CN102805738B - Propafenone hydrochloride sustained release preparation and preparation method - Google Patents
Propafenone hydrochloride sustained release preparation and preparation method Download PDFInfo
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- CN102805738B CN102805738B CN201110147169.6A CN201110147169A CN102805738B CN 102805738 B CN102805738 B CN 102805738B CN 201110147169 A CN201110147169 A CN 201110147169A CN 102805738 B CN102805738 B CN 102805738B
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- propafenone hydrochloride
- preparation
- propafenone
- hours
- releasing preparation
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- 229960002443 propafenone hydrochloride Drugs 0.000 title claims abstract description 42
- XWIHRGFIPXWGEF-UHFFFAOYSA-N propafenone hydrochloride Chemical compound Cl.CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 XWIHRGFIPXWGEF-UHFFFAOYSA-N 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 37
- 239000003405 delayed action preparation Substances 0.000 title abstract 4
- 239000008280 blood Substances 0.000 claims abstract description 5
- 210000004369 blood Anatomy 0.000 claims abstract description 5
- 229920002472 Starch Polymers 0.000 claims abstract description 3
- 239000008107 starch Substances 0.000 claims abstract description 3
- 235000019698 starch Nutrition 0.000 claims abstract description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract 3
- 229920000609 methyl cellulose Polymers 0.000 claims abstract 3
- 239000001923 methylcellulose Substances 0.000 claims abstract 3
- 235000010981 methylcellulose Nutrition 0.000 claims abstract 3
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract 3
- 229920000642 polymer Polymers 0.000 claims abstract 2
- 239000002671 adjuvant Substances 0.000 claims description 9
- 239000002775 capsule Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 239000007888 film coating Substances 0.000 claims description 3
- 238000009501 film coating Methods 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 238000007796 conventional method Methods 0.000 claims description 2
- 238000007873 sieving Methods 0.000 claims description 2
- 239000007779 soft material Substances 0.000 claims description 2
- 230000001186 cumulative effect Effects 0.000 claims 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims 1
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 1
- 238000011978 dissolution method Methods 0.000 claims 1
- 229960000203 propafenone Drugs 0.000 claims 1
- JWHAUXFOSRPERK-UHFFFAOYSA-N propafenone Chemical compound CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 JWHAUXFOSRPERK-UHFFFAOYSA-N 0.000 claims 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims 1
- 239000000314 lubricant Substances 0.000 abstract description 7
- 239000000945 filler Substances 0.000 abstract description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 abstract 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 abstract 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 abstract 1
- 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 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 235000015424 sodium Nutrition 0.000 abstract 1
- 238000013268 sustained release Methods 0.000 abstract 1
- 239000012730 sustained-release form Substances 0.000 abstract 1
- 239000000499 gel Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- -1 hydroxy-propyl Chemical group 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a propafenone hydrochloride sustained release preparation and a preparation method. The propafenone hydrochloride sustained release preparation comprises main components and a hydrophilic gel retardant such as one or more of polymer starch, methylcellulose, sodium methylcellulose, hydroxypropyl methyl cellulose and PEG (polyethylene glycol) which are 2:1-5:1 in weight percentage, and meanwhile comprises 3-10% of filler and appropriate amount of lubricant. According to the propafenone hydrochloride sustained release preparation and the preparation method, a hydrophilic gel sustained release technology is adopted to control the release speed of the propafenone hydrochloride so that blood concentration of the propafenone hydrochloride is maintained stable within 12 hours.
Description
Technical field
The invention belongs to medical technical field, be specifically related to propafenone hydrochloride oral slow-releasing preparation and preparation method thereof.
Background technology
Propafenone hydrochloride (C
21h
27nO
3hCl) be the Ic class anti-arrhythmic with local anesthesia effect, its electric physiological effect has direct stabilized cell membrane interaction 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, reduce the maximum climbing speed of slow reacting cell, conduction velocity slows down.Conventional oral ordinary preparation clinically, starts effect for 0.5～1 hour after taking, and within 2～3 hours, reaches peak plasma concentration, and effect continues 4～8 hours.Therefore patient need frequently take medicine, and will bring like this inconvenience.The propafenone hydrochloride slow releasing capsule (12 hours slow release) of U.S. Abbott development and production is that the micro chip of 2 × 2mm incapsulates, in-built approximately 50～60 micro chips of every capsules, and domestic production equipment almost can not reach this requirement at present.
