CN1765355A - Propafenone sustained release formulation and its preparation method - Google Patents
Propafenone sustained release formulation and its preparation method Download PDFInfo
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- CN1765355A CN1765355A CN 200410067664 CN200410067664A CN1765355A CN 1765355 A CN1765355 A CN 1765355A CN 200410067664 CN200410067664 CN 200410067664 CN 200410067664 A CN200410067664 A CN 200410067664A CN 1765355 A CN1765355 A CN 1765355A
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- propafenone
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- JWHAUXFOSRPERK-UHFFFAOYSA-N propafenone Chemical compound CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 JWHAUXFOSRPERK-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 56
- 229960000203 propafenone Drugs 0.000 title claims abstract description 56
- 239000000203 mixture Substances 0.000 title claims description 8
- 238000009472 formulation Methods 0.000 title claims description 4
- 238000013268 sustained release Methods 0.000 title description 2
- 239000012730 sustained-release form Substances 0.000 title description 2
- 239000011230 binding agent Substances 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 8
- 239000000463 material Substances 0.000 claims description 20
- 239000008187 granular material Substances 0.000 claims description 17
- 238000000576 coating method Methods 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 239000011248 coating agent Substances 0.000 claims description 12
- 239000007962 solid dispersion Substances 0.000 claims description 12
- 210000001072 colon Anatomy 0.000 claims description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- 229960002443 propafenone hydrochloride Drugs 0.000 claims description 6
- XWIHRGFIPXWGEF-UHFFFAOYSA-N propafenone hydrochloride Chemical compound Cl.CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 XWIHRGFIPXWGEF-UHFFFAOYSA-N 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 5
- -1 hydroxypropyl Chemical group 0.000 claims description 5
- 229920013820 alkyl cellulose Polymers 0.000 claims description 4
- 238000007796 conventional method Methods 0.000 claims description 4
- 229920001577 copolymer Polymers 0.000 claims description 4
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 claims description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 2
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- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 229940082484 carbomer-934 Drugs 0.000 claims description 2
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- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 2
- 229920003086 cellulose ether Polymers 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000003292 glue Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
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- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
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- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 238000012856 packing Methods 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims 1
- 229920000058 polyacrylate Polymers 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 abstract description 4
- 239000002270 dispersing agent Substances 0.000 abstract 1
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
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- 230000001225 therapeutic effect Effects 0.000 description 2
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- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a Propafenone slow release preparation and its preparing process, wherein the preparation comprises 10-76 wt% of Propafenone, 24-90% of solid dispersing agent, 1-20% of pH dependent binding agent and / or 1-10% of pH non-dependent binding agent.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to Propafenone slow releasing preparation and preparation method.
Background technology
The chemistry of Propafenone is called 3-phenyl-1-[2-[3-(third amino)-2 hydroxyls third amino] phenyl]-1-acetone, have following formula I structure:
Formula I
Its molecular formula is C
21H
27NO
3Propafenone hydrochloride is the Ic class anti-arrhythmic with local anesthesia effect, and its electric physiological effect has directly stablizes after birth effect and beta receptor blocking effect, and it can suppress fast Na
+Interior stream reduces the mutually maximum raising speed rate of O, and can suppress slow Ca
++Interior stream, the maximum climbing speed of reduction slow reacting cell, conduction velocity slows down.Clinical oral administration is widely used in artrial premature beat, ventricular premature contraction, preventative tachycardic outbreak.But the effect beginning in 0.5-1 hour of the oral back of this medicine reached the peak value of plasma concentration in 2-3 hour, and effect continues 4-8 hour.Therefore, the patient needed take medicine in per 6 hours 1 time, and also will get up and take medicine midnight, brought many inconvenience.
Summary of the invention
Technical problem to be solved by this invention is to adopt new preparation technique, provides take twice a kind of every day, makes the Propafenone slow releasing preparation of blood drug level stable maintenance in the valid density scope.
