CN103054820A - Dronedarone hydrochloride pharmaceutical composition and preparation method thereof - Google Patents
Dronedarone hydrochloride pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN103054820A CN103054820A CN2012103027933A CN201210302793A CN103054820A CN 103054820 A CN103054820 A CN 103054820A CN 2012103027933 A CN2012103027933 A CN 2012103027933A CN 201210302793 A CN201210302793 A CN 201210302793A CN 103054820 A CN103054820 A CN 103054820A
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Abstract
The invention provides a dronedarone hydrochloride pharmaceutical composition which is suitable for the sublingual administration, can quickly run, and can greatly improve the bioavailability and the curative effect. The pharmaceutical composition consists of 5-65 parts of dronedarone hydrochloride, 1-10 parts of a disintegrating agent, 10-80 parts of filler, 0.5-3 parts of antacid, 0-5 parts of corrigent, 1-10 parts of an adhesive and 0.3-2 parts of a lubricating agent. The invention further provides a preparation method suitable for the industrial production. The dronedarone hydrochloride pharmaceutical composition provided by the invention is directly absorbed by the sublingual mucosa, and the first-pass effect of oral medicaments can be avoided, and the gastrointestinal digestion, acidolysis and the like can be avoided, so that the bioavailability can be greatly improved. The epithelium of the sublingual mucosa is not cornified, so that the dronedarone hydrochloride pharmaceutical composition is large in superficial area, and high in infiltration capacity. The medicament can be quickly absorbed after being administrated, so that the dronedarone hydrochloride pharmaceutical composition is quick to run, and convenient to use; and compared with the other administrated preparations, the dronedarone hydrochloride pharmaceutical composition is convenient to administrate, and good in patient compliance.
Description
Technical field
The invention belongs to field of medicaments, particularly a kind of dronedarone hydrochloride pharmaceutical composition and preparation method.
Background technology
Dronedarone (Dronedarone) chemistry N-[2-butyl-3-[4-[3-(dibutylamino) propoxyl group by name] benzoyl]-the 5-benzofuranyl] the Methanesulfomide benzofuran, molecular formula C
31H
44N
2O
5S, molecular weight 593.22. chemical formula is as follows:
Dronedarone hydrochloride is the treatment antiarrhythmic medicament by the Sanofi-Aventis exploitation.This product is not for containing the benzofuran derivative of iodine, and Structure and characteristics and iodine amine ketone seemingly but do not contain iodine, and lipotropy is low, takes rear phospholipid and can not be deposited on pulmonary, so cardiovascular system untoward reaction is outward lacked than iodine amine ketone, clinical tolerance is good.This product half-life is 1-2 days, is more conducive to adjust drug dose.
Dronedarone hydrochloride dissolubility in water-bearing media is very low, and particularly its dissolubility at room temperature becomes the pH value dependency.Maximum dissolubility is arranged in pH value 3-5 scope, be about 1-2mg/ml, when the dissolution medium of pH1.0, pH2.0, dissolve hardly, the 10-30 μ g/ml that only has an appointment, the dissolubility under pH7.0 only has 10 μ g/ml.Because this characteristic, cause the bioavailability of its gastrointestinal administration low, although because medicine dissolubility under one's belt is better, entering can't stripping from solid preparation behind the intestinal.For improving the bioavailability of dronedarone hydrochloride, must find the approach that can improve its dissolution.
WO9858643 discloses a kind of solid composite medicament that contains benzofuran derivatives, it finds poloxamer class nonionic surfactant and dronedarone or its hydrochlorate, this active component is kept among the pH neutral 6-7 and can not separate out precipitation, improve the bioavailability of dronedarone hydrochloride.
CN101152154A discloses a kind of solid composite medicament, wherein contains micronized dronedarone hydrochloride, surfactant (sodium lauryl sulfate) and as the hydrophilic polymer of cosolvent.
CN101039657A discloses a kind of pharmaceutical composition that contains solid dispersion, this dispersion contains at least a active main constituent and contains (i) and (ii) mixture at pharmaceutically acceptable polymeric matrix: (i) be the mutually polydextrose of form of continuous polydextrose, (ii) the polymer of at least a continuous phase form that is this polymer except polydextrose.