Summary of the invention
The object of the invention is to overcome the shortcoming and defect of above-mentioned prior art, a kind of propafenone hydrochloride oral slow-releasing preparation is provided, what described propafenone hydrochloride slow releasing preparation adopted is hydrophilic gel slow release method, with propafenone hydrochloride and hydrophilic gel blocker, weight ratio is 2: 1～5: 1, contain simultaneously 3%～10% filler and suitable lubricant through mixing, granulate, dry, tabletting and get final product.This product has release profiles in the body similar to the propafenone hydrochloride slow releasing capsule of U.S. Abbott development and production, and said preparation is suitable for twice administration in oral a day, and said preparation is taken rear average peak reaching time of blood concentration (T
max) be 4～6 hours, the oral effect that reached even release after once in 12 hours, and preparation technology is simple, is easy to industrialization, and cost is low.
Propafenone hydrochloride slow releasing preparation of the present invention is made by following component:
Propafenone hydrochloride (C
21h
27nO
3hCl);
Hydrophilic gel blocker;
Filler, lubricant.
Wherein the weight ratio of propafenone hydrochloride and hydrophilic gel blocker is 2: 1～5: 1.
By mixed propafenone hydrochloride, with hydrophilic blocker, then this mixture is prepared into solid dosage, as tablet or capsule.When such preparation contacts with water, form a kind of swell gel substrate, medicine slowly releases from this substrate.
Propafenone hydrochloride crude drug involved in the present invention is comparatively loose, so add the adjuvant that improves tablet compressibility in prescription, can select cellulose family and starch based, as one or more mixing in lactose, microcrystalline Cellulose, low substituted hydroxy-propyl fiber, mannitol are used as filler, improve compressibility.Can select stearic acid, magnesium stearate on the one hand as lubricant, because it has stronger hydrophobicity, play certain retardation on the other hand.Can select micropowder silica gel, Pulvis Talci etc. to increase mobility of particle.
Propafenone hydrochloride is slightly soluble in water, therefore according to this characteristic, adopts suitable hydrophilic gel substrate, and assistant, with suitable filler and lubricant, is prepared into 12 hours slow releasing preparation.
The weight ratio that propafenone hydrochloride slow releasing preparation disclosed by the invention contains propafenone hydrochloride and hydrophilic gel blocker is 2: 1～5: 1, contains 3%～10% filler and suitable lubricant simultaneously.
Slow releasing preparation of the present invention can be sustained release tablet for oral use or capsule, and it is 225～325mg that unit dose contains propafenone hydrochloride.
Technical problem to be solved by this invention is the openly preparation method of above-mentioned propafenone hydrochloride slow releasing preparation, and the method comprises the following steps:
A, first by raw material propafenone hydrochloride and each adjuvant sieving for standby respectively;
B, according to recipe quantity, take each adjuvant, soft material processed, pelletize after mix homogeneously, dry, with conventional method tabletting or encapsulated;
C, film coating.
Adjuvant described in the present invention is conventional adjuvant in preparation.Propafenone hydrochloride slow releasing preparation of the present invention has overcome the shortcoming of existing ordinary preparation, facilitates patient to take medicine on time, and improves curative effect, and treatment specific aim is stronger, simultaneously the generation that steadily also makes to greatly reduce side effect in treatment of blood drug level.
Technical problem to be solved by this invention is to adopt simple preparation technique, prepare the propafenone hydrochloride hydrophilic gel slow releasing preparation of taking twice a kind of every day, said preparation shows reproducible high trap and uniform plasma concentration in during 12 hours after administration, makes recurrent atrial fibrillation be able to steady control.Said preparation shows by zoopery, has release profiles (seeing Fig. 3) in the body similar to the propafenone hydrochloride slow releasing capsule of U.S. Abbott development and production.And preparation technology is simple, be easy to industrialization, cost is low.
Accompanying drawing explanation
Fig. 1 is the release in vitro curve of propafenone hydrochloride slow releasing tablet (225mg)
Fig. 2 is the release in vitro curve of propafenone hydrochloride slow releasing tablet (325mg)
Fig. 3 is blood drug level-time graph in slow releasing capsule (325mg, R) the single-dose body of propafenone hydrochloride slow releasing tablet (325mg, T) and the development and production of U.S. Abbott in embodiment
The specific embodiment
By various preparation prescriptions, describe different embodiments in detail below, only conduct explanation of these embodiment, and the present invention is not produced to any restriction.
