CN102885795A - Trimetazidine dihydrochloride sustained-release tablet and preparation method thereof - Google Patents
Trimetazidine dihydrochloride sustained-release tablet and preparation method thereof Download PDFInfo
- Publication number
- CN102885795A CN102885795A CN2012104286422A CN201210428642A CN102885795A CN 102885795 A CN102885795 A CN 102885795A CN 2012104286422 A CN2012104286422 A CN 2012104286422A CN 201210428642 A CN201210428642 A CN 201210428642A CN 102885795 A CN102885795 A CN 102885795A
- Authority
- CN
- China
- Prior art keywords
- trimetazidine hydrochloride
- sustained
- release tablets
- release
- hydrochloride sustained
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Abstract
The invention discloses a trimetazidine dihydrochloride sustained-release tablet and a preparation method thereof. The trimetazidine dihydrochloride sustained-release tablet comprises the following constituents in percentage by mass: 5-60% of trimetazidine dihydrochloride, 10-25% of sustained-release framework material, 1-8% of adhesive, 20-80% of filler, 0.1-5% of glidant and 0.2-3% of lubricant. According to the trimetazidine dihydrochloride sustained-release tablet, medicine can be slowly and uniformly released by adding the sustained-release framework material, so as to achieve regulation and control for a release speed, reduce the peak-valley ratio of the medicine, improve the efficacy, reduce the toxic and side effects of the medicine, reduce daily medicine-taking times and enhance the compliance of the patient on the medicine. The preparation method of the trimetazidine dihydrochloride sustained-release tablet disclosed by the invention is simple in process, does not need specially process production equipment, and is low in cost and good for batch amplification and industrialized production for products.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, particularly relate to slow releasing tablet of new class anti-anginal drug Trimetazidine Hydrochloride and preparation method thereof.
Background technology
Trimetazidine Hydrochloride is 1-(2,3,4-trimethylphenyl) piperazine dihydrochloride, molecular formula C
14H
22N
2O
32HCl, its molecular weight is 339.3, and is soluble in water.
Trimetazidine Hydrochloride is different from the traditional treatment medicine as mainly containing nitrate esters, beta-blocker and calcium ion antagonist etc. in chemical constitution and pharmacological action, it does not rely on speed or the blood pressure drops of heart, it has the effect to antiadrenergic drug, norepinephrine and vassopressin, can reduce vascular resistance, increase coronary flow and reach blood flow on every side, promote the generation of myocardial metabolism and cardiac energy.Can reduce simultaneously the heart working load, reduce the consumption of myocardial oxygen consumption and cardiac energy, thereby improve the equilibrium of supply and demand of myocardium oxygen.Still can strengthen the toleration to cardiac glycoside.
Trimetazidine Hydrochloride (Trimetazidine Diridrohlorid, TMZ) as the representative of the new class metabolic medicine of angina pectoris prevention and treatment, in Europe and a plurality of range of countries extensive uses, and be proved to be treatment angina pectoris aspect good efficacy is arranged, enter China in 2000, now listed National essential drugs list in.
The Trimetazidine Hydrochloride conventional tablet, tablet specification 20mg/ sheet.For guaranteeing enough plasma concentration, require take medicine every day 2-3 time, the most often requiring the dosage scheme during treating is every day 3 times.Because busy patient or old people have the danger of forgetting, therefore, the scheme of repeatedly taking medicine is unfavorable to this class crowd.Trimetazidine Hydrochloride absorbs fast and half-life short (approximately 6h) in vivo, it can reach high peak serum concentration at short notice after taking, and the blood drug level when next medication is very low, ischemia the most serious early morning particularly, the weak curative effect of general formulation, the side reaction that brings to patient is larger.
Slow releasing preparation can provide evenly constant blood drug level, improves the safety of medication and effectiveness and patient's compliance and control drug plasma level and reduction administration frequency.Shi Weiya (Tianjin) pharmaceutical Co. Ltd began the trimetazidine hydrochloride sustained-release tablets that goes on the market in 2010, English name Trimetazidine Dihydrochloride Modified Release Tablets, the trade name vasorel, tablet specification 35mg/ sheet, main component is Trimetazidine Hydrochloride.
The patent No. provides the substrate tablet that can discharge for a long time trimetazidine behind the oral administration for CN00138060.5, it is characterized in that not containing in substrate tablet hydrophobicity composition and long-time release is to control by mixing with the hypromellose (HypromelloseCellulose, HPMC) that accounts for tablet total weight 25-50%.The trimetazidine dihydrochloride accounts for tablet total weight 15-30% in the tablet, and binding agent PVP accounts for tablet total weight 3-12%, diluent CaHPO
42H
2O accounts for tablet total weight 25-75%, and all the other are the anhydrous colloidal state SiO of magnesium stearate lubricant and flowable
2, carry out wet granulation.
The patent No. is CN201110286002.8 trimetazidine hydrochloride sustained-release tablets and preparation method thereof, disclosing Trimetazidine Hydrochloride content is 7.34-15.97%, polyoxyethylene content 21.98-49.63%, dextrin content 21.98-49.63%, 3-10% ethyl cellulose cellulose content 11.65-29.15%, magnesium stearate content 0.54-1.64% carries out wet granulation.
The patent No. is the oral trimetazidine drug regimen that delays to discharge of CN95103558.4; the control of guaranteeing trimetazidine by the depots system discharges; described system is selected from the insoluble polymer of EC and polymethacrylic acid polymer and the mixture of plasticizer citroflex A-4 forms film; this film is wrapped in tablet or pill granule, and method of granulating is wet granulation.
The patent No. is ZL200610166205.2 sustained-release micro-pellet of trimetazidine and preparation method thereof, it is 20 that the weight ratio of the film-coat layer that contains pill core control drug release is provided: 1-5: 1, the content of trimetazidine is 10-60% in the ball core, main employing is extruded spheronization and is prepared the ball core, and fluid bed carries out sustained release coating.