The CN102188417A invention relates to dronedarone medicinal composition, it is characterized in that it contains is used for the treatment of ARR dronedarone or its pharmaceutically acceptable salt as active component, a kind of pharmaceutically acceptable amphipathic lipids surfactant and phospholipid, optionally is combined with one or more medicated premixs.
A kind of dronedarone hydrochloride pharmaceutical composition is disclosed among the CN102078307A, this product is dispersible tablet, said preparation is the tablet made from adjuvant again after the dronedarone hydrochloride solid dispersion technology micronization processes, this product has been improved the dissolubility of principal agent, promote the quick disintegrate of medicine, with the absorbability that advances to have increased in blood, improved the bioavailability of principal agent.
Medicine exists with solid form in gastrointestinal tract, and dissolubility is low, and just can not well be absorbed by the body enters blood, thereby makes bioavailability low, does not reach curative effect.
Above technology all is in order to increase the dissolubility of dronedarone, and studies show that dronedarone is oral well to be absorbed.Be what its blood plasma peak time of species between the 1-4 behind the oral drugs hour no matter affect the main cause of bioavailability, in case be absorbed, dronedarone can experience a first pass effect, thereby causes its absolute bioavailability low at all.Therefore the gastrointestinal administration mode all can not solve the low problem of oral bioavailability rate at all, can address this problem and be developed to the parenteral administration.
First pass effect refers to some drugs through gastrointestinal administration, not yet absorb enter blood circulation before, by metabolism, and the phenomenon that the original shape dose that enters blood circulation is reduced also claims the first pass effect at intestinal mucosa and liver.After standing the deactivation metabolism by intestinal mucosa and liver, the dose that enters the body circulation reduced, drug effect reduces effect after some drugs was oral.The phenomenons that drug influence created a difference because route of administration is different are significant on therapeutics.
The intestinal external administration can be avoided first-pass effect such as injection, subcutaneous or sublingual administration.
US20040044070 discloses the injection of dronedarone hydrochloride.This invention has added beta-cyclodextrin derivative in buffer system (PH3-5), improved the dissolubility of effective ingredient from face.But the method for this raising dronedarone hydrochloride dissolubility, complicate fabrication process, cost height and less stable.
Summary of the invention
For the deficiency that prior art exists, the object of the present invention is to provide a kind of sublingual administration that is suitable for, rapidly onset significantly improves the dronedarone hydrochloride pharmaceutical composition of bioavailability and curative effect.
Dronedarone hydrochloride pharmaceutical composition of the present invention is prepared from by dronedarone hydrochloride 5-65 part, disintegrating agent 1-10 part, filler 10-80 part, correctives 0.5-5 part, binding agent 1-10 part and lubricant 0.3-2 part.
Preferred version is: described pharmaceutical composition is prepared from by dronedarone hydrochloride 5-65 part, disintegrating agent 1-10 part, filler 10-80 part, antacid 0.5-3 part, correctives 0.5-5 part, binding agent 1-10 part, lubricant 0.3-2 part.
More preferably scheme is: described pharmaceutical composition is prepared from by dronedarone hydrochloride 20-50 part, disintegrating agent 1-5 part, filler 30-55 part, antacid 1.5-2.5 part, correctives 1-3 part, binding agent 1-6 part and lubricant 0.3-1 part.
Most preferably scheme is: described pharmaceutical composition is prepared from by dronedarone hydrochloride 38-40 part, disintegrating agent 2-5 part, filler 40-45 part, 2 parts of antacids, correctives 1.5-2 part, binding agent 4-5 part and lubricant 0.5-0.8 part.
Among the present invention, any one or more mixture in described disintegrating agent preferably microcrystalline cellulose, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, carboxymethyl starch sodium, low-substituted hydroxypropyl methylcellulose, starch, tween, the sodium lauryl sulphate.
Any one or more mixture in described filler preferably microcrystalline cellulose, microcrystalline Cellulose-mannitol, microcrystalline Cellulose-micropowder silica gel, lactose, starch, modified starch-1500, mannitol, sorbitol, xylitol, erythrose, pregelatinized Starch, Icing Sugar, glucose, dextrin, the calcium sulfate.
