CN102133195A - Trimetazidine dihydrochloride sustained control release pellet and preparation method thereof - Google Patents
Trimetazidine dihydrochloride sustained control release pellet and preparation method thereof Download PDFInfo
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Abstract
The invention relates to trimetazidine dihydrochloride sustained control release pellet and a preparation method thereof. The sustained control release pellet structurally comprises a blank pellet core, a trimetazidine dihydrochloride medicine layer and a sustained control release coating layer from inside to outside; the preparation method comprises the following steps: preparing the blank pellet core by a centrifugal coating pelletizer, putting the blank pellet core in the centrifugal coating pelletizer under a motion state, then spraying mixed liquor of adhesive and wetting agent by a spray gun until the blank pellet core is wetted, uniformly spreading the raw trimetazidine dihydrochloride on the wetted blank pellet core through a powder supplying device to obtain a medicine-containing pellet, and carrying out sustained control release coating on the exterior of the medicine-containing pellet, thus obtaining the trimetazidine dihydrochloride sustained control release pellet. The invention is suitable for preparing the trimetazidine dihydrochloride sustained control release pellet, the preparation process is simple, and a prepared pellet product is scientific and reasonable in structure, uniform in granularity and good in release degree.
Description
Technical field
The present invention relates to the slow controlled release micro pill preparation of medicine Trimetazidine Hydrochloride, exactly is slow controlled release micro pill of a kind of Trimetazidine Hydrochloride and preparation method thereof.
Background technology
Trimetazidine Hydrochloride stops the decline of ATP level in the cell by keeping the energy metabolism of cell under hypoxgia or the ischemia environment, thereby guarantees the normal function of ionic pump and the normal operation of permeable membrane sodium-potassium, keeps cell homeostasis.At present Trimetazidine Hydrochloride is widely used in the prophylactic treatment of angina pectoris attacks clinically, and dizzy and complementary symptomatic treatment tinnitus, have evident in efficacy, can share with other drug, advantage such as untoward reaction is few.
Commercially available Trimetazidine Hydrochloride raw material, tablet (20mg, trade name: vasorel, Trimetazidine) medicine, absorb rapidly after the oral administration, promptly reach plasma peaks less than 2h, eliminating the half-life approximately is 6h, and need take 3 every day at least, so intravital blood drug level is easy to occur " peak valley " phenomenon, the effective blood drug concentration weak point of holding time so not only, patient's compliance is poor.Especially take medicine evening, to morning interval long, blood drug level is very low during early morning, thereby drug effect can not steadily be brought into play.The trimetazidine hydrochloride sustained-release tablets listing that existing both at home and abroad at present day clothes are 2 times.
According to the slow releasing preparation requirement, its delivery time should prolong to some extent than ordinary preparation.Generally, prolonging dosing interval can solve by following two approach.The molecular structure of the first by revising medicine, the elimination speed that reduces medicine (
k El); It two is by reducing the rate of release of medicine from preparation to reduce the infiltration rate constant of medicine
KA.These two kinds of approach all can significantly reduce the fluctuation of blood drug level in the multiple dose administration.But utilize to reduce infiltration rate and postpone to discharge the restriction that will be subjected to some physiologic factor, as in the holdup time of absorption site, medicine is about 9-12h at the effective soak time of gastrointestinal.If infiltration rate is too slow, then some medicines can not be absorbed fully.If the some drugs half-life is 6h or shorter, it will be very difficult then designing the preparation that 24h is administered once.
The patent No. is the Chinese invention patent of ZL95103558.4, and a kind of oral trimetazidine pharmaceutical composition that delays to discharge is provided, and is sheet or the granule that is surrounded by release-controlled film.Said composition accumulative total discharges, and 6h has only disengaged the medicine less than 80%, inventor's purpose be every day single dose take, but trimetazidine T
1/2Only be 6h, and medicine has only 9-12h at the effective soak time of gastrointestinal, it is insignificant designing thus that medicine continues to discharge more than the 16h.And this process using is extruded or spheronization techniques, and wherein the micropill uniformity that obtains of expressing technique differs, and the proper sphere degree is not high; And spheronization techniques adopts celphere to spray the form that contains drug solns, adopts this mode to add medicine to and causes the medicine crystallize easily, is prone to burr, and drug loading is little, and roundness is bad, the bad control of release.