There are following problem in prescription or the preparation technology of above-mentioned slow releasing tablet, slow-release micro-pill and release membranes bag sheet:
1. the HPMC of higher proportion and CaHPO
42H
2The O combination causes in the wet granulation process, and the pulverizing difficulty of granule is higher after the soft material that the wet granulation acquisition is suitable and the wet granulation drying, and is also relatively high to the requirement of equipment;
2. the skeleton that adopts polyethylene glycol oxide (Poly Ethylene Oxide, PEO) to discharge for label control, not high but PEO forms gel strength, larger to the drug release stability influence; Simultaneously, 65 ℃-67 ℃ of PEO vitrification points, heat stability is bad, baking temperature can not be too high, causes in the tablet manufacture and may have problems, in the deposit process, because Oxidation, PEO also can produce free radical, can cause the degraded of adjuvant and reactive compound, is unfavorable for the long preservation of product.
3. the production technology of slow-release micro-pill or release membranes coated tablet is comparatively complicated, needs production equipment expensive, invests greatlyr, and cost is higher.
Summary of the invention
Based on this, the invention provides a kind of quality stability is good, preparation technology is simple, production cost is low trimetazidine hydrochloride sustained-release tablets and preparation method.
A kind of trimetazidine hydrochloride sustained-release tablets is calculated in mass percent, and comprises following component:
Among some embodiment, be calculated in mass percent therein, comprise following component:
Among some embodiment, be calculated in mass percent therein, comprise following component:
The sustained-release matrix material is to regulate drug release time to reach the purpose of slow release; Binding agent is to make the less or noncohesive materials from bonding of viscosity become pressed powder or the thick liquid of the tool viscosity of granule or compression forming; Filler is weight and the volume that increases tablet, is beneficial to the adjuvant of divided dose and molding; Fluidizer can stick to granule or powder surface the recess of rough surface will be filled up, and granule is separated, and reduce the frictional force between the granule, thereby improve the flowability of granule; In order feeding in raw material smoothly and slice, to reduce the friction between friction, tablet and the punch die between the granule when lubricant refers to tabletting, to reduce a kind of material that sticking adds with increasing unilateral smooth and beautiful appearance.
Therein among some embodiment, described sustained-release matrix material is selected from ethyl cellulose, hydroxyethyl-cellulose, hydroxyethylmethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose (3000mPas-120000mPas), hydroxy methocel, Carboxymethyl cellulose sodium, pectin, agar, Glyceryl Behenate, vinylacetate, glyceryl monostearate, polyvidone, in the carbomer one or more, described filler is selected from microcrystalline Cellulose, calcium hydrogen phosphate, calcium carbonate, amylum pregelatinisatum, lactose, dextrin, mannitol, especially strange, in the pregelatinized Starch one or more, described binding agent is selected from polyvidone, hydroxypropyl methylcellulose (3mPas-6mPas), refined gram is suitable, methylcellulose, sodium carboxymethyl cellulose, polyvinyl alcohol, gelatin, in the arabic gum one or more, described fluidizer is selected from one or both in micropowder silica gel or the Pulvis Talci, and described lubricant is selected from magnesium stearate, stearic acid, in the calcium stearate one or more.
Therein among some embodiment, described sustained-release matrix material is selected from hydroxypropyl methylcellulose (3000mPas-120000mPas), hydroxypropyl cellulose, polyvidone, carbomer, Glyceryl Behenate, in the vinylacetate one or more, described filler is selected from calcium hydrogen phosphate, microcrystalline Cellulose, mannitol, in the pregelatinized Starch one or more, described binding agent is selected from polyvidone, in the hydroxypropyl methylcellulose (3mPas-6mPas) one or both, described fluidizer is micropowder silica gel, and described lubricant is selected from magnesium stearate, in the stearic acid one or both.Wherein, the hydrophilic gel such as hydroxypropyl methylcellulose, hydroxypropyl cellulose skeleton has good water-retaining property, caking property, pH value stability, salt discharge, thickening capabilities, anti-enzyme and dispersibility, after slow releasing tablet is ingested, sustained-release matrix tablets is in aqueous solution or gastro-intestinal Fluid, it is wet that the surface of tablet becomes, and polymer hydration around skeleton forms gel layer, and polymer transforms from the glassy state to the gel state, in this stage, label keeps dry substantially.When more water was penetrated into matrix core, gel layer thickened along with passage of time, for drug release provides barrier.
Among some embodiment, the dosage form of described trimetazidine hydrochloride sustained-release tablets is tablet therein, and the amount that contains described Trimetazidine Hydrochloride in every described trimetazidine hydrochloride sustained-release tablets is 20mg or 35mg.
Therein among some embodiment, the amount that contains described Trimetazidine Hydrochloride in every described trimetazidine hydrochloride sustained-release tablets is 35mg.
A kind of method for preparing above-mentioned trimetazidine hydrochloride sustained-release tablets may further comprise the steps:
(1), mix: with load weighted Trimetazidine Hydrochloride, sustained-release matrix material, filler, binding agent mix homogeneously, the part mix lubricant in the prescription then;
(2), granulate: with the medicine of mix homogeneously and the mixture of adjuvant, be compressed into sheet or plate object, crushing and pelletizing then sieves;
(3), total mixed: as to mix with described fluidizer, again with remaining mix lubricant;
(4), tabletting: tabletting, and get final product.
Wherein, Trimetazidine Hydrochloride and other adjuvants being sieved, is for each component is better disperseed, and mixes more evenly, improves tablet medicine content uniformity.Trimetazidine Hydrochloride, sustained-release matrix material, filler, binding agent being mixed, and granulate, is in order to improve the flowability of mixtures of materials, also to have the advantages such as good looking appearance, wearability are strong, compressibility is good.Granulate is in order to smash the bulk granule, the function such as have the particle size distribution of optimization, tablet weight is even, tablet content is even.Granule behind the granulate and fluidizer are mixed to evenly, are for fluidizer is distributed in the Trimetazidine Hydrochloride medicine-containing particle fully, thereby improve the flowability of Trimetazidine Hydrochloride medicine-containing particle.Adding at last lubricant, is in order to help the attractive in appearance of tabletting and tablet, behind the tabletting, to make trimetazidine hydrochloride sustained-release tablets provided by the invention again.
Among embodiment, described step (1) adopts dry granulation therein.
Among some embodiment, described step (2) is crossed 20-40 mesh sieve crushing and pelletizing therein.