Propafenone is soluble,very slightly in water, the experiment proved that it mainly absorbs at stomach, and is difficult to absorb at intestinal wall.Propafenone is made the matrix tablet of pH dependent form, and this matrix tablet has good stripping curve (along with the extension of time, slowly stripping in the buffer of pH7.8) external, but almost nil when surveying intravital blood drug level.The medicine that stripping is described can not absorb for intestinal wall.Therefore by the preparation method of common slow releasing preparation, be difficult to obtain to absorb in vivo the good slow release preparation.For this reason, the inventor finds through research back repeatedly, when the active ingredient Propafenone in advance through the solid dispersion dispersion, the reuse macromolecular material is made slow releasing preparation, it is not only in small intestinal, colon stripping, and is absorbed, and has satisfied the treatment requirement.
Propafenone slow releasing preparation disclosed by the invention contains percentage by weight 10-76% Propafenone and 24-90% solid dispersion, preferably contains percentage by weight 10-60% Propafenone and 24-70% solid dispersion; Also can contain the non-pH dependency of 1-20%pH dependency binding agent and/or 1-10% binding agent simultaneously.
Slow releasing preparation of the present invention is oral granular formulation, capsule or tablet, and unit dose contains Propafenone 30-300mg.
In order to discern, hide flavor purpose and easy-to-swallow, also can be with Propafenone slow-releasing granules and the optional film former coating of slow releasing tablet.The amount of film former is the 2-15% of total formulation weight.Preferred hydroxypropyl emthylcellulose of film former and cation methacrylate copolymer.These film former also can comprise coloring agent, plasticizer or other adding ingredients.
Solid dispersion of the present invention is selected from one or more among Polyethylene Glycol, polyvinylpyrrolidone, Hydroxypropyl Methylcellulose Phathalate, cellulose acetate-phthalate, carboxymethylethylcellulose and the carbomer 934 P.
PH dependency binding agent of the present invention is selected from polyvinyl and copolymer, hydroxy alkyl cellulose, alkylcellulose, cellulose acetate, acetic acid hydroxy alkyl cellulose, cellulose ether, acetic acid alkylcellulose, and their ester.The preferable methyl acrylic copolymer.
Non-pH dependency binding agent of the present invention is selected from one or more in hydroxypropyl emthylcellulose, hydroxypropyl cellulose, methylcellulose, polyvinylpyrrolidone and neutral poly-(methyl) acrylate.
Another technical problem to be solved by this invention is to disclose the preparation method of above-mentioned Propafenone slow releasing preparation, and this method comprises the following steps:
1, solid dispersion is mixed with suitable quantity of water, heating is stirred, and makes its dissolving;
2, after the adding propafenone hydrochloride continues stirring and dissolving, put into refrigerator and cool off rapidly, solidify;
3, solidfied material is pulverized, sieved;
4, (1) solidfied material that step 3 is made and other pharmaceutic adjuvants and pH dependency binding agent or pH independent binder are mixed, and granulate with alcoholic solution, and drying is used the conventional method tabletting; Or
(2) solidfied material that step 3 is made is made granule with pH dependency binding agent or pH independent binder for the film former coating; Or
(3) solidfied material that step 3 is made is directly packed in the colon capsule.
When preparation of the present invention comprises pH dependency binding agent and non-pH dependency binding agent simultaneously, 4 (1) or 4 (2) method makes granule that contains pH dependency binding agent and the granule that contains non-pH dependency binding agent respectively set by step, with the weight ratio is the mixed of 0.5-1.5: 0.5-1.5, according to a conventional method in the tabletting or the glue shell of packing into.
Pharmaceutic adjuvant of the present invention is an adjuvant commonly used in the preparation.
When comprising pH dependency binding agent and non-pH dependency binding agent in the preparation of the present invention simultaneously, the may command Propafenone is dissolution rate in the aqueous medium of the pH scope of striding the harmonization of the stomach intestinal, Propafenone is slowly discharged in stomach, small intestinal and colon, thereby improve bioavailability and reduce toxic and side effects.
In the time of when preparation of the present invention is directly packed the colon capsule into simple non-pH-dependent sustained release dosage form (granulating or coating as Propafenone after solid dispersion is handled and non-pH dependency binding agent) or with the Propafenone after the solid dispersion processing in; can unite use with the Propafenone ordinary tablet, prolong and keep effective blood drug level.