Described antacid comprises any inorganic or organic acid, exists with the form of free acid, anhydride or hydrochlorate.Preferably citric acid, ascorbic acid, lactic acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, glycolic acid, aminoacid, and derivant etc.The present inventor is surprised to find that, adds antacid in prescription, can effectively improve the absorption of dronedarone hydrochloride sublingual administration, thereby improves bioavailability.
Any one or more mixture of the preferred stevioside of described correctives, Icing Sugar, Liquoride sugar element, Aspartane, sucralose, cyclamate, Talin, glucide.
Any one or more mixture in the preferred purified water of described binding agent, ethanol, starch slurry, hydroxypropyl first methylcellulose, polyvinylpyrrolidone, carbomer, dextrin, gelatine size, mucialga of arabic gummy, sodium alginate and the syrup.
Any one or more mixture in the preferred stearic acid of described lubricant, magnesium stearate, calcium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycol 6000, Macrogol 4000, sodium lauryl sulphate, the fumaric acid sodium stearate;
A kind of dronedarone hydrochloride pharmaceutical composition provided by the invention is preferably by the administration of sublingual administration mode.Dronedarone hydrochloride pharmaceutical composition provided by the invention by the sublingual administration mode, without first pass effect, has improved bioavailability and the curative effect of medicine; The effect of having immediate effect can discharge rapidly active component soon its absorption of existing side by side.
Dronedarone hydrochloride pharmaceutical composition provided by the invention (sublingual administration), through carrying out the interior bioavailability of body relatively with the former producer's listing product dronedarone hydrochloride sheet (Oral Gastrointestinal Tract absorption) that grinds, pharmaceutical composition dosage of the present invention is significantly less than the listing tablet, and bioavailability and listing product are quite or be better than the product that goes on the market.
The present invention provides a kind of preparation method of dronedarone hydrochloride pharmaceutical composition simultaneously, so that the smooth suitability for industrialized production of dronedarone hydrochloride pharmaceutical composition sheet of the present invention.
It is characterized in that comprising the steps:
(1) binding agent and antacid are dissolved in prepare binder solution in the suitable quantity of water;
(2) principal agent dronedarone hydrochloride, filler, disintegrating agent, correctives, lubricant are carried out drying, the pretreatment of sieving;
(3) with pretreated principal agent, filler, disintegrating agent, correctives mix homogeneously;
(4) binder solution is added in the above-mentioned material of mixing, make soft material, granulate 40-60 ℃ of drying;
(5) add the lubricant mixing in the dried granule, tabletting gets finished product again.
Preferred version is: sieve in the described step (2) as passing through 60 mesh sieves; Baking temperature is 50 ℃ in the step (4).
Dronedarone hydrochloride pharmaceutical composition provided by the invention is not limited to adopt above preparation method preparation; for example; after in binding agent and the antacid one or both are sieved; can directly mix with other supplementary material; water is granulated as wetting agent, need not prepare binder solution, in addition; in the above-mentioned preparation method, method of granulating can also adopt the mode of dry granulation or fluidized bed granulation.Dronedarone hydrochloride pharmaceutical composition of the present invention can also be realized by direct powder compression or compressing dry granulation, also can first dronedarone hydrochloride be prepared into solid dispersion or clathrate, be prepared into again the dronedarone hydrochloride pharmaceutical composition of sublingual absorption.
Dronedarone hydrochloride pharmaceutical composition of the present invention is directly absorbed by hypoglossis mucous membrane, has avoided the first pass effect of oral drugs, has avoided gastrointestinal tract enzymolysis, acidolysis etc., and bioavailability is improved greatly.And the hypoglossis mucous membrane epithelium is keratinization not, and surface area is large, and penetrating power is strong.Hypoglossis mucous membrane has a large amount of blood capillaries to gather to internal jugular vein, directly enters blood circulation through superior vena cava, and medicine absorbs rapidly after the administration, and onset is rapid, easy to use.And than other non-oral Preparation convenient drug administration, patient compliance is good.
Description of drawings
Fig. 1 the present invention makes product and listing ordinary tablet
Blood drug level-time plot
Wherein, 1 is ordinary tablet, and 2 is to be the product that the present invention obtains.