Among some embodiment, also have the step of coating after the described step (4) therein, the required film-coat material of described coating steps is selected from one or more in the cellulose derivative.Tablet is carried out coating, is in order to improve outward appearance, be convenient to store, conveniently take, cover abnormal smells from the patient, to improve the purposes such as drug quality and stability.
The inventor gropes by a large amount of tests, has found a kind of pharmaceutical composition of new Trimetazidine Hydrochloride, can be used for the Controlled release of Trimetazidine Hydrochloride, and prescription and preparation technology have following characteristics:
1, the consumption that is used for the HPMC of control active component release significantly reduces, and has reduced cost;
2, pass through to regulate the ratio of filler and skeleton releasable material, effectively the rate of release of control and regulating drug;
3, the sustained-release matrix material of proportioning of the present invention and other adjuvants adopt dry granulation, can more effectively solve adjuvant adhesion equipment, the problem that is difficult to clean adopts the preparation technology of dry granulation to simplify preparation process, has reduced cost, saved the energy, reduced labour expenditure, energy-conserving and environment-protective.
Trimetazidine hydrochloride sustained-release tablets of the present invention utilizes the sustained-release matrix material can slowly discharge uniformly the property of medicine, reach the reduction rate of release, postpone peak time, reduce medicining times every day, improve patient to the compliance of medicine, and described hydrochloric acid Sibutramine Hydrochloride sustained-release tablet recipe is simple, has good quality stability.In addition, the preparation method of described trimetazidine hydrochloride sustained-release tablets have technological operation simple, need not special handling production equipment, production cost low, be fit to technology production, be conducive to the suitability for industrialized production of batch amplification of product.Described preparation method yield is high simultaneously, and operation is simple for granulation and pulverizing process, and intermediate material good stability, flowability and compressibility are good, the content good uniformity, satisfy the requirement of tabletting fully, and the tablet surface that makes simultaneously is smooth attractive in appearance.
Description of drawings
Fig. 1 is the release in vitro curve chart of trimetazidine hydrochloride sustained-release tablets in medium 0.1molHCl of embodiment 1;
Fig. 2 is the release in vitro curve chart of trimetazidine hydrochloride sustained-release tablets in medium pH4.5 of embodiment 1;
Fig. 3 is the release in vitro curve chart of trimetazidine hydrochloride sustained-release tablets in medium pH6.8 of embodiment 1;
Fig. 4 is the release in vitro curve chart of trimetazidine hydrochloride sustained-release tablets in WATER AS FLOW MEDIUM of embodiment 1;
Fig. 5 is the release in vitro curve chart of trimetazidine hydrochloride sustained-release tablets in WATER AS FLOW MEDIUM of embodiment 3;
Fig. 6 is the release in vitro curve chart of trimetazidine hydrochloride sustained-release tablets in WATER AS FLOW MEDIUM of embodiment 6;
Fig. 7 is the release in vitro curve chart of trimetazidine hydrochloride sustained-release tablets in WATER AS FLOW MEDIUM of embodiment 9;
Fig. 8 is the trimetazidine hydrochloride sustained-release tablets of embodiment 1 and the commercially available hydrochloric acid Sibutramine Hydrochloride slow releasing tablet concentration comparison diagram of Trimetazidine Hydrochloride in the different time blood plasma after administration.
The specific embodiment
The present invention is further elaborated below in conjunction with specific embodiment.
Employed Trimetazidine Hydrochloride is available from Wuhan Wuyao Pharmaceutical Co., Ltd in following examples; Wet granulator is available from Yingge Granulating Covering Technology Co., Ltd., Chongqing, and model is EMG2-6; Three-dimensional stereo mixing machines is available from Taizhou pharmaceutical machine at dawn company limited, and model is HD-5; Fluid bed is available from Yingge Granulating Covering Technology Co., Ltd., Chongqing, and model is WBF-2G; Tablet machine is available from upper island space plant equipment company limited, and model is ZP-5; Chufa-type coating pan is available from the safe pharmaceutical machine company limited of Jiangsu Province's Taizhou City gold, and model is: BY-400.
A kind of trimetazidine hydrochloride sustained-release tablets comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, get Trimetazidine Hydrochloride fine powder, hydroxypropyl methylcellulose (12000mPas-21000mPas), polyvidone, calcium hydrogen phosphate and cross 40 mesh sieves, get micropowder silica gel and stearic acid and cross 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, hydroxypropyl methylcellulose (12000mPas-21000mPas) 48.00g, polyvidone 12.00g, calcium hydrogen phosphate 103.60g, micropowder silica gel 0.40g, stearic acid 2.00g, 10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), mix: load weighted Trimetazidine Hydrochloride, hydroxypropyl methylcellulose (12000mPas-21000mPas), polyvidone, calcium hydrogen phosphate, micropowder silica gel are mixed 30min in three-dimensional stereo mixing machines, add again stearic acid 1.00g and mixed two minutes;
(4), dry granulation: the material that mixes is carried out dry granulation, and the material that dry granulation makes is crossed 20 mesh sieve crushing and pelletizings;
(5), always mix: the granule behind the granulate is added in the three-dimensional stereo mixing machines with stearic acid 1.00g mixed two minutes.
(6), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 8kg, and the heavy 201mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(7), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 98.80%.
A kind of trimetazidine hydrochloride sustained-release tablets comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, get Trimetazidine Hydrochloride fine powder, hydroxypropyl methylcellulose (80000mPas-120000mPas), polyvidone, microcrystalline Cellulose and cross 40 mesh sieves, get micropowder silica gel and magnesium stearate and cross 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, hydroxypropyl methylcellulose (80000mPas-120000mPas) 40.00g, polyvidone 16.00g, microcrystalline Cellulose 107.60g, micropowder silica gel 0.40g, magnesium stearate 2.00g, 10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), mix: load weighted Trimetazidine Hydrochloride, hydroxypropyl methylcellulose (80000mPas-120000mPas), polyvidone, microcrystalline Cellulose, micropowder silica gel are mixed 30min in three-dimensional stereo mixing machines, add again magnesium stearate 1.00g and mixed two minutes;
(4), dry granulation: the material that mixes is carried out dry granulation, and the material that dry granulation makes is crossed 20 mesh sieve crushing and pelletizings;
(5), always mix: the granule behind the granulate is added in the three-dimensional stereo mixing machines with magnesium stearate 1.00g mixed two minutes.