The patent No. is the Chinese invention patent of ZL200610166205.2, a kind of preparation of sustained-release micro-pellet of trimetazidine is disclosed, this patent utilization good sustained release coating material, and will be controlled at release time 8 hours, the trimetazidine drug level maintains certain concentration level like this, both improved the utilization rate of medicine, reduced the toxic and side effects of medicine again body.But some weak point still in processing technology: one is to use and extrudes spheronization and prepare micropill, and phenomenon not of uniform size can appear in the granule of this method preparation, and roundness is poor; The 2nd, contain two kinds of micropills of rapid release and slow release in the capsule, because they there are differences at bulk density and volume size.Cause medicament contg uniformity difference,, can not reach expected effect so take the wayward blood drug level in back; The 3rd, this technological operation time is long, program is complicated, cost is higher.
Summary of the invention
The technical problem to be solved in the present invention provides a kind of slow controlled release micro pill of Trimetazidine Hydrochloride, the micropill size of preparation evenly, proper sphere degree height, good fluidity, be easy to handle, slow controlled release degree is good; The diversity of preparation between during micropill batch is little, and the repeatability of micropill preparation and coating process is better; The defective of indivedual micropills in preparation is unlikely to the drug release behavior generation of whole preparation is had a strong impact on; Big at the gastrointestinal tract distribution area, the bioavailability height, zest is little; Substantially be not subjected to the gastric emptying factor affecting, the interior infiltration rate of the body of medicine is even and bioavailability among individuals difference is less; Micropill pastille percentage rate 5-40%; Even changing dosage form, micropill can not be affected as suppressing in flakes yet.
Another object of the present invention provides the preparation method of above-mentioned micropill, and this method operation is simple, equipment is simple, and is with low cost, easy operating, and can in a closed system, finish overall processes such as mother, medicine-feeding and last slow release layer, thereby enhance productivity.
The present invention will solve above-mentioned technical problem, is to realize by following technical scheme:
A kind of slow controlled release micro pill of Trimetazidine Hydrochloride, ball directly is 480-1700um, micropill shape structure comprises celphere, Trimetazidine Hydrochloride medicine layer, slow controlled release coat layer from the inside to the outside, and it is celphere 52-270 part, 20-40 parts of Trimetazidine Hydrochloride medicines, 5.5-120 parts on slow controlled release coat layer that their parts by weight close;
Make described celphere raw materials of effective components and comprise diluent, binding agent and wetting agent, wherein said diluent parts by weight are 50-240 parts, are selected from the mixture of a kind of in starch, sucrose, the microcrystalline Cellulose or at least two kinds;
Make described coatings raw materials of effective components and comprise blocker, plasticizer and wetting agent, wherein said blocker is a kind of in ethyl cellulose or the acrylic resin, and their parts by weight are respectively 6-60 parts, 8-90 parts; Described plasticizer is selected from a kind of in dibutyl sebacate, triglyceride or the triethyl citrate, and consumption is 10 ~ 20% of a blocker weight;
Described binding agent is a kind of in hydroxypropyl methylcellulose or the polyvidone, and parts by weight are respectively 2-15 parts, 6-30 parts;
Described wetting agent is 95% ethanol, and its parts by weight are 200-3000 parts.