The specific embodiment
Following embodiment is all in 1000 amount.
Embodiment 1:
Preparation prescription: dronedarone hydrochloride 5g, lactose 40g, mannitol 40g, crospolyvinylpyrrolidone 5g, lactic acid 0.5g, stevioside 5g, Macrogol 4000 lg, polyvinylpyrrolidone 2g.
Concrete preparation method is as follows: with principal agent, and the pretreatment of drying, pulverize, sieve of filler lactose, mannitol, disintegrating agent crospolyvinylpyrrolidone, correctives steviol glycosides and lubricant Macrogol 4000; Polyvinyl pyrrolidone and antacid lactic acid dissolution are made binder solution in suitable quantity of water; With pretreated principal agent and filler, correctives and disintegrating agent mixing, use the binder solution soft material processed for preparing, 20 mesh sieves are granulated; Under 40 ℃ of temperature, be dried to and meet moisture≤2%; Lubricant is added in the dried granule of gained, always mix, last tabletting gets the dronedarone hydrochloride Sublingual tablet.
Embodiment 2:
Preparation prescription: dronedarone hydrochloride 40g, microcrystalline Cellulose-mannitol 40g, crospolyvinylpyrrolidone 5g, citric acid 2g, stevioside 2g, Macrogol 4000 0.5g, polyvinylpyrrolidone 5g.
Concrete preparation method is as follows: with principal agent, fill microcrystalline Cellulose-mannitol, the pretreatment of drying, pulverize, sieve of disintegrating agent crospolyvinylpyrrolidone, correctives steviol glycosides and lubricant Macrogol 4000; Polyvinyl pyrrolidone and antacid citric acid be dissolved in make binder solution in the suitable quantity of water; With pretreated principal agent and filler, correctives and disintegrating agent mixing, use the binder solution soft material processed for preparing, 20 mesh sieves are granulated; Under 50 ℃ of temperature, be dried to and meet moisture≤2%; Lubricant is added in the dried granule of gained, always mix, last tabletting gets the dronedarone hydrochloride Sublingual tablet.Make product and listing ordinary tablet
Blood drug level-time graph is seen Fig. 1.
Embodiment: 3:
Preparation prescription: dronedarone hydrochloride 65g, Icing Sugar 10g, mannitol 30g, carboxymethyl starch sodium 10g, citric acid 3g, stevioside 3g, magnesium stearate 2g, polyvinylpyrrolidone 3g.
Concrete preparation method is as follows: with principal agent, and the pretreatment of drying, pulverize, sieve of filler Icing Sugar, mannitol, carboxymethyl starch sodium, correctives steviol glycosides and magnesium stearate lubricant; Polyvinyl pyrrolidone and antacid citric acid be dissolved in prepare binder solution in the suitable quantity of water; With pretreated principal agent and filler, correctives and disintegrating agent mixing, use the binder solution soft material processed for preparing, 20 mesh sieves are granulated; Under 60 ℃ of temperature, be dried to and meet moisture≤2%; Lubricant is added in the dried granule of gained, always mix, last tabletting gets the dronedarone hydrochloride Sublingual tablet.
Embodiment 4:
Preparation prescription: dronedarone hydrochloride 20g, microcrystalline Cellulose-mannitol 30g, crospolyvinylpyrrolidone lg, citric acid 1.5g, stevioside 1g, Macrogol 4000 0.3g, polyvinylpyrrolidone 1g.
Concrete preparation method is as follows: with principal agent, and the pretreatment of drying, pulverize, sieve of filler Icing Sugar, mannitol, carboxymethyl starch sodium, correctives steviol glycosides and magnesium stearate lubricant; Polyvinyl pyrrolidone and antacid citric acid be dissolved in prepare binder solution in the suitable quantity of water; With pretreated principal agent and filler, correctives and disintegrating agent mixing, use the binder solution soft material processed for preparing, 20 mesh sieves are granulated; Under 60 ℃ of temperature, be dried to and meet moisture≤2%; Lubricant is added in the dried granule of gained, always mix, last tabletting gets the dronedarone hydrochloride Sublingual tablet.