(6), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 8kg, and the heavy 201mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(7), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 98.15%.
A kind of trimetazidine hydrochloride sustained-release tablets comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, get Trimetazidine Hydrochloride fine powder, Glyceryl Behenate, hydroxypropyl methylcellulose, polyvidone, pregelatinized Starch and cross 40 mesh sieves, get micropowder silica gel and magnesium stearate and cross 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, Glyceryl Behenate 30.00g, hydroxypropyl methylcellulose (3000mPas-5600mPas) 16.00g, polyvidone 10.00g, pregelatinized Starch 117.60g, micropowder silica gel 0.40g, magnesium stearate 2.00g.10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), mix: load weighted Trimetazidine Hydrochloride, hydroxypropyl methylcellulose (3000mPas-5600mPas), Glyceryl Behenate, polyvidone, pregelatinized Starch, micropowder silica gel are mixed 30min in three-dimensional stereo mixing machines, then add magnesium stearate 1.00g and mixed 2 minutes;
(4), dry granulation: the material that mixes is carried out dry granulation, and the material that dry granulation makes is crossed 20 mesh sieve crushing and pelletizings;
(5), always mix: the granule behind the granulate is added in the three-dimensional stereo mixing machines with the 1.00g magnesium stearate mixed two minutes.
(6), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 9kg, and the heavy 211mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(7), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 97.79%.
A kind of trimetazidine hydrochloride sustained-release tablets comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, get Trimetazidine Hydrochloride fine powder, hydroxypropyl methylcellulose (80000mPas-120000mPas), polyvidone, microcrystalline Cellulose and cross 40 mesh sieves, ethyl cellulose is crossed 20 mesh sieves, and differential silica gel and stearic acid are crossed 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, hydroxypropyl methylcellulose (80000mPas-120000mPas) 36.00g, ethyl cellulose 20.00g, microcrystalline Cellulose 134.80g, polyvidone 12.00g, micropowder silica gel 0.60g, magnesium stearate 2.60g; 10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), mix: Trimetazidine Hydrochloride, hydroxypropyl methylcellulose (80000mPas-120000mPas), ethyl cellulose, microcrystalline Cellulose, polyvidone and micropowder silica gel are added in the three-dimensional stereo mixing machines, mixed 30 minutes, and in mixture, added the 1g magnesium stearate and mixed 2 minutes.
(4), dry granulation: the material that mixes is carried out dry granulation, and the material that dry granulation makes is crossed 20 mesh sieve crushing and pelletizings;
(5), total mixed: that the granule behind the granulate was mixed 2 minutes with the 1.6g magnesium stearate;
(6), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 8kg, and the heavy 241mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(7), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 96.80%.
A kind of trimetazidine hydrochloride sustained-release tablets comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, get Trimetazidine Hydrochloride fine powder, hydroxypropyl methylcellulose (12000mPas-21000mPas), carbomer, microcrystalline Cellulose, mannitol and cross 40 mesh sieves, micropowder silica gel and stearic acid are crossed 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, hydroxypropyl methylcellulose (12000mPas-21000mPas) 32.00g, carbomer 10.00g, microcrystalline Cellulose 75.00g, mannitol 60.00g, micropowder silica gel 0.5g, stearic acid 2.50g.10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), Trimetazidine Hydrochloride, hydroxypropyl methylcellulose (12000mPas-21000mPas), carbomer, microcrystalline Cellulose, mannitol and differential silica gel were mixed in three-dimensional stereo mixing machines 30 minutes, then the gained mixture mixed 2 minutes with stearic acid 1.00g;
(4), dry granulation: the material that mixes is carried out dry granulation, and the material that dry granulation makes is crossed 20 mesh sieve crushing and pelletizings;
(4), total mixed: that the granule behind the granulate was mixed 2 minutes with the 1.5g stearic acid;
(5), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 7kg, and the heavy 226mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(6), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 98.12%.
A kind of trimetazidine hydrochloride sustained-release tablets comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, (the vinylacetate mass fraction is 76% to get the mixture of Trimetazidine Hydrochloride fine powder, hydroxypropyl methylcellulose (80000mPas-120000mPas), vinylacetate and polyvidone, the mass fraction of polyvidone is 24%), microcrystalline Cellulose crosses 40 mesh sieves, Pulvis Talci and magnesium stearate are crossed 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, hydroxypropyl methylcellulose (80000mPas-120000mPas) 26.00g, vinylacetate 27.00g, polyvidone 8.50g, microcrystalline Cellulose 127.00g, Pulvis Talci 5.00g, stearic acid 2.50g; 10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), Trimetazidine Hydrochloride, hydroxypropyl methylcellulose (80000mPas-120000mPas), vinylacetate, polyvidone, microcrystalline Cellulose and Pulvis Talci were mixed in three-dimensional stereo mixing machines 30 minutes, then the gained mixture was mixed 2 minutes with stearic acid 1.00g;
(4), dry granulation: the material that mixes is carried out dry granulation, and the material that dry granulation makes is crossed 20 mesh sieve crushing and pelletizings;
(4), total mixed: that the granule behind the granulate was mixed 2 minutes with the 1.50g stearic acid;
(5), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 8kg, and the heavy 231mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(6), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 97.10%.
Embodiment 7
A kind of trimetazidine hydrochloride sustained-release tablets comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, get Trimetazidine Hydrochloride fine powder, hydroxypropyl methylcellulose (80000mPas-120000mPas), hydroxypropyl methylcellulose (3mPas-6mPas), calcium hydrogen phosphate and cross 40 mesh sieves, get micropowder silica gel and stearic acid and cross 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, hydroxypropyl methylcellulose (80000mPas-120000mPas) 25.00g, hydroxypropyl methylcellulose (3mPas-6mPas) 10.00g, calcium hydrogen phosphate 121.60g, micropowder silica gel 0.40g, stearic acid 2.00g, 10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), mix: load weighted Trimetazidine Hydrochloride, hydroxypropyl methylcellulose (80000mPas-120000mPas), hydroxypropyl methylcellulose (3mPas-6mPas), calcium hydrogen phosphate, micropowder silica gel are mixed 30min in three-dimensional stereo mixing machines, add again stearic acid 1.00g and mixed two minutes;
(4), dry granulation: the material that mixes is carried out dry granulation, and the material that dry granulation makes is crossed 20 mesh sieve crushing and pelletizings;
(5), always mix: the granule behind the granulate is added in the three-dimensional stereo mixing machines with stearic acid 1.00g mixed two minutes.
