, 0.5h samples detection, and release layer stripping completely, the results are shown in Figure 5.
The prescription of the two-layer release-controlled tablet of the present embodiment is as shown in table 1.Its preparation method is as follows:
1, prepare slow-releasing granules:
(1) weigh Zolpidemtar Trate and the hydroxypropyl methylcellulose K100LV of 60 mesh sieves excessively of recipe quantity, K4M, lactose fully mixes, and adds afterwards silicon dioxide and the magnesium stearate of recipe quantity 1/2nd.The material mixing is transferred in wet granulator;
(2) alcoholic solution that compound concentration is 75% is to the soft material processed of the mixture in step 1;
(3) soft material making is carried out to granulate with 24 mesh sieves;
(4) be dried and sieve granule
(5) obtain slow-releasing granules, be used to form slow release layer.
2, prepare immediate-release granules:
(1) by the Zolpidemtar Trate of recipe quantity, lactose, microcrystalline Cellulose and hydroxypropyl cellulose-HF, sodium carboxymethyl cellulose mixed 60 mesh sieves, added half silicon dioxide and magnesium stearate of recipe quantity, mix homogeneously in batch mixer;
(2) alcoholic solution that compound concentration is 90% is to the soft material processed of the mixture in step 1;
(3) soft material making is carried out to granulate with 24 mesh sieves;
(4) be dried and sieve powder particles
(5) obtain immediate-release granules, be used to form release layer and for filling the hole of slow release layer.
3, prepare two-layer release-controlled tablet:
(1) slow release layer granule is added to remaining silicon dioxide and magnesium stearate and be pressed into middle porose slow releasing tablet, aperture is respectively 4mm, 6mm;
(2) slow releasing tablet is reentered in the punch die of tablet machine, filling release layer granule, rushes in row compacting for the second time by scrobicula, forms double-layer tablet;
(3) HPMC E5 of recipe quantity being dispersed in to concentration is in 80% ethanol, adds polysorbate80 after swelling, and stirring and dissolving is complete, then adds titanium dioxide and Pulvis Talci, stir, after filtration as coating solution;
(4) by double-layer tablet coating, make every weightening finish 5%, then dry solidification.
Investigate double-layer tablet release layer disintegration rate, and the effect of slow release after the first rapid release of double-layer tablet, 0.25h sample detection, and release layer stripping, over 85%, the results are shown in Figure 6.
The prescription of the two-layer release-controlled tablet of the present embodiment is as shown in table 1.Its preparation method is as follows:
1, prepare slow-releasing granules:
(1) weigh zopiclone and the hydroxypropyl methylcellulose K100LV of 60 mesh sieves excessively of recipe quantity, K4M, lactose fully mixes, and adds afterwards silicon dioxide and the magnesium stearate of recipe quantity 1/2nd.The material mixing is transferred in wet granulator;
(2) alcoholic solution that compound concentration is 80% is to the soft material processed of the mixture in step 1;
(3) soft material making is carried out to granulate with 24 mesh sieves;
(4) be dried and sieve granule
(5) obtain slow-releasing granules, be used to form slow release layer.
2, prepare immediate-release granules:
(1) by the zopiclone of recipe quantity, lactose, microcrystalline Cellulose and hydroxypropyl cellulose-HF, sodium carboxymethyl cellulose mixed 60 mesh sieves, added half silicon dioxide and magnesium stearate of recipe quantity, mix homogeneously in batch mixer;
(2) alcoholic solution that compound concentration is 90% is to the soft material processed of the mixture in step 1;
(3) soft material making is carried out to granulate with 24 mesh sieves;
(4) be dried and sieve powder particles
(5) obtain immediate-release granules, be used to form release layer and for filling the hole of slow release layer.
3, prepare two-layer release-controlled tablet:
(1) slow release layer granule is added to remaining silicon dioxide and magnesium stearate and be pressed into middle porose slow releasing tablet, aperture is respectively 4mm, 6mm;
(2) slow releasing tablet is reentered in the punch die of tablet machine, filling release layer granule, rushes in row compacting for the second time by scrobicula, forms double-layer tablet;
(3) HPMC E5 of recipe quantity being dispersed in to concentration is in 80% ethanol, adds polysorbate80 after swelling, and stirring and dissolving is complete, then adds titanium dioxide and Pulvis Talci, stir, after filtration as coating solution;
(4) by double-layer tablet coating, make every weightening finish 5%, then dry solidification.
The double-layer tablet preparing is carried out to stripping experiment, the effect of slow release after the first rapid release of investigation tablet, 0.5h samples detection, and release layer stripping completely, the results are shown in Figure 7.