More than form for the basic structure of micropill product of the present invention and prescription, diluent wherein is used for being in harmonious proportion the medicament contg of patent medicine, as the medicine adjuvant; The use of described binding agent is beneficial to diluent and becomes ball, also is used for combining between ingredient and celphere; The effect of wetting agent is to be used for dissolved adhesive, blocker, plasticizer as solvent; The effect of blocker is to stop drug release, controls its rate of release; The effect of plasticizer is to reduce the product brittleness, prevents to burst apart with being heated because of stressed.Prescription of the present invention and scientific and reasonable for structure, micropill size evenly, proper sphere degree height, good fluidity, be easy to handle, slow controlled release degree is good; Big at the gastrointestinal tract distribution area, the bioavailability height, zest is little; Substantially be not subjected to the gastric emptying factor affecting, the interior infiltration rate of the body of medicine is even and bioavailability among individuals difference is less; Micropill pastille percentage rate height.
The present invention also provides the preparation method of above-mentioned slow controlled release micro pill, and its basic step comprises:
1. the preparation of celphere: the celphere of preparation ball footpath 400-800 μ m;
2. prepare the pastille micropill: the mixed liquor of spray binding agent and wetting agent adheres to the celphere outer surface to the celphere surface wettability equably with medicine on celphere, makes the pastille micropill;
3. coating prepares the purpose product: coat slow controlled-release material outside the pastille micropill, make target micropill product.
As a kind of qualification of preparation method of the present invention, step is the preparation of celphere 1., and concrete operations are carried out according to the following steps order:
(11) preparation of one-level celphere
Pelletize: the powdery diluent of getting the above fineness of 100 orders, be put on the centrifugal coating pelletizing machine rotating disk, starting device, engine speed 150-250rpm, air blast flux 6-20L/min, jet flow 6-20L/min, jet pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, make pellet; Granulation process should rationally be grasped the pelletize time, and is excessive to prevent pill;
Sieve: the gained ball that sieves directly is the pellet of 400-800 μ m, can be directly as the one-level celphere, and standby;
(12) preparation of multistage celphere
The preparation of secondary celphere: the gained ball footpath of sieving, is put on the centrifugal coating pelletizing machine rotating disk as the female ball of one-level less than the pellet of 400 μ m, and remaining diluent is put into powder feeder unit; Start centrifugal coating pelletizing machine, engine speed 150-250rpm, air blast flux 0-5L/min, jet flow 6-8L/min, jet pressure 0.1MPa sprays into the mixed liquor of binding agent and wetting agent after the spray pattern, to the female ball surface wettability of one-level, open powder feeder unit for powder, the female ball of one-level is constantly grown up, sieve get ball directly be the pellet of 400-800 μ m as the secondary celphere, standby;
The preparation of three grades of celphere: the gained ball footpath of sieving less than the pellet of 400 μ m as the female ball of secondary, be put on the centrifugal coating pelletizing machine rotating disk, start centrifugal coating pelletizing machine, engine speed 150-250rpm, air blast flux 0-5L/min, jet flow 6-8L/min, jet pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, to the female ball surface wettability of secondary, open powder feeder unit for powder, the female ball of secondary is constantly grown up, and sieve is got the pellet of ball footpath 400-800 μ m as three grades of celphere, and is standby;
The preparation of level Four blank pill: the gained ball footpath of sieving less than the pellet of 400 μ m as three grades of female balls, on the centrifugal coating pelletizing machine rotating disk, start centrifugal coating pelletizing machine, engine speed 150-250rpm, air blast flux 0-5L/min, jet flow 6-8L/min, jet pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, to three grades of female ball surface wettabilities, open powder feeder unit for powder, three grades of female balls are constantly grown up, sieve get ball directly be the pellet of 400-800 μ m as the level Four celphere, standby;
……
Repeat aforesaid operations, all be prepared as the celphere of ball footpath 400-800 μ m until all diluent.
Another kind as preparation method of the present invention limits, and 2. described step prepares the pastille micropill, and concrete operations are carried out according to the following steps order:
(21) spray binding agent
Celphere is placed centrifugal coating pelletizing machine, Trimetazidine Hydrochloride is put into powder feeder unit, start centrifugal coating pelletizing machine, engine speed 200-280rpm, air blast flux 0-5L/min, jet flow 6-8L/min, whiff pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, to the celphere surface wettability; Then,
(22) medicine-feeding
Open powder feeder unit and supply powder, wait for powder to finish, be dried to water content 2-3%, take out, sieve micropill after the medicine-feeding of getting 450-1000 μ m, be the pastille micropill.