Embodiment 1
Embodiment 4
According to the compositions of the embodiment of the present invention, make every containing 225 milligrams or 325 milligrams of propafenone hydrochloride slow releasing preparation, concrete preparation method is as follows:
A, raw material propafenone hydrochloride and adjuvant is standby by 100 sieves, 80 mesh sieves respectively;
B, according to recipe quantity, take each adjuvant, after mix homogeneously, mix all with equivalent incremental method with propafenone hydrochloride;
C, add appropriate wetting agent to mix after, with 14 mesh sieve pelletizes, and in 60 ℃ of oven for baking to dry;
D, collect granule, according to 0.5% of granule gross weight, add lubricant, measure intermediate content, determine single dose weight, tabletting or encapsulated;
E, film coating, weightening finish 2～3%.
The release in vitro curve of embodiment propafenone hydrochloride slow releasing tablet is shown in Fig. 1～Fig. 2.
Claims (3)
1. an oral slow-releasing preparation for propafenone hydrochloride, is characterized in that, comprises propafenone hydrochloride and hydrophilic gel blocker; Described hydrophilic gel blocker can be one or more in polymer starch, methylcellulose, sodium carboxymethyl cellulose, Polyethylene Glycol; The hydrochloric Propafenone of described unit dose is 225～325mg; The weight ratio of described propafenone hydrochloride and hydrophilic gel blocker is 2:1～5:1; After described propafenone hydrochloride slow releasing preparation administration, average peak reaching time of blood concentration is 4～6 hours; According to dissolution method, cumulative release amount is total amount in its 2 hours 20%～35%, and in its 4 hours, cumulative release amount is total amount 45%～65%, and in its 8 hours, cumulative release amount is total amount 80%～100%.
2. the oral slow-releasing preparation of propafenone hydrochloride according to claim 1, is characterized in that, the concrete form of slow releasing preparation is tablet, capsule.
3. the method for the propafenone hydrochloride oral slow-releasing preparation described in preparation claim 1～2 any one, is characterized in that, the method comprises the following step:
A, first by raw material propafenone hydrochloride and each adjuvant sieving for standby respectively;
B, according to recipe quantity, take soft material processed after each adjuvant mix homogeneously, pelletize, dry, with conventional method tabletting or encapsulated;
C, film coating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110147169.6A CN102805738B (en) | 2011-06-02 | 2011-06-02 | Propafenone hydrochloride sustained release preparation and preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110147169.6A CN102805738B (en) | 2011-06-02 | 2011-06-02 | Propafenone hydrochloride sustained release preparation and preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102805738A CN102805738A (en) | 2012-12-05 |
| CN102805738B true CN102805738B (en) | 2014-04-16 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103432094A (en) * | 2013-09-11 | 2013-12-11 | 中国药科大学 | Propafenone hydrochloride sustained-release preparation and preparation method thereof |
| CN117462502B (en) * | 2023-10-26 | 2024-06-11 | 山东丰金生物医药有限公司 | Propafenone hydrochloride sustained-release composition and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1765355A (en) * | 2004-10-29 | 2006-05-03 | 上海市徐汇区中心医院 | Propafenone sustained release formulation and its preparation method |
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2011
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1765355A (en) * | 2004-10-29 | 2006-05-03 | 上海市徐汇区中心医院 | Propafenone sustained release formulation and its preparation method |
Non-Patent Citations (2)
| Title |
|---|
| 张娜等.盐酸普罗帕酮缓释片的研制.《山东大学学报(医学版)》.2003,第41卷(第2期), |
| 盐酸普罗帕酮缓释片的研制;张娜等;《山东大学学报(医学版)》;20030430;第41卷(第2期);第203-205,208页 * |
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| Publication number | Publication date |
|---|---|
| CN102805738A (en) | 2012-12-05 |
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Address after: 300193 Tianjin City, Nankai District Anshan West Road No. 308 Patentee after: TIANJIN INSTITUTE OF PHARMACEUTICAL RESEARCH CO., LTD. Address before: 300193 Tianjin City, Nankai District Anshan West Road No. 308 Patentee before: Tianjin Institute of Pharmaceutical Research |
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Granted publication date: 20140416 Termination date: 20210602 |