Embodiment 4
The prescription of the two-layer release-controlled tablet of the present embodiment is as shown in table 1.Its preparation method is as follows:
1, prepare slow-releasing granules:
(1) weigh Zaleplon and the hydroxypropyl methylcellulose K100LV of 60 mesh sieves excessively of recipe quantity, K4M, lactose fully mixes, and adds afterwards silicon dioxide and the magnesium stearate of recipe quantity 1/2nd.The material mixing is transferred in wet granulator;
(2) alcoholic solution that compound concentration is 80% is to the soft material processed of the mixture in step 1;
(3) soft material making is carried out to granulate with 24 mesh sieves;
(4) be dried and sieve granule
(5) obtain slow-releasing granules, be used to form slow release layer.
2, prepare immediate-release granules:
(1) by the Zaleplon of recipe quantity, lactose, microcrystalline Cellulose and hydroxypropyl cellulose-HF, sodium carboxymethyl cellulose mixed 60 mesh sieves, added half silicon dioxide and magnesium stearate of recipe quantity, mix homogeneously in batch mixer;
(2) alcoholic solution that compound concentration is 90% is to the soft material processed of the mixture in step 1;
(3) soft material making is carried out to granulate with 24 mesh sieves;
(4) be dried and sieve powder particles
(5) obtain immediate-release granules, be used to form release layer and for filling the hole of slow release layer.
3, prepare two-layer release-controlled tablet:
(1) slow release layer granule is added to remaining silicon dioxide and magnesium stearate and be pressed into middle porose slow releasing tablet, aperture is respectively 4mm, 6mm;
(2) slow releasing tablet is reentered in the punch die of tablet machine, filling release layer granule, rushes in row compacting for the second time by scrobicula, forms double-layer tablet;
(3) HPMC E5 of recipe quantity being dispersed in to concentration is in 80% ethanol, adds polysorbate80 after swelling, and stirring and dissolving is complete, then adds titanium dioxide and Pulvis Talci, stir, after filtration as coating solution;
(4) by double-layer tablet coating, make every weightening finish 5%, then dry solidification.
Prepare monolayer fast-release tablet and double-layer tablet and carry out stripping experiment, investigate tablet release layer disintegration rate, and the effect of slow release after the first rapid release of double-layer tablet, 0.5h sample detection, and release layer stripping, over 90%, the results are shown in Figure 8.
The prescription of the two-layer release-controlled tablet of the present embodiment is as shown in table 1.Its preparation method is with embodiment 3.
According to the method in embodiment 1, having prepared slow release layer does not have hole (double-layer tablet being simply comprised of one deck slow release one deck rapid release), slow release layer to have 3mm hole, a slow release layer to have a 4mm hole and slow release layer to have respectively 100 of the double-layer tablet in a 6mm hole, in friability detector, carry out respectively friability experiment comparative study, result is as table 2:
Table 2
As can be seen from Table 2, supplementary material form and the on all four situation of proportioning under, the sheet number that layering occurs in upset is collided for 100 double-layer tablet that there is no a hole has 8.Separately get with 100, porose double-layer tablet 6mm aperture, 100,4mm aperture, 100,3mm aperture and carry out same experimentation, result show aperture large compared with cracky, but all without the phenomenon of lamella separation.
According to the method in embodiment 4, having prepared slow release layer does not have hole, slow release layer to have 3mm hole, slow release layer to have 4mm hole and slow release layer to have each 20 of the double-layer tablet in 6mm hole, is positioned in stability test case, humidity is set as RH95%, temperature is made as 25 ℃, observes after placing 24h, and result is as following table 3:
Table 3
Slow release layer do not have hole 20 middle levels separation have 18, porose appearance that there is no layering.
In this prescription release layer, contain super-disintegrant, the hygroscopicity of disintegrating agent is stronger, and when ambient humidity is larger, release layer is larger than slow release layer degrees of expansion, does not have the double-layer tablet levels in hole easily separated.After slow release layer band is porose, the immediate-release granules moisture expantion in hole, release layer engages tightr with slow release layer.Therefore in experimentation with porose double-layer tablet all without segregation phenomenon.
According to the method for embodiment 3, having suppressed respectively slow release layer does not have the double-layer tablet in hole, hole of slow release layer, two holes of slow release layer and three holes of slow release layer, owing to only containing active component and excipient in release layer, do not contain binding agent, respectively get 20, in friability detector, carry out respectively friability experiment comparative study, result is as table 4:
Table 4
From the above results, can find out, double-layer tablet physical stability prepared by the present invention is better than common double synusia, is more conducive to store and transportation.
Claims (9)
1. a pain relieving class two-layer release-controlled tablet, comprise release layer and slow release layer, it is characterized in that, described slow release layer is porose, in described hole, be filled with immediate-release granules, described release layer and immediate-release granules form by pain relieving class medicine and pharmaceutic adjuvant, and described slow release layer is comprised of pain relieving class medicine, slow-release material and pharmaceutic adjuvant.
2. two-layer release-controlled tablet according to claim 1, is characterized in that, the diameter in the hole of described slow release layer is 1～10mm.