Preparation method of the present invention also has a kind of qualification, and described step 3. coating prepares target product, and concrete operations are carried out according to the following steps order:
(31) preparation coating solution
Blocker, plasticizer are soaked dissolving with wetting agent, leave standstill 10-12h, stir, obtain uniform and stable coating solution;
(32) coating
The pastille micropill is placed in the centrifugal coating pelletizing machine, engine speed 200-300rpm, air blast flux 10-20L/Min, jet flow 6-8L/min, whiff pressure 0.1-0.2MPa, 40-50 ℃ of inlet temperature, atomizing pressure is 0.1-0.2MPa; Start spray gun, the peristaltic pump rotating speed is 10-20rpm, sprays into coating solution to intact, pastille micropill behind the coating;
Annotate: in time be sprinkled into Pulvis Talci during coating to remove static, prevent adhesion;
(33) drying
Dry 10-15min under 50-60 ℃ of conditions, pastille micropill behind the taking-up coating; In 50 ℃, in basin, vulcanize 22-24h, it is that the pellet of 480-1700 μ m is target product that sieve is got granularity---the slow controlled release micro pill of Trimetazidine Hydrochloride.
The present invention can be used for preparing the slow controlled release micro pill of medicine Trimetazidine Hydrochloride, can be used for preparing pellet capsule, tablet and granule further.
Owing to adopted above-mentioned technical scheme, the present invention compared with prior art, obtained technological progress is:
⑴ micropill that centrifugal granulation is prepared size evenly, proper sphere degree height, good fluidity, be easy to handle;
⑵ when be equipped with micropill with this mechanism, the diversity between batch was little, and the repeatability of micropill preparation and coating process is better;
⑶ micropill belongs to multiple agent type, and the defective of indivedual micropills in preparation is unlikely to the drug release behavior generation of whole preparation is had a strong impact in the production process;
⑷ big at the gastrointestinal tract distribution area, the bioavailability height, and zest is little;
⑸ be not subjected to the gastric emptying factor affecting substantially, and the interior infiltration rate of the body of medicine is even and bioavailability among individuals difference is less;
⑹ micropill is wrapped up by slow release layer, also can not be affected as suppressing in flakes even change dosage form;
⑺ centrifugal granulator method can have been finished overall processes such as mother, medicine-feeding and last slow release layer in a closed system, thereby enhances productivity.
The present invention is described in further detail below in conjunction with specific embodiment.
The specific embodiment
Embodiment 1-5
Embodiment 1-5 is slow controlled release micro pill of a kind of Trimetazidine Hydrochloride and preparation method thereof, and the slow controlled release micro pill ball that each embodiment relates to directly is 480-1700um, and micropill pastille percentage rate is 5%-40%.
Related micropill shape structure comprises celphere, Trimetazidine Hydrochloride medicine layer, slow controlled release coat layer from the inside to the outside.
Make the celphere raw materials of effective components and comprise diluent, binding agent and wetting agent, wherein diluent is selected from a kind of in starch, sucrose, the microcrystalline Cellulose or at least two kinds mixture.
Make the coatings raw materials of effective components and comprise blocker, plasticizer and wetting agent, wherein plasticizer is selected from a kind of in dibutyl sebacate, triglyceride or the triethyl citrate; Blocker is a kind of in ethyl cellulose or the acrylic resin.
Binding agent is a kind of in hydroxypropyl methylcellulose or the polyvidone.
Wetting agent is 95% ethanol.
The concrete consumption of raw material of slow controlled release micro pill can be with reference to last table among the embodiment 1-5.