The present invention handles Propafenone with solid dispersion earlier, adds the slow releasing preparation that macromolecular material is made again, absorption and uncorrelated in external stripping and the body, but can reach intravital absorption, have slow release effect.For arrhythmia, artrial premature beat, ventricular premature contraction, the patient of episode of tachycardia, in 24 hours with once or the frequency of secondary take the present invention and contain Propafenone 30-300mg preparation, kept the plasma concentration level and be more than the 100ng/ml 12-24 hour at least.Make the Propafenone plasma concentration near minimum effect level and with less peak valley fluctuation.Fig. 1 to Fig. 3 takes common Propafenone sheet blood drug level and time graph and the relation of taking slow release Propafenone preparation blood drug level of the present invention and time graph, therefrom as can be seen, take slow release Propafenone preparation of the present invention and can in 10-14 hour, keep comparatively stable blood drug level, and total blood drug level is apparently higher than common Propafenone sheet.
Propafenone slow releasing preparation of the present invention has overcome the shortcoming of existing ordinary tablet, makes things convenient for the patient on time, correctly take medicine, and has improved curative effect; Simultaneously steadily also making of blood drug level reduced side effect reaching under the situation of therapeutic effect.。
The invention will be further described below in conjunction with embodiment.
Description of drawings
Fig. 1 is for taking common Propafenone sheet blood drug level and time graph
Fig. 2 is for taking common Propafenone sheet and the Propafenone slow releasing preparation blood drug level and the time graph that do not contain pH dependency binding agent simultaneously
Fig. 3 is for taking slow release Propafenone preparation blood drug level and time graph
The specific embodiment
Embodiment 1
Taking polyethylene glycol 6000 (150g) is put into rustless steel container, is heated to 80 ℃ in water-bath, constantly stirs, and adds propafenone hydrochloride (60g) to complete after molten, and restir falls the people in refrigerator and cooled square position but immediately after 15 minutes, cooling rapidly.Take out after about 30 minutes.Get above-mentioned material and put into powder beater and beat powder, cross 40 mesh sieves, standby.
Get in microcrystalline Cellulose (50g), crospolyvinylpyrrolidone (5g), the above-mentioned material of magnesium stearate (2.4g) adding mix homogeneously in mixer-granulator.Granulate with the ethanol liquid that contains 1% polyvinylpyrrolidone, granule is dry on the fluid drying bed, sieves, and adds magnesium stearate (3g) mixing.Mixture is pressed into tablet, promptly.
Tablet is put into coating pan, does not stop to roll, and is heated to uniform temperature, sprays into the enteric material Germany You Teqi of Romo Co.,Ltd
R(acrylic copolymer class) coating, weightening finish 3-5%.Every contains Propafenone 89mg.
Embodiment 2
Get polyvinylpyrrolidone (150g) and put into rustless steel container, be heated to 80 ℃ in water-bath, constantly stir, add propafenone hydrochloride (100g) to complete after molten, restir falls the people in refrigerator and cooled square position but immediately after 15 minutes, cooling rapidly.Take out after about 30 minutes.Get above-mentioned material and put into powder beater and beat powder, cross 40 mesh sieves, standby.
Above-mentioned material is packed in the colon capsule promptly.Every contains Propafenone 89mg.
Embodiment 3
Get carbomer 934P (150g) and put into rustless steel container, be heated to 80 ℃ in water-bath, constantly stir, add propafenone hydrochloride (120g) to complete after molten, restir falls the people in refrigerator and cooled square position but immediately after 15 minutes, cooling rapidly.Take out after about 30 minutes.Get above-mentioned material and put into powder beater and beat powder, get the granule between 10 orders-20 order.
Above-mentioned granule in the air suspension fluidized bed, by the air that rises rapidly with granule in the indoor suspension fluidisation of coating, be in the flow regime of not stopping, coating solution is sprayed into the sulfuration bed, be wrapped in dosage surface.With acrylic resin is the coating material coating, weightening finish 8-13%, promptly.