Embodiment 5:
Preparation prescription: dronedarone hydrochloride 50g, microcrystalline Cellulose-mannitol 55g, crospolyvinylpyrrolidone 5g, citric acid 2.5g, stevioside 3g, Macrogol 4000 1g, polyvinylpyrrolidone 6g.
Concrete preparation method is as follows: with principal agent, and the pretreatment of drying, pulverize, sieve of filler Icing Sugar, mannitol, carboxymethyl starch sodium, correctives steviol glycosides and magnesium stearate lubricant; Polyvinyl pyrrolidone and antacid citric acid be dissolved in prepare binder solution in the suitable quantity of water; With pretreated principal agent and filler, correctives and disintegrating agent mixing, use the binder solution soft material processed for preparing, 20 mesh sieves are granulated; Under 60 ℃ of temperature, be dried to and meet moisture≤2%; Lubricant is added in the dried granule of gained, always mix, last tabletting gets the dronedarone hydrochloride Sublingual tablet.
Embodiment 6:
Preparation prescription: dronedarone hydrochloride 38g, microcrystalline Cellulose-mannitol 45g, crospolyvinylpyrrolidone 2g, citric acid 2g, stevioside 1.5g, Macrogol 4000 0.8g, polyvinylpyrrolidone 4g.
Concrete preparation method is as follows: with principal agent, and the pretreatment of drying, pulverize, sieve of filler Icing Sugar, mannitol, carboxymethyl starch sodium, correctives steviol glycosides and magnesium stearate lubricant; Polyvinyl pyrrolidone and antacid citric acid be dissolved in prepare binder solution in the suitable quantity of water; With pretreated principal agent and filler, correctives and disintegrating agent mixing, use the binder solution soft material processed for preparing, 20 mesh sieves are granulated; Under 60 ℃ of temperature, be dried to and meet moisture≤2%; Lubricant is added in the dried granule of gained, always mix, last tabletting gets the dronedarone hydrochloride Sublingual tablet.
Embodiment 7:
Bioavailability test in the body: intersect the comparative study of single dose relative bioavailability according to embodiment 2 gained Sublingual tablets (40mg) and ordinary tablet (400mg), the Beagle dog of empty stomach is as laboratory animal after the fasting.
This experimentation purpose for the oral formulations of estimating two kinds of different way of administration to fasting after on an empty stomach the relative bioavailability of single dose administration of Beagle dog, illustrate that medicine is behind sublingual administration, effectively avoid the first pass effect of dronedarone, significantly improved the bioavailability of medicine.
According to the tablet of embodiment 2 preparations and with reference to 6 Beagle of product difference administration, measure the pharmacokinetic parameters such as Cmax, Tmax, AUC.
The reference product are dronedarone sheets that Sanofi-Aventis company produces, trade mark
Listing in the world wide.
The present invention and reference product all contain dronedarone (hydrochloride form), but the present invention contains the dronedarone that medicine is 40mg, and contain the dronedarone that medicine is 400mg with reference to product.
The blood sampling time: take a sample with reference to the following time before the administration and after the administration.
The Sublingual tablet blood sampling time: before the administration and after the administration 0.17,0.33,0.5,0.75,1,1.5,2,3,4,6,8,12,24,36,48h.
With reference to the product blood sampling time: before the administration with administration after 0.5,1,2,3,4,5,6,7,8,12,24,36,48h.
The main pharmacokinetic parameter such as AUC0-t, AUC0-∞, Tmax, Cmax calculates according to dronedarone in the blood plasma.
The result is as shown in table 1:
Table 1 blood drug level-time graph
Product of the present invention and reference product
Average ratio as shown in table 2:
Table 2 relative bioavailability
The result also provides in Fig. 1 simultaneously.
Studies show that: product of the present invention is to similar with Cmax with reference to the bioavailability of product, and relative bioavailability is greater than 90%, bioequivalence.
Illustrate that dronedarone hydrochloride pharmaceutical composition of the present invention can reach the drug effect suitable with the listing product through sublingual administration with smaller dose.
Above embodiment, in order to limit the present invention, within the spirit and principles in the present invention not all only for the purpose of description, any modification of doing, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (14)
1. a dronedarone hydrochloride pharmaceutical composition is characterized in that described pharmaceutical composition is prepared from by dronedarone hydrochloride 5-65 part, disintegrating agent 1-10 part, filler 10-80 part, correctives 0.5-5 part, binding agent 1-10 part and lubricant 0.3-2 part.