(6), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 8kg, and the heavy 194mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(7), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 98.26%.
Embodiment 8
A kind of trimetazidine hydrochloride sustained-release tablets comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, get Trimetazidine Hydrochloride fine powder, hydroxypropyl methylcellulose (12000mPas-21000mPas), carbomer, microcrystalline Cellulose, mannitol and cross 40 mesh sieves, micropowder silica gel and stearic acid are crossed 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, hydroxypropyl methylcellulose (12000mPas-21000mPas) 30.00g, carbomer 11.00g, hydroxypropyl methylcellulose (3mPas-6mPas) 7.40g, microcrystalline Cellulose 139.50g,, micropowder silica gel 0.60g, magnesium stearate 2.50g.10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), mix: described Trimetazidine Hydrochloride, hydroxypropyl methylcellulose, carbomer, microcrystalline Cellulose, micropowder silica gel are mixed 30min in three-dimensional stereo mixing machines, add again stearic acid and mixed two minutes;
(4), dry granulation: the material that mixes is carried out dry granulation, and the material that dry granulation makes is crossed 20 mesh sieve crushing and pelletizings;
(5), always mix: the granule behind the granulate is added in the three-dimensional stereo mixing machines with stearic acid 1.00g mixed two minutes.
(6), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 8kg, and the heavy 226mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(7), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 97.06%.
Embodiment 9
A kind of trimetazidine hydrochloride sustained-release tablets comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, get excessively 40 mesh sieves of Trimetazidine Hydrochloride fine powder, hydroxypropyl methylcellulose (12000mPas-21000mPas), hydroxypropyl methylcellulose (3mPas-6mPas), calcium hydrogen phosphate, microcrystalline Cellulose 102, get micropowder silica gel and stearic acid and cross 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, hydroxypropyl methylcellulose (12000mPas-21000mPas) 44.00g, hydroxypropyl methylcellulose (3mPas-6mPas) 10.00g, calcium hydrogen phosphate 48.00g, microcrystalline Cellulose 10260.6g, micropowder silica gel 0.40g, stearic acid 2.00g, 10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), mix: load weighted Trimetazidine Hydrochloride, hydroxypropyl methylcellulose (12000mPas-21000mPas), hydroxypropyl methylcellulose (3mPas-6mPas), calcium hydrogen phosphate, microcrystalline Cellulose 102, micropowder silica gel are mixed 30min in three-dimensional stereo mixing machines, add again stearic acid and mixed two minutes;
(4), dry granulation: the material that mixes is carried out dry granulation, and the material that dry granulation makes is crossed 20 mesh sieve crushing and pelletizings;
(5), always mix: the granule behind the granulate is added in the three-dimensional stereo mixing machines with stearic acid mixed two minutes.
(6), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 8kg, and the heavy 200mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(7), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 98.57%.
The trimetazidine hydrochloride sustained-release tablets of matched group comprises a high proportion of sustained-release matrix material, adopts common wet granulation technology to make, and specifically comprises following component (by 1000):
Prepare the method for above-mentioned trimetazidine hydrochloride sustained-release tablets, may further comprise the steps:
(1), grinds and sieve: Trimetazidine Hydrochloride is ground to form fine powder, get Trimetazidine Hydrochloride fine powder, hydroxypropyl methylcellulose (3000mPas-5600mPas), polyvidone, calcium hydrogen phosphate, cross 40 mesh sieves, get micropowder silica gel and stearic acid and cross 80 mesh sieves;
(2), weighing: accurately take by weighing Trimetazidine Hydrochloride 35.00g, hydroxypropyl methylcellulose (3000mPas-5600mPas) 74.00g, polyvidone 8.70g, calcium hydrogen phosphate 80.90g, micropowder silica gel 0.40g, stearic acid 1.00g, 10.00g is for subsequent use for Opadry (the thin film dress material is hydroxypropyl methylcellulose);
(3), wet granulation: load weighted Trimetazidine Hydrochloride, polyvidone, calcium hydrogen phosphate are mixed, then use the pure water of capacity with moistening mixture, utilize wet granulator, carry out wet granulation, the adjusting mixing velocity is 400rpm, shear rate is that 600rpm granulates, and drying gets medicine-containing particle, and medicine-containing particle is carried out granulate;
(4), mix: the granule that wet granulation is made mixes with hydroxypropyl methylcellulose, and incorporation time 20 minutes is mixed rotating speed 25rpm.
(5), always mix: step is added in the three-dimensional stereo mixing machines with stearic acid mixed two minutes.
(6), tabletting: regulating tabletting speed is 15rpm, and tablet hardness is 8kg, and the heavy 200mg of sheet carries out tabletting with always mixed material; In its process, heavy to sheet, hardness, friability etc. carry out tracking measurement with the corresponding index that guarantees the tablet requirement in controlled range;
(7), coating: the trimetazidine hydrochloride sustained-release tablets that makes is carried out the Opadry coating, with the trimetazidine hydrochloride sustained-release tablets that makes behind the Opadry coating, the content of trimetazidine hydrochloride sustained-release tablets is the 35mg/ sheet in every trimetazidine hydrochloride sustained-release tablets, and yield is 95%.
Matched group product prescription cost (1000) sees Table 1, and energy consumption and cost of labor (1000) see Table 2.
Table 1 matched group product prescription cost (1000)
| Component | Price (unit/kg) | Prescription content (g) | Prescription cost (unit) |
| Trimetazidine Hydrochloride | 1600 | 35.00 | 56 |
| Hydroxypropyl methylcellulose | 450 | 74.00 | 33.3 |
| Polyvidone | 160 | 8.70 | 1.392 |
| Calcium hydrogen phosphate | 72 | 80.90 | 5.825 |
| Micropowder silica gel | 130 | 0.40 | 0.052 |
| |
15 | 1.00 | 0.015 |
| Add up to | 200 | 96.584 |
Table 2 matched group energy consumption and cost of labor (1000)
| Prescription cost (unit) | Energy consumption cost (unit) | Cost of labor (unit) | Three add up to cost (unit) |
| 96.584 | 9 | 15 | 120.584 |
The product prescription cost (1000) of the trimetazidine hydrochloride sustained-release tablets that the embodiment of the invention 1 makes sees Table 3, and the energy and cost of labor (1000) see Table 4.
