CN103690505A - Hypnotic double-layer controlled release tablet and preparation method thereof - Google Patents
Hypnotic double-layer controlled release tablet and preparation method thereof Download PDFInfo
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Abstract
The invention provides a hypnotic double-layer controlled release tablet, comprising a rapid-release layer and a slow-release layer, wherein the rapid-release layer is provided with pores which are filled with rapid-release particles; the rapid-release layer and the rapid-release particles are composed of hypnotic drug and pharmaceutical excipients; the slow-release layer is composed of a hypnotic drug, a slow-release material and pharmaceutical excipients. The hypnotic double-layer controlled release tablet has the following technical effects that 1) the physical stability of the double-layer tablet provided by the invention is better than that of the common double-layer table, which is advantageous for storage and transportation, and 2) a dissolution test detects that the disintegration time limit of the rapid-release layer of the double-layer tablet provided by the invention ranges from 20 seconds to 30 seconds; and the slow-release layer is in a zero-order release pattern, and therefore the effectiveness and safety of medication for a patient are greatly improved. In the preparation process of the double-layer tablet, the rapid-release particles fill in the pores. The drug release pattern of combined rapid release and slow release guarantees that the rapid-release layer is disintegrated rapidly after the drug is taken; as a result, the blood concentration is capable of quickly reaching the therapeutic window range; the slow-release layer is slowly released so that the therapeutic action is maintained for a long period of time and toxic and side effects are effectively controlled.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of class two-layer release-controlled tablet and preparation method thereof of sleeping peacefully.
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 general is 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.
Insomniac selects safe sleeping pill to be more conducive to healthy and Cure for insomnia.More can successful Cure for insomnia and be conducive to health without addicted hypnotic and safe sleeping pill, avoid the serious harm of having a sleepless night.Take as required the safe medicine of sleeping peacefully and be more conducive to healthy and Cure for insomnia.Country supports pharmacy actively rationally to sell safe hypnotic in order to public health.Country also encourages pharmacy to sell the less hypnotic of side effect in order to people ' s health and pharmacy's benefit, and many hypnotic are not psychotropic substances, and suitably taking sleeping pill and hypnotic is the successful means of Cure for insomnia.
All can sleep, extend the medicine of total sleep time and deep sleep's process by rapid induction, all contributes to Cure for insomnia.
The medicine of at present conventional Cure for insomnia has sedative hypnotic (comprising barbiturates, Benzodiazepines, atypia Benzodiazepines), antidepressants, antihistaminic (at present seldom for hypnosis) and Chinese medicine.
Be below the technology of existing double-layer tablet:
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.
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.
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 class two-layer release-controlled tablet and preparation method thereof of sleeping peacefully is provided.The release mode that the rapid release/slow release proposing in the present invention combines, can reach quick sleep and extend the length of one's sleep, improves the object of sleep quality.
The class two-layer release-controlled tablet of sleeping peacefully 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 are comprised of sleep peacefully class medicine and pharmaceutic adjuvant, and described slow release layer is comprised of sleep peacefully 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.
The described class medicine of sleeping peacefully is selected from zolpidem, Zaleplon, zopiclone, triazolam, midazolam, flurazepam, diazepam, chlordiazepoxide, nitrazepam, estazolam, alprazolam or lorazepam, or a kind of in the derivant of above-claimed cpd; Described slow-release material is selected from one or more in hydroxypropyl methylcellulose, ethyl cellulose or hydroxypropyl cellulose; Described pharmaceutic adjuvant is selected from one or more in filler, disintegrating agent, lubricant, binding agent, fluidizer.
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.
In described two-layer release-controlled tablet, 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:
Described two-layer release-controlled tablet, also comprises coatings, and described coatings comprises following component according to percentage by weight:
The preparation method of the class two-layer release-controlled tablet of sleeping peacefully of the present invention, is characterized in that, comprises the following steps:
1) will sleep peacefully class medicine and slow-release material and pharmaceutic adjuvant is mixed and made into slow-releasing granules; The class of sleeping peacefully 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.