2. a kind of dronedarone hydrochloride pharmaceutical composition according to claim 1 is characterized in that described pharmaceutical composition is prepared from by dronedarone hydrochloride 5-65 part, disintegrating agent 1-10 part, filler 10-80 part, antacid 0.5-3 part, correctives 0.5-5 part, binding agent 1-10 part, lubricant 0.3-2 part.
3. a kind of dronedarone hydrochloride pharmaceutical composition according to claim 2 is characterized in that described pharmaceutical composition is prepared from by dronedarone hydrochloride 20-50 part, disintegrating agent 1-5 part, filler 30-55 part, antacid 1.5-2.5 part, correctives 1-3 part, binding agent 1-6 part and lubricant 0.3-1 part.
4. a kind of dronedarone hydrochloride pharmaceutical composition according to claim 3 is characterized in that described pharmaceutical composition is prepared from by dronedarone hydrochloride 38-40 part, disintegrating agent 2-5 part, filler 40-45 part, 2 parts of antacids, correctives 1.5-2 part, binding agent 4-5 part and lubricant 0.5-0.8 part.
5. described a kind of dronedarone hydrochloride pharmaceutical composition is characterized in that described disintegrating agent is selected from any one or more mixture in microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, carboxymethyl starch sodium, low-substituted hydroxypropyl methylcellulose, starch, tween, the sodium lauryl sulphate according to claim 1-4.
6. described a kind of dronedarone hydrochloride pharmaceutical composition is characterized in that described filler is selected from any one or more mixture in microcrystalline Cellulose, microcrystalline Cellulose-mannitol, microcrystalline Cellulose-micropowder silica gel, lactose, starch, modified starch-1500, mannitol, sorbitol, xylitol, erythrose, pregelatinized Starch, Icing Sugar, glucose, dextrin, the calcium sulfate according to claim 1-4.
7. described a kind of dronedarone hydrochloride pharmaceutical composition is characterized in that described antacid comprises any inorganic or organic acid according to claim 1-4, exists with the form of free acid, anhydride or hydrochlorate.
8. a kind of dronedarone hydrochloride pharmaceutical composition according to claim 7, it is characterized in that described antacid is selected from citric acid, ascorbic acid, lactic acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, glycolic acid, aminoacid, and derivant.
9. described a kind of dronedarone hydrochloride pharmaceutical composition is characterized in that described correctives is selected from any one or more mixture of stevioside, Icing Sugar, Liquoride sugar element, Aspartane, sucralose, cyclamate, Talin, glucide according to claim 1-4.
10. described a kind of dronedarone hydrochloride pharmaceutical composition is characterized in that described binding agent is selected from any one or more mixture in purified water, ethanol, starch slurry, hydroxypropyl first methylcellulose, polyvinylpyrrolidone, carbomer, dextrin, gelatine size, mucialga of arabic gummy, sodium alginate and the syrup according to claim 1-4.
11. described a kind of dronedarone hydrochloride pharmaceutical composition is characterized in that described disintegrating agent is selected from any one or more mixture in microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, carboxymethyl starch sodium, low-substituted hydroxypropyl methylcellulose, starch, tween, the sodium lauryl sulphate according to claim 1-4;
Described filler is selected from any one or more mixture in microcrystalline Cellulose, microcrystalline Cellulose-mannitol, microcrystalline Cellulose-micropowder silica gel, lactose, starch, modified starch-1500, mannitol, sorbitol, xylitol, erythrose, pregelatinized Starch, Icing Sugar, glucose, dextrin, the calcium sulfate;
Described antacid is selected from citric acid, ascorbic acid, lactic acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, glycolic acid, aminoacid, and derivant;
Described correctives is selected from any one or more mixture of stevioside, Icing Sugar, Liquoride sugar element, Aspartane, sucralose, cyclamate, Talin, glucide;
Described binding agent is selected from any one or more mixture in purified water, ethanol, starch slurry, hydroxypropyl first methylcellulose, polyvinylpyrrolidone, carbomer, dextrin, gelatine size, mucialga of arabic gummy, sodium alginate and the syrup;
Described lubricant is selected any one or more mixture in stearic acid, magnesium stearate, calcium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycol 6000, Macrogol 4000, sodium lauryl sulphate, the fumaric acid sodium stearate.