The product prescription cost (1000) of table 3 embodiment of the invention 1 trimetazidine hydrochloride sustained-release tablets
| Component | Price (unit/kg) | Prescription content (g) | Prescription cost (unit) |
| Trimetazidine Hydrochloride | 1600 | 35.00 | 56 |
[0172]
| Hydroxypropyl methylcellulose | 450 | 48.00 | 21.6 |
| Polyvidone | 160 | 12.00 | 1.92 |
| Calcium hydrogen phosphate | 72 | 103.60 | 7.459 |
| Micropowder silica gel | 130 | 0.40 | 0.052 |
| |
15 | 2.00 | 0.03 |
| Add up to | 201 | 87.061 |
The energy consumption of table 4 embodiment of the invention 1 trimetazidine hydrochloride sustained-release tablets and cost of labor (1000)
| Prescription cost (unit) | Energy consumption cost (unit) | Cost of labor (unit) | Three add up to cost (unit) |
| 87.061 | 4 | 6 | 97.061 |
Compare with matched group, the production cost of the embodiment of the invention 1 trimetazidine hydrochloride sustained-release tablets has descended 19.5%.
The product prescription cost (1000) of the trimetazidine hydrochloride sustained-release tablets that the embodiment of the invention 8 makes sees Table 5, and energy consumption and cost of labor (1000) see Table 6.
The trimetazidine hydrochloride sustained-release tablets product prescription cost (1000) of table 5 embodiment of the invention 8
| Component | Price (unit/kg) | Prescription content (g) | Prescription cost (unit) |
| Trimetazidine Hydrochloride | 1600 | 35.00 | 56 |
| Hydroxypropyl methylcellulose | 450 | 37.40 | 16.832 |
| Carbomer | 150 | 11.00 | 1.65 |
| Microcrystalline Cellulose | 58 | 139.50 | 8.091 |
| Micropowder silica gel | 130 | 0.60 | 0.078 |
| |
15 | 2.50 | 0.0375 |
| Add up to | 226 | 82.687 |
The trimetazidine hydrochloride sustained-release tablets energy consumption of table 6 embodiment of the invention 8 and cost of labor (1000)
| Prescription cost (unit) | Energy consumption cost (unit) | Cost of labor (unit) | Three add up to cost (unit) |
[0181]
| 82.687 | 4 | 6 | 92.687 |
Compare with matched group, the production cost of the trimetazidine hydrochloride sustained-release tablets of the embodiment of the invention 8 has descended 23.1%.
The trimetazidine hydrochloride sustained-release tablets that other embodiments of the invention provide, compare with the trimetazidine hydrochloride sustained-release tablets that matched group makes, the production cost 19.5%-23.1% that descended, comprehensive the above results, trimetazidine hydrochloride sustained-release tablets provided by the invention is compared with matched group, the production cost 19.5%-23.1% that descended.
Reach external related experiment in the body of trimetazidine hydrochloride sustained-release tablets of the present invention as follows:
1, measure the method for trimetazidine hydrochloride sustained-release tablets vitro release: the device of employing vitro release algoscopy (2010 editions two appendix XD first methods of Chinese Pharmacopoeia) and employing stripping algoscopy (2010 editions two appendix XC first methods of Chinese Pharmacopoeia) is measured the drug release characteristics of the trimetazidine hydrochloride sustained-release tablets of the embodiment of the invention 1.
The present invention has selected 0.1molHCl, pH4.5, pH6.8 and water as the gastroenteric environment in the dissolution medium analogue body, is subjected to the intestines and stomach pH value to affect situation to estimate this preparation medicine release characteristic, and the result who obtains is as follows:
Experimental result such as Fig. 1-shown in Figure 7, trimetazidine hydrochloride sustained-release tablets release in vitro result of the present invention shows that trimetazidine hydrochloride sustained-release tablets of the present invention can discharge medicine slowly in four kinds of media, and release characteristic is subjected to the impact of medium less, in clinical use procedure near the release medicine of constant speed, for the patient provides more steady and lasting curative effect.
2, the pharmacokinetics of trimetazidine hydrochloride sustained-release tablets experiment
Sample:
Reference substance: trimetazidine hydrochloride sustained-release tablets (Wan Lishuan): specification 35mg/ sheet, commercially available is Shi Weiya (Tianjin) pharmaceutical Co. Ltd;
The trimetazidine hydrochloride sustained-release tablets of the invention process 1.
Test method:
18 of beasle dogs are divided into three groups at random, take commercially available trimetazidine hydrochloride sustained-release tablets (Wan Lishuan, 35mg) as control formulation, carry out bioavailability and pharmacokinetic.Give embodiment trimetazidine hydrochloride sustained-release tablets and each 70mg of commercially available trimetazidine hydrochloride sustained-release tablets of 1 preparation.The concentration of Trimetazidine Hydrochloride in the different time blood plasma is drawn blood drug level-time graph after the administration of employing high effective liquid chromatography for measuring.The result is as shown in Figure 8:
The result of the trimetazidine hydrochloride sustained-release tablets of the embodiment of the invention 1 and commercially available hydrochloric acid Sibutramine Hydrochloride slow releasing tablet shows that the concentration of Trimetazidine Hydrochloride in the different time blood plasma is and commercially available trimetazidine hydrochloride sustained-release tablets (Wan Lishuan, 35mg) be consistent, illustrate that the product of embodiment 1 and commercially available trimetazidine hydrochloride sustained-release tablets medicine generation in beasle dog is consistent, prove that this medicine is the same with the street drug drug effect.But preparation method of the present invention has that technological operation is simple, the optional majority of technique, need not special handling production equipment, production cost low, be fit to technology production, be conducive to the advantages such as suitability for industrialized production of batch amplification of product, satisfy real Production requirement.