Make the preparation that contains Propafenone 89mg.
Embodiment 4
Get carboxymethylethylcellulose (150g) and put into rustless steel container, in water-bath, be heated to 80 ℃, constantly stir, add propafenone hydrochloride (100g) after molten to complete, restir fall immediately after 15 minutes the people oneself in refrigerator and cooled square position but, cooling rapidly.Take out after about 30 minutes.Get above-mentioned material and put into powder beater and beat powder, get the granule between 10 orders-20 order.
Get above-mentioned particulate 50% by embodiment 3 method coatings, 50% granule is also operated by last method in addition, but coating material makes Ka Lekang (hydroxypropyl emthylcellulose) gastric solubleness material into.Two kinds of granules are by tabletting behind 1: 1 weight ratio mix homogeneously.
Every contains Propafenone 89mg.
Embodiment 5 ordinary preparations and Propafenone slow releasing preparation blood drug level are relatively
Take behind the common Propafenone sheet blood drug level and time graph and see Fig. 1, concrete data see Table 1.
After taking embodiment 1 Propafenone slow releasing preparation, clinical protocol is to add ordinary preparation again with this preparation when taking medicine first, makes blood drug level reach the peak rapidly, plays therapeutic effect; Under the situation of monitoring patient blood drug level, every day, secondary was taken this preparation, reached the purpose of keeping blood drug level then.Take blood drug level and the time graph that this preparation adds ordinary preparation again and see Fig. 2, concrete data see Table 2.
Take behind the embodiment 4 Propafenone slow releasing preparation blood drug level and time graph and see Fig. 3, concrete data see Table 3.
More than the amount of the Propafenone taken of 3 examples be 267mg.
Table 1
| Time (hr) | 5-OH PPF (ng/mL) | PPF (ng/mL) | Total concentration (ng/mL) |
| 0 1 2 3 4 5 6 8 10 14 24 36 | 0 68.4 99.6 130 103 72.8 46.5 32.7 24.7 12.6 3.28 0.533 | 0 174 306 366 331 242 145 91 47.6 10 0 0 | 0 242.4 405.6 496 434 314.8 191.5 123.7 72.3 22.6 3.28 0.533 |
| AUC 0-36(ug/L *h) 2841.83 | |||
Table 2
| Time (hr) | 5-OH PPF (ng/mL) | PPF (ng/mL) | Total concentration (ng/mL) |
| 0 1 2 3 4 5 6 8 10 14 24 36 | 0 39.8 69.8 70.4 70.9 61.5 61.6 51.2 34.3 23.8 12.1 3.06 | 0 167 345 469 356 280 273 161 84.4 40 10.3 0 | 0 206.8 414.8 539.4 426.9 341.5 334.6 212.2 118.7 63.8 22.4 3.06 |
| AUC 0-36(ug/L *h) 3923.160 | |||
Table 3
| Time (hr) | 5-OH PPF (ng/mL) | PPF (ng/mL) | Total concentration (ng/mL) |
| 0 1 2 3 4 5 6 8 10 14 24 36 | 0 32.6 41.9 36.5 47.8 50.2 54.9 49.6 39.3 39.2 12.7 7.13 | 0 173 250 185 185 177 178 149 118 86.6 13.3 2.61 | 0 205.6 291.9 221.5 232.8 227.2 232.9 198.6 157.3 125.8 26 9.74 |
| AUC 0-36(ug/L *h) 3148.121 | |||
In the last table: PPF represents Propafenone, and 5-OH PPF represents the metabolite of Propafenone.
Claims (10)
1, a kind of Propafenone slow releasing preparation is characterized in that it is 10-76% Propafenone and 24-90% solid dispersion that said preparation contains percentage by weight.
2, Propafenone slow releasing preparation according to claim 1 is characterized in that it is 10-60% Propafenone and 24-70% solid dispersion that said preparation contains percentage by weight.
3, Propafenone slow releasing preparation according to claim 1 and 2 is characterized in that also containing in the described slow releasing preparation 1-20%pH dependency binding agent and/or the non-pH dependency of 1-10% binding agent.