The slow controlled release micro pill of the Trimetazidine Hydrochloride that embodiment 1-5 is related, their preparation methoies separately, carry out according to the following steps order respectively:
1. the preparation of celphere: the celphere of preparation ball footpath 400-800 μ m
(11) preparation of one-level celphere
Pelletize: the powdery diluent of getting the above fineness of 100 orders; place on the centrifugal coating pelletizing machine rotating disk; starting device; engine speed 150-250rpm; air blast flux 6-20L/min, jet flow 6-20L/min, jet pressure 0.1MPa; spray into the mixed liquor of binding agent and wetting agent after the spray pattern, make pellet.(granulation process should note controlling the time of pelletize, and is excessive to prevent pill)
Sieve: the gained ball that sieves directly is the pellet of 400-800 μ m, can be directly as the one-level celphere, and standby;
(12) preparation of multistage celphere
The preparation of secondary celphere: the gained ball footpath of sieving, places on the centrifugal coating pelletizing machine rotating disk as the female ball of one-level less than the pellet of 400 μ m, and remaining diluent is put into powder feeder unit; Start centrifugal coating pelletizing machine, engine speed 150-250rpm, air blast flux 0-5L/min, jet flow 6-8L/min, jet pressure 0.1MPa sprays into the mixed liquor of binding agent and wetting agent after the spray pattern, to the female ball surface wettability of one-level, open powder feeder unit for powder, the female ball of one-level is constantly grown up, sieve get ball directly be the pellet of 400-800 μ m as the secondary celphere, standby;
The preparation of three grades of celphere: the gained ball footpath of sieving less than the pellet of 400 μ m as the female ball of secondary, place on the centrifugal coating pelletizing machine rotating disk, start centrifugal coating pelletizing machine, engine speed 150-250rpm, air blast flux 0-5L/min, jet flow 6-8L/min, jet pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, to the female ball surface wettability of secondary, open powder feeder unit for powder, the female ball of secondary is constantly grown up, sieve get ball directly be the pellet of 400-800 μ m as three grades of celphere, standby;
The preparation of level Four blank pill: the gained ball footpath of sieving less than the pellet of 400 μ m as three grades of female balls, place on the centrifugal coating pelletizing machine rotating disk, start centrifugal coating pelletizing machine, engine speed 150-250rpm, air blast flux 0-5L/min, jet flow 6-8L/min, jet pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, to three grades of female ball surface wettabilities, open powder feeder unit for powder, three grades of female balls are constantly grown up, sieve get ball directly be the pellet of 400-800 μ m as the level Four celphere, standby;
……
Repeat aforesaid operations, all be prepared as the celphere of ball footpath 400-800 μ m until all diluent.
2. prepare the pastille micropill: the mixed liquor of spray adhesive and wetting agent adheres to the celphere outer surface to the celphere surface wettability equably with medicine on celphere, makes the pastille micropill
Concrete operations are carried out according to the following steps order:
(21) spray binding agent
Celphere is placed centrifugal coating pelletizing machine, Trimetazidine Hydrochloride is put into powder feeder unit, start centrifugal coating pelletizing machine, engine speed 200-280rpm, air blast flux 0-5L/min, jet flow 6-8L/min, whiff pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, to the celphere surface wettability; Then,
(22) medicine-feeding
Open powder feeder unit and supply powder, wait for powder to finish, be dried to water content 2-3%, take out, sieve micropill after the medicine-feeding of getting 450-1000 μ m, be the pastille micropill.
3. coating prepares the purpose product: coat slow controlled-release material outside the pastille micropill, make target micropill product
Concrete operations are carried out according to the following steps order:
(31) preparation coating solution
Blocker, plasticizer are soaked dissolving with wetting agent, leave standstill 10-12h, stir, obtain uniform and stable coating solution;
(32) coating
The pastille micropill is placed in the centrifugal coating pelletizing machine, engine speed 200-300rpm, air blast flux 10-20L/min, jet flow 6-8L/min, whiff pressure 0.1-0.2MPa, inlet temperature is 40-50 ℃, atomizing pressure is 0.1-0.2MPa; Start spray gun, the peristaltic pump rotating speed is 10-20rpm, sprays into coating solution to intact, pastille micropill behind the coating; In time be sprinkled into Pulvis Talci in the coating process to remove static, prevent adhesion;
(33) drying
Dry 10-15min under 50-60 ℃ of conditions takes out pastille micropill behind the coating, vulcanizes 22-24h in 50 ℃ in basin, and it is that the pellet of 480-1700 μ m is target product that sieve is got granularity---beautiful his the slow controlled release micro pill of piperazine of salt love song.