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 20～30 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 of table 1 (1000, g)
Above-mentioned double-layer tablet can be used coating, and coatings contains following component:
| Hydroxypropyl methylcellulose 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 monohydrate 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. the alcoholic solution that compound concentration is 70% is to the soft material processed of the mixture in step 1;
3. the 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. the alcoholic solution that compound concentration is 80% is to the soft material processed of the mixture in step 1;
3. the 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-releasing granules is added to remaining silicon dioxide and magnesium stearate and be pressed into middle porose slow release layer, aperture is respectively 3mm, 4mm, 6mm; Also suppressed in addition the slow release layer that there is no hole;
2. slow releasing tablet is reentered in the punch die of tablet machine, filling immediate-release granules, rushes in row compacting for the second time by scrobicula, forms double-layer tablet;
3. the 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. the alcoholic solution that compound concentration is 75% is to the soft material processed of the mixture in step 1;
3. the 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. the alcoholic solution that compound concentration is 90% is to the soft material processed of the mixture in step 1;
3. the 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-releasing granules is added to remaining silicon dioxide and magnesium stearate and be pressed into middle porose slow release layer, aperture is respectively 4mm, 6mm;
2. slow release layer is reentered in the punch die of tablet machine, filling immediate-release granules, rushes in row compacting for the second time by scrobicula, forms double-layer tablet;
3. the 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, 0.25h sample detection, and release layer stripping, over 90%, 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. the alcoholic solution that compound concentration is 80% is to the soft material processed of the mixture in step 1;
3. the 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. the alcoholic solution that compound concentration is 90% is to the soft material processed of the mixture in step 1;
3. the 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-releasing granules is added to remaining silicon dioxide and magnesium stearate and be pressed into middle porose slow release layer, aperture is respectively 4mm, 6mm;
2. slow release layer is reentered in the punch die of tablet machine, filling immediate-release granules, rushes in row compacting for the second time by scrobicula, forms double-layer tablet;
3. the 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.
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. the alcoholic solution that compound concentration is 80% is to the soft material processed of the mixture in step 1;
3. the 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. the alcoholic solution that compound concentration is 90% is to the soft material processed of the mixture in step 1;
3. the 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-releasing granules is added to remaining silicon dioxide and magnesium stearate and be pressed into middle porose slow release layer, aperture is respectively 4mm, 6mm;
2. slow release layer is reentered in the punch die of tablet machine, filling immediate-release granules, rushes in row compacting for the second time by scrobicula, forms double-layer tablet;
3. the 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, 0.25h 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 17, 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. the class two-layer release-controlled tablet of sleeping peacefully, 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 sleep peacefully class medicine and pharmaceutic adjuvant, and described slow release layer is comprised of sleep peacefully 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, the described class medicine of sleeping peacefully is selected from zolpidem, Zaleplon, zopiclone, triazolam, midazolam, flurazepam, diazepam, chlordiazepoxide, nitrazepam, estazolam, alprazolam or lorazepam, or a kind of in the derivant of above-claimed cpd; Described slow-release material is selected from one or more in hydroxypropyl methylcellulose, ethyl cellulose or 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 class two-layer release-controlled tablet of sleeping peacefully of any one described in claim 1～6, is characterized in that, comprises the following steps:
1) will sleep peacefully class medicine and slow-release material and pharmaceutic adjuvant is mixed and made into slow-releasing granules; The class of sleeping peacefully 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. sleep peacefully the as described in claim 8 preparation method of class two-layer release-controlled tablet, is characterized in that, also comprises the step of coating.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310718529.2A CN103690505B (en) | 2013-12-23 | 2013-12-23 | A kind of sleeping class two-layer release-controlled tablet and preparation method thereof |
| PCT/CN2014/094367 WO2015096668A1 (en) | 2013-12-23 | 2014-12-19 | Double-layer tablet and preparation method 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 |
| DK14874251.3T DK3087980T3 (en) | 2013-12-23 | 2014-12-19 | DOUBLE LAYER TABLE AND METHOD OF PRODUCING THEREOF |
| ES14874251T ES2712129T3 (en) | 2013-12-23 | 2014-12-19 | Double-layer tablet and method of preparation |
| US16/178,543 US10940114B2 (en) | 2013-12-23 | 2018-11-01 | Hypnotics tablet with double-layer structure |
| US16/178,547 US10925836B2 (en) | 2013-12-23 | 2018-11-01 | Double-layer tablet and painkiller tablet with same structure |
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| WO2015096668A1 (en) * | 2013-12-23 | 2015-07-02 | 闻晓光 | Double-layer tablet and preparation method thereof |
| US10925836B2 (en) | 2013-12-23 | 2021-02-23 | Overseas Pharmaceuticals (Guangzhou) Ltd. | Double-layer tablet and painkiller tablet with same structure |
| US10940114B2 (en) | 2013-12-23 | 2021-03-09 | Overseas Pharmaceuticals (Guangzhou) Ltd. | Hypnotics tablet with double-layer structure |
| CN103932999A (en) * | 2014-04-14 | 2014-07-23 | 夏青 | Midazolam maleate dispersible tablet |
| CN112402389A (en) * | 2020-11-24 | 2021-02-26 | 常州欧法玛制药技术有限公司 | Zolpidem double-layer osmotic pump controlled release tablet and preparation method thereof |
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| CN103690505B (en) | 2016-01-20 |
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Effective date of registration: 20180823 Address after: 510000 self compiled A015 of A Building 5, No. 2, No. 2, No. Patentee after: Transoceanic pharmaceutical development (Guangzhou) Co., Ltd. Address before: 225300, 1 new drug development base, No. 1209, Yao Cheng Road, Taizhou, Jiangsu, 2 phase D building, room 1209. Patentee before: Wen Xiaoguang |