The above embodiment has only expressed several embodiment of the present invention, and it describes comparatively concrete and detailed, but can not therefore be interpreted as the restriction to claim of the present invention.Should be pointed out that for the person of ordinary skill of the art, without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Claims (10)
1. a trimetazidine hydrochloride sustained-release tablets is characterized in that, in the quality percentage composition, comprises following component:
Described sustained-release matrix material is selected from one or more in ethyl cellulose, hydroxyethyl-cellulose, hydroxyethylmethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose (3000mPas-120000mPas), hydroxy methocel, Carboxymethyl cellulose sodium, pectin, agar, Glyceryl Behenate, vinylacetate, glyceryl monostearate, polyvidone, the carbomer.
2. trimetazidine hydrochloride sustained-release tablets according to claim 1 is characterized in that, is calculated in mass percent, and comprises following component:
3. trimetazidine hydrochloride sustained-release tablets according to claim 2 is characterized in that, is calculated in mass percent, and comprises following component:
4. arbitrary described trimetazidine hydrochloride sustained-release tablets according to claim 1-3, it is characterized in that, described filler is selected from microcrystalline Cellulose, calcium hydrogen phosphate, calcium carbonate, amylum pregelatinisatum, lactose, dextrin, mannitol, one or more in strange, the pregelatinized Starch especially; Described binding agent be selected from polyvidone, hydroxypropyl methylcellulose, refined gram should, in the methylcellulose, sodium carboxymethyl cellulose, polyvinyl alcohol, gelatin, arabic gum one or more; Described fluidizer is selected from one or both in micropowder silica gel or the Pulvis Talci; Described lubricant is selected from one or more in magnesium stearate, stearic acid, the calcium stearate.
5. each described trimetazidine hydrochloride sustained-release tablets is characterized in that according to claim 1-3, hydroxypropyl methylcellulose, carbomer or Glyceryl Behenate that described sustained-release matrix material is viscosity 3000mPas-120000mPas.
6. each described trimetazidine hydrochloride sustained-release tablets is characterized in that according to claim 1-3, and described filler is selected from one or both in calcium hydrogen phosphate, the microcrystalline Cellulose; Described binding agent is selected from one or both in the hydroxypropyl methylcellulose of polyvidone, viscosity 3mPas-6mPas, and described fluidizer is micropowder silica gel; Described lubricant is magnesium stearate.
7. a method for preparing the arbitrary described trimetazidine hydrochloride sustained-release tablets of claim 1-6 is characterized in that, may further comprise the steps:
(1), mixes: behind load weighted Trimetazidine Hydrochloride, sustained-release matrix material, filler, binding agent mix homogeneously, again with the part mix lubricant;
(2), granulate: with the mixture of mix homogeneously, be compressed into sheet or plate object, crushing and pelletizing sieves;
(3), total mixed: as to mix with described fluidizer, again with remaining mix lubricant;
(4), tabletting: tabletting, and get final product.
8. the preparation method of trimetazidine hydrochloride sustained-release tablets according to claim 7 is characterized in that, adopts dry granulation in the described step (2).
9. the preparation method of trimetazidine hydrochloride sustained-release tablets according to claim 7 is characterized in that, crosses 20-40 mesh sieve crushing and pelletizing in the described step (2).
10. the preparation method of trimetazidine hydrochloride sustained-release tablets according to claim 7 is characterized in that, also has the step of coating after the described step (4).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104286422A CN102885795A (en) | 2012-10-31 | 2012-10-31 | Trimetazidine dihydrochloride sustained-release tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104286422A CN102885795A (en) | 2012-10-31 | 2012-10-31 | Trimetazidine dihydrochloride sustained-release tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102885795A true CN102885795A (en) | 2013-01-23 |
Family
ID=47529616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012104286422A Pending CN102885795A (en) | 2012-10-31 | 2012-10-31 | Trimetazidine dihydrochloride sustained-release tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102885795A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103385861A (en) * | 2013-08-06 | 2013-11-13 | 山东大学 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
| CN104274419A (en) * | 2013-07-10 | 2015-01-14 | 广东省中药研究所 | Trimetazidine hydrochloride sustained release tablet taking glyceryl behenate as framework material and preparation method of trimetazidine hydrochloride sustained release tablet |
| CN104473905A (en) * | 2014-11-20 | 2015-04-01 | 美吉斯制药（厦门）有限公司 | Trimetazidine hydrochloride sustained-release capsule and preparation method thereof |
| CN105616358A (en) * | 2016-02-17 | 2016-06-01 | 南京卓泰医药科技有限公司 | Trimetazidine sustained-release mini-pill composition and method for preparing same |
| CN108721235A (en) * | 2017-04-18 | 2018-11-02 | 江苏恒瑞医药股份有限公司 | A kind of solid composite medicament and preparation method thereof containing Trimetazidine or its salt |
| CN109908096A (en) * | 2017-12-12 | 2019-06-21 | 武汉武药科技有限公司 | A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof |
| CN110623934A (en) * | 2019-09-26 | 2019-12-31 | 杭州百诚医药科技股份有限公司 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
| CN111888476A (en) * | 2020-08-17 | 2020-11-06 | 深圳市道科思医药有限公司 | Modified release pharmaceutical composition of trimetazidine dihydrochloride |
| CN112315942A (en) * | 2020-11-04 | 2021-02-05 | 南京康川济医药科技有限公司 | Trimetazidine hydrochloride sustained release preparation and preparation method thereof |
| CN113350306A (en) * | 2021-07-14 | 2021-09-07 | 浙江泰利森药业有限公司 | Nifedipine sustained release tablet and preparation process thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61212517A (en) * | 1985-03-18 | 1986-09-20 | Nippon Chemiphar Co Ltd | Long-acting tablet |