12. a kind of dronedarone hydrochloride pharmaceutical composition according to claim 11 it is characterized in that by the administration of sublingual administration mode.
13. the preparation method of described a kind of dronedarone hydrochloride pharmaceutical composition is characterized in that comprising the steps: according to claim 1-12
(1) binding agent and antacid are dissolved in prepare binder solution in the suitable quantity of water;
(2) principal agent dronedarone hydrochloride, filler, disintegrating agent, correctives, lubricant are carried out drying, the pretreatment of sieving;
(3) with pretreated principal agent, filler, disintegrating agent, correctives mix homogeneously;
(4) binder solution is added in the above-mentioned material of mixing, make soft material, granulate 40-60 ℃ of drying;
(5) add the lubricant mixing in the dried granule, tabletting gets finished product again.
14. preparation method according to claim 13 is characterized in that: sieve in the described step (2) as passing through 60 mesh sieves; Baking temperature is 50 ℃ in the step (4).
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104721178A (en) * | 2015-03-25 | 2015-06-24 | 河北仁合益康药业有限公司 | Composition for dronedarone hydrochloride tablet and preparation method thereof |
| CN108042501A (en) * | 2017-12-28 | 2018-05-18 | 广东伊茗药业有限公司 | A kind of Dronedarone hydrochloride tablet without surfactant |
| CN108042500A (en) * | 2017-12-19 | 2018-05-18 | 佛山市弘泰药物研发有限公司 | A kind of dronedarone hydrochloride oral disintegrating tablet and preparation method thereof |
| CN114377148A (en) * | 2020-10-20 | 2022-04-22 | 上海博志研新药物技术有限公司 | Dronedarone hydrochloride pharmaceutical composition, preparation method and application thereof |
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| CN1267217A (en) * | 1997-06-23 | 2000-09-20 | 萨诺菲-合成实验室公司 | Solid pharmaceutical composition contg. benzofurane derivs. |
| CN101039657A (en) * | 2004-09-17 | 2007-09-19 | 赛诺菲-安万特 | Pharmaceutical composition comprising a solid dispersion with a polymer matrix containing a continuous polydextrose phase and a continuous phase of a polymer other than polydextrose |
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| CN102078307A (en) * | 2009-12-01 | 2011-06-01 | 严洁 | Medicine composition of dronedarone hydrochloride solid dispersion and preparation method thereof |
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| CN102342907A (en) * | 2010-07-30 | 2012-02-08 | 江苏恒瑞医药股份有限公司 | Dronedarone solid dispersoid and preparation method thereof |
| CN102349889A (en) * | 2011-11-01 | 2012-02-15 | 江苏先声药物研究有限公司 | Composition containing dronedarone |
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| CN104721178A (en) * | 2015-03-25 | 2015-06-24 | 河北仁合益康药业有限公司 | Composition for dronedarone hydrochloride tablet and preparation method thereof |
| CN108042500A (en) * | 2017-12-19 | 2018-05-18 | 佛山市弘泰药物研发有限公司 | A kind of dronedarone hydrochloride oral disintegrating tablet and preparation method thereof |
| CN108042501A (en) * | 2017-12-28 | 2018-05-18 | 广东伊茗药业有限公司 | A kind of Dronedarone hydrochloride tablet without surfactant |
| CN114377148A (en) * | 2020-10-20 | 2022-04-22 | 上海博志研新药物技术有限公司 | Dronedarone hydrochloride pharmaceutical composition, preparation method and application thereof |
| WO2022083636A1 (en) * | 2020-10-20 | 2022-04-28 | 上海博志研新药物技术有限公司 | Dronedarone hydrochloride pharmaceutical composition, and preparation method therefor and use thereof |
| CN114377148B (en) * | 2020-10-20 | 2023-09-29 | 上海博志研新药物研究有限公司 | Dronedarone hydrochloride pharmaceutical composition, preparation method and application thereof |
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