Above-mentioned micropill directly becomes patent medicine through preparation process, promptly
4. preparation:,, make the dosage form that directly to take with the 3. slow controlled release micro pill of gained target product Trimetazidine Hydrochloride of step according to conventional method.
Particularly, embodiment 1-5 has made the patent medicine of three kinds of dosage forms respectively with the slow controlled release micro pill of prepared Trimetazidine Hydrochloride, and they are respectively:
A. directly pack as granule;
B. the encapsulated capsule of making;
C. make tablet through processing such as tablettings.
Claims (6)
1. the slow controlled release micro pill of a Trimetazidine Hydrochloride, it is characterized in that: this slow controlled release micro pill ball directly is 480-1700um, micropill shape structure comprises celphere, Trimetazidine Hydrochloride medicine layer, slow controlled release coat layer from the inside to the outside, and it is celphere 52-270 part, 20-40 parts of Trimetazidine Hydrochloride medicines, 5.5-120 parts on slow controlled release coat layer that their parts by weight close;
Make described celphere raw materials of effective components and comprise diluent, binding agent and wetting agent, wherein said diluent parts by weight are 50-240 parts, are selected from a kind of in starch, sucrose, the microcrystalline Cellulose or at least two kinds mixture;
Make described coatings raw materials of effective components and comprise blocker, plasticizer and wetting agent, wherein said blocker is a kind of in ethyl cellulose or the acrylic resin, and their parts by weight are respectively 6-60 parts, 8-90 parts; Described plasticizer is selected from a kind of in dibutyl sebacate, triglyceride or the triethyl citrate, and consumption is the 10-20% of blocker weight;
Described binding agent is a kind of in hydroxypropyl methylcellulose or the polyvidone, and used parts by weight are respectively 2-15 parts, 6-30 parts;
Described wetting agent is 95% ethanol, and its parts by weight are 200-3000 parts.
2. the preparation method of the slow controlled release micro pill of a Trimetazidine Hydrochloride as claimed in claim 1, it is characterized in that: described preparation method is carried out according to the following steps order:
1. the preparation of celphere: the celphere of preparation ball footpath 400-800 μ m;
2. prepare the pastille micropill: the mixed liquor of spray binding agent and wetting agent adheres to the celphere outer surface to the celphere surface wettability equably with medicine on celphere, makes the pastille micropill;
3. coating prepares the purpose product: coat slow controlled-release material outside the pastille micropill, make target micropill product.
3. according to the preparation method of the slow controlled release micro pill of right 2 described Trimetazidine Hydrochlorides, it is characterized in that: described step is the preparation of celphere 1., and concrete operations are carried out according to the following steps order:
(11) preparation of one-level celphere
Pelletize: the powdery diluent of getting the above fineness of 100 orders, be put on the centrifugal coating pelletizing machine rotating disk, starting device, engine speed 150-250rpm, air blast flux 6-20L/min, jet flow 6-20L/min, jet pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, make pellet;
Sieve: the gained ball that sieves directly is the pellet of 400-800 μ m, can be directly as the one-level celphere, and standby;
(12) preparation of multistage celphere
The preparation of secondary celphere: the gained ball footpath of sieving, is put on the centrifugal coating pelletizing machine rotating disk as the female ball of one-level less than the pellet of 400 μ m, and remaining diluent is put into powder feeder unit; Start centrifugal coating pelletizing machine, engine speed 150-250rpm, air blast flux 0-5L/min, jet flow 6-8L/min, jet pressure 0.1MPa sprays into the mixed liquor of binding agent and wetting agent after the spray pattern, to the female ball surface wettability of one-level, open powder feeder unit for powder, the female ball of one-level is constantly grown up, sieve get ball directly be the pellet of 400-800 μ m as the secondary celphere, standby;