3. two-layer release-controlled tablet according to claim 2, is characterized in that, the diameter in the hole of described slow release layer is 3～6mm.
4. two-layer release-controlled tablet according to claim 1, it is characterized in that, described pain relieving class medicine is selected from aspirin, magnesium salicylate, sodium salicylate, choline magnesium trisalicylate, diflunisal, salsalate, ibuprofen, indomethacin, flurbiprofen, fenoprofen, naproxen, nabumetone, piroxicam, Phenylbutazone, diclofenac, venlofen, ketone ibuprofen, ketorolac, four clofenamic acides, sulindac, tolmetin or Anisodamine, or a kind of in the derivant of above-claimed cpd; Described slow-release material is selected from one or more of hydroxypropyl methylcellulose, ethyl cellulose, hydroxypropyl cellulose; Described pharmaceutic adjuvant is selected from one or more in filler, disintegrating agent, lubricant, binding agent, fluidizer.
5. two-layer release-controlled tablet according to claim 4, is characterized in that, described filler is selected from one or more of lactose monohydrate, lactose, pre-paying starch and microcrystalline Cellulose; Described disintegrating agent is selected from one or more in sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium and polyvinylpolypyrrolidone; Described lubricant be selected from stearic acid, magnesium stearate and talcous one or more; Described binding agent is selected from one or more of polyvidone, hydroxypropyl cellulose and hydroxypropyl methylcellulose; Described fluidizer is silicon dioxide.
6. two-layer release-controlled tablet according to claim 4, is characterized in that,
In described slow release layer, according to percentage by weight, comprise following component:
In described release layer and immediate-release granules, according to percentage by weight, comprise following component:
7. two-layer release-controlled tablet according to claim 1, is characterized in that, also comprises coatings, and described coatings comprises following component according to percentage by weight:
8. the preparation method of the pain relieving of any one described in claim 1～6 class two-layer release-controlled tablet, is characterized in that, comprises the following steps:
1) pain relieving class medicine and slow-release material and pharmaceutic adjuvant are mixed and made into slow-releasing granules; Pain relieving class medicine and pharmaceutic adjuvant are mixed and made into immediate-release granules;
2) slow-releasing granules is pressed into porose slow release layer, then slow release layer is reentered in the punch die of tablet machine, filling immediate-release granules, suppresses for the second time, forms the double-layer tablet being comprised of release layer and slow release layer, wherein in the hole of slow release layer, is filled with immediate-release granules.
9. the preparation method of the two-layer release-controlled tablet of pain relieving class as described in claim 8, is characterized in that, also comprises the step of coating.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310716482.6A CN103655505B (en) | 2013-12-23 | 2013-12-23 | A kind of pain relieving class two-layer release-controlled tablet and preparation method thereof |
| ES14874251T ES2712129T3 (en) | 2013-12-23 | 2014-12-19 | Double-layer tablet and method of preparation |
| PCT/CN2014/094367 WO2015096668A1 (en) | 2013-12-23 | 2014-12-19 | Double-layer tablet and preparation method thereof |
| DK14874251.3T DK3087980T3 (en) | 2013-12-23 | 2014-12-19 | DOUBLE LAYER TABLE AND METHOD OF PRODUCING THEREOF |
| EP14874251.3A EP3087980B1 (en) | 2013-12-23 | 2014-12-19 | Double-layer tablet and preparation method thereof |
| JP2016543032A JP6296371B2 (en) | 2013-12-23 | 2014-12-19 | Preparation method of bilayer tablet |
| US15/107,892 US10137092B2 (en) | 2013-12-23 | 2014-12-19 | Double-layer tablet and preparation method thereof |
| US16/178,547 US10925836B2 (en) | 2013-12-23 | 2018-11-01 | Double-layer tablet and painkiller tablet with same structure |
| US16/178,543 US10940114B2 (en) | 2013-12-23 | 2018-11-01 | Hypnotics tablet with double-layer structure |
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Cited By (5)
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| WO2015096668A1 (en) * | 2013-12-23 | 2015-07-02 | 闻晓光 | Double-layer tablet and preparation method thereof |
| CN109316457A (en) * | 2018-11-26 | 2019-02-12 | 正大制药（青岛）有限公司 | A kind of cyclobenzaprine hydrochloride sustained release preparation and preparation method thereof |
| CN110037994A (en) * | 2019-05-24 | 2019-07-23 | 中国药科大学 | A kind of brufen quick-release and slow-release double-layer tablets and preparation method thereof |
| CN110368371A (en) * | 2014-04-08 | 2019-10-25 | 越洋医药开发(广州)有限公司 | A kind of novel controlled release piece |
| CN114177155A (en) * | 2020-09-08 | 2022-03-15 | 越洋医药开发(广州)有限公司 | Ibuprofen controlled release tablet and preparation method thereof |
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