| JPH02233621A (en) * | 1989-03-07 | 1990-09-17 | Nikken Chem Co Ltd | Percutaneous absorbefacient and medicinal pharmaceutical containing the same for external use |
| CN101455668A (en) * | 2007-12-14 | 2009-06-17 | 北京琥珀光华医药科技开发有限公司 | Preparation of trimetazidine hydrochloride sustained-release tablets and use thereof |
| WO2011112160A1 (en) * | 2010-03-12 | 2011-09-15 | Ali Raif Ilac Sanayi Ve Ticaret A.S. | Extended release trimetazidine tablets |
| CN102319225A (en) * | 2011-09-23 | 2012-01-18 | 广州白云山光华制药股份有限公司 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
-
2012
- 2012-10-31 CN CN2012104286422A patent/CN102885795A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61212517A (en) * | 1985-03-18 | 1986-09-20 | Nippon Chemiphar Co Ltd | Long-acting tablet |
| JPH02233621A (en) * | 1989-03-07 | 1990-09-17 | Nikken Chem Co Ltd | Percutaneous absorbefacient and medicinal pharmaceutical containing the same for external use |
| CN101455668A (en) * | 2007-12-14 | 2009-06-17 | 北京琥珀光华医药科技开发有限公司 | Preparation of trimetazidine hydrochloride sustained-release tablets and use thereof |
| WO2011112160A1 (en) * | 2010-03-12 | 2011-09-15 | Ali Raif Ilac Sanayi Ve Ticaret A.S. | Extended release trimetazidine tablets |
| CN102319225A (en) * | 2011-09-23 | 2012-01-18 | 广州白云山光华制药股份有限公司 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 李林: "盐酸曲美他嗪缓释片的处方工艺筛选", 《制剂与技术》, vol. 9, no. 6, 29 February 2012 (2012-02-29), pages 99 - 100 * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274419A (en) * | 2013-07-10 | 2015-01-14 | 广东省中药研究所 | Trimetazidine hydrochloride sustained release tablet taking glyceryl behenate as framework material and preparation method of trimetazidine hydrochloride sustained release tablet |
| CN103385861A (en) * | 2013-08-06 | 2013-11-13 | 山东大学 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
| CN104473905A (en) * | 2014-11-20 | 2015-04-01 | 美吉斯制药（厦门）有限公司 | Trimetazidine hydrochloride sustained-release capsule and preparation method thereof |
| CN105616358A (en) * | 2016-02-17 | 2016-06-01 | 南京卓泰医药科技有限公司 | Trimetazidine sustained-release mini-pill composition and method for preparing same |
| CN105616358B (en) * | 2016-02-17 | 2018-12-07 | 南京卓康医药科技有限公司 | A kind of sustained-release micro-pellet of trimetazidine composition and preparation method thereof |
| CN108721235A (en) * | 2017-04-18 | 2018-11-02 | 江苏恒瑞医药股份有限公司 | A kind of solid composite medicament and preparation method thereof containing Trimetazidine or its salt |
| CN108721235B (en) * | 2017-04-18 | 2021-07-02 | 江苏恒瑞医药股份有限公司 | Solid pharmaceutical composition containing trimetazidine or salt thereof and preparation method thereof |
| CN109908096A (en) * | 2017-12-12 | 2019-06-21 | 武汉武药科技有限公司 | A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof |
| CN110623934A (en) * | 2019-09-26 | 2019-12-31 | 杭州百诚医药科技股份有限公司 | Trimetazidine hydrochloride sustained release tablet and preparation method thereof |
| CN111888476A (en) * | 2020-08-17 | 2020-11-06 | 深圳市道科思医药有限公司 | Modified release pharmaceutical composition of trimetazidine dihydrochloride |
| CN112315942A (en) * | 2020-11-04 | 2021-02-05 | 南京康川济医药科技有限公司 | Trimetazidine hydrochloride sustained release preparation and preparation method thereof |
| CN113350306A (en) * | 2021-07-14 | 2021-09-07 | 浙江泰利森药业有限公司 | Nifedipine sustained release tablet and preparation process thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102885795A (en) | Trimetazidine dihydrochloride sustained-release tablet and preparation method thereof | |
| CZ120698A3 (en) | Polymer mixture matrix for continuous release of medicaments and intended for pharmaceutical applications | |
| EP2100607A1 (en) | Pharmaceutical composition having improved storage stability | |
| CN103070864B (en) | Repaglinide and metformin hydrochloride medicinal composition and its preparation method | |
| CN103908456B (en) | Tenofovir, lamivudine and efavirenz three compound recipe pellet tablet and preparation method thereof | |
| WO2023078180A1 (en) | Mini-tablet, and preparation method therefor and formulation thereof | |
| CN103768063B (en) | A kind of moxifloxacin hydrochloride medicinal composition and preparation method thereof | |
| CN103239719A (en) | Metformin compound pharmaceutical composition and preparation method thereof | |
| CN101810628B (en) | Melbine glipizide tablet and preparation method thereof | |
| CN103610658A (en) | Immunomodulator slow-release preparation and preparation method thereof | |
| CN101791299A (en) | Method for preparing potassium citrate sustained-release tablets | |
| CN100522169C (en) | Ranolazine hydrochloride slow-release preparation and its preparing method | |
| JPWO2008072533A1 (en) | Method for producing solid preparation | |
| CN102727460B (en) | Slow-release tablets containing felodipine and metoprolo salt, and preparation method thereof | |
| CN105769905A (en) | Potassium chloride sustained release tablet and preparation method thereof | |
| CN102218043A (en) | LDH (Layered Double Hydroxides) supermolecular assembly type aspirin sustained release tablet and preparation method thereof | |
| CN104940152B (en) | A kind of pharmaceutical composition containing butanedioic acid Solifenacin | |
| CN102091053A (en) | Particle composite controlled-release tablets | |
| CN105434386A (en) | Sustained release tablet containing high water-soluble active ingredients and preparation method thereof | |
| CN109646417B (en) | Trimetazidine sustained release tablet and preparation method thereof | |
| CN102302466A (en) | Capecitabine medicinal composition capable of direct powder tableting, and application thereof | |
| CN104274419A (en) | Trimetazidine hydrochloride sustained release tablet taking glyceryl behenate as framework material and preparation method of trimetazidine hydrochloride sustained release tablet | |
| CN110200929A (en) | A kind of oral tablet and preparation method thereof containing terbinafine HCl | |
| CN104367562A (en) | Pramipexole dihydrochloride slow-release tablets and preparation method thereof | |
| CN109771380A (en) | Desmethylvenlafaxine hydrochloride drug composition and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20130123 |