4, Propafenone slow releasing preparation according to claim 1 and 2 is characterized in that wherein said slow releasing preparation unit dose contains Propafenone 30-300mg.
5, Propafenone slow releasing preparation according to claim 1 and 2 is characterized in that wherein said slow releasing preparation adopts the film former coating, and the amount of film former is the 2-15% of total formulation weight.
6, Propafenone slow releasing preparation according to claim 1 and 2 is characterized in that wherein said solid dispersion is selected from one or more among Polyethylene Glycol, polyvinylpyrrolidone, Hydroxypropyl Methylcellulose Phathalate, cellulose acetate-phthalate, carboxymethylethylcellulose and the carbomer 934 P.
7, Propafenone slow releasing preparation according to claim 3, it is characterized in that wherein said pH dependency binding agent is selected from polyvinyl and copolymer, hydroxy alkyl cellulose, alkylcellulose, cellulose acetate, acetic acid hydroxy alkyl cellulose, cellulose ether, acetic acid alkylcellulose, and their ester; Non-pH dependency binding agent is selected from one or more in hydroxypropyl emthylcellulose, hydroxypropyl cellulose, methylcellulose, polyvinylpyrrolidone and the neutral polyacrylate.
8, Propafenone slow releasing preparation according to claim 5 is characterized in that wherein said film former is selected from hydroxypropyl emthylcellulose and cation methacrylate copolymer.
9, the preparation method of Propafenone slow releasing preparation according to claim 1 and 2 is characterized in that this method comprises the following steps:
A, solid dispersion is mixed with suitable quantity of water, heating is stirred, and makes its dissolving;
After b, adding propafenone hydrochloride continue stirring and dissolving, put into refrigerator and cool off rapidly, solidify;
C, solidfied material is pulverized, sieved;
The solidfied material that d, (1) make step c and pH dependency binding agent or non-pH dependency binding agent and other pharmaceutic adjuvants mix, and granulate with alcoholic solution, and drying is used the conventional method tabletting; Or
(2) solidfied material that step c is made is made the membrane coating with pH dependency binding agent or non-pH dependency binding agent and is made granule; Or
(3) solidfied material that step c is made is directly packed in the colon capsule.
10, the preparation method of Propafenone slow releasing preparation according to claim 9, it is characterized in that when comprising pH dependency binding agent and non-pH dependency binding agent in the preparation simultaneously, the method of d (1) or d (2) makes granule that contains pH dependency binding agent and the granule that contains non-pH dependency binding agent respectively set by step, with the weight ratio is the mixed of 0.5-1.5: 0.5-1.5, according to a conventional method in the tabletting or the glue shell of packing into.
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| CN 200410067664 CN1765355A (en) | 2004-10-29 | 2004-10-29 | Propafenone sustained release formulation and its preparation method |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102805738A (en) * | 2011-06-02 | 2012-12-05 | 天津药物研究院 | Propafenone hydrochloride sustained release preparation and preparation method |
| CN103432094A (en) * | 2013-09-11 | 2013-12-11 | 中国药科大学 | Propafenone hydrochloride sustained-release preparation and preparation method thereof |
| CN105902984A (en) * | 2016-05-29 | 2016-08-31 | 山东仁和堂药业有限公司 | Propafenone hydrochloride tablets and preparation method thereof |
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2004
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102805738A (en) * | 2011-06-02 | 2012-12-05 | 天津药物研究院 | Propafenone hydrochloride sustained release preparation and preparation method |
| CN102805738B (en) * | 2011-06-02 | 2014-04-16 | 天津药物研究院 | Propafenone hydrochloride sustained release preparation and preparation method |
| CN103432094A (en) * | 2013-09-11 | 2013-12-11 | 中国药科大学 | Propafenone hydrochloride sustained-release preparation and preparation method thereof |
| CN105902984A (en) * | 2016-05-29 | 2016-08-31 | 山东仁和堂药业有限公司 | Propafenone hydrochloride tablets and preparation method thereof |
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