The preparation of three grades of celphere: the gained ball footpath of sieving less than the pellet of 400 μ m as the female ball of secondary, be put on the centrifugal coating pelletizing machine rotating disk, start centrifugal coating pelletizing machine, engine speed 150-250rpm, air blast flux 0-5L/min, jet flow 6-8L/min, jet pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, to the female ball surface wettability of secondary, open powder feeder unit for powder, the female ball of secondary is constantly grown up, sieve get ball directly be the pellet of 400-800 μ m as three grades of celphere, standby;
The preparation of level Four blank pill: the gained ball footpath of sieving less than the pellet of 400 μ m as three grades of female balls, be put on the centrifugal coating pelletizing machine rotating disk, start centrifugal coating pelletizing machine, engine speed 150-250rpm, air blast flux 0-5L/min, jet flow 6-8L/min, jet pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, to three grades of female ball surface wettabilities, open powder feeder unit for powder, three grades of female balls are constantly grown up, sieve get ball directly be the pellet of 400-800 μ m as the level Four celphere, standby;
……
Repeat aforesaid operations, all be prepared as the celphere of ball footpath 400-800 μ m until all diluent.
4. according to the preparation method of the slow controlled release micro pill of right 2 described Trimetazidine Hydrochlorides, it is characterized in that: 2. described step prepares the pastille micropill, and concrete operations are carried out according to the following steps order:
(21) spray binding agent
Celphere is placed centrifugal coating pelletizing machine, Trimetazidine Hydrochloride is put into powder feeder unit, start centrifugal coating pelletizing machine, engine speed 200-280rpm, air blast flux 0-5L/min, jet flow 6-8L/min, whiff pressure 0.1MPa, spray into the mixed liquor of binding agent and wetting agent after the spray pattern, to the celphere surface wettability; Then,
(22) medicine-feeding
Open powder feeder unit and supply powder, wait for powder to finish, be dried to water content 2-3%, take out, sieve micropill after the medicine-feeding of getting 450-1000 μ m, be the pastille micropill.
5. according to the preparation method of the slow controlled release micro pill of right 2 described Trimetazidine Hydrochlorides, it is characterized in that: described step 3. coating prepares target product, and concrete operations are carried out according to the following steps order:
(31) preparation coating solution
Blocker, plasticizer are soaked dissolving with wetting agent, leave standstill 10-12h, stir, obtain uniform and stable coating solution;
(32) coating
The pastille micropill is placed in the centrifugal coating pelletizing machine, engine speed 200-300rpm, air blast flux 10-20L/min, jet flow 6-8L/min, whiff pressure 0.1-0.2MPa, inlet temperature is 40-50 ℃, atomizing pressure is 0.1-0.2MPa; Start spray gun, the peristaltic pump rotating speed is 10-20rpm, sprays into coating solution to intact, pastille micropill behind the coating;
Annotate: in time be sprinkled into Pulvis Talci during coating to remove static, prevent adhesion;
(33) drying
Dry 10-15min under 50-60 ℃ of conditions, pastille micropill behind the taking-up coating in 50 ℃, vulcanizes 22-24h in basin, and sieve is got the pellet that granularity is 480-1700 μ m, is target product---the controlled release micro pill that Trimetazidine Hydrochloride is slow.
6. according to the preparation method of the slow controlled release micro pill of claim 2 or 6 described Trimetazidine Hydrochlorides, it is characterized in that: described preparation method also is provided with the preparation step in step after 3. coating prepares target product, promptly
4. preparation
With the 3. slow controlled release micro pill of gained target product Trimetazidine Hydrochloride of step, make capsule, granule or tablet.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD20130005A2 (en) * | 2012-02-03 | 2013-07-31 | Les Laboratoires Servier | Pharmaceutical composition for prolonged release of trimetazidine |
| WO2015055130A3 (en) * | 2013-10-17 | 2015-06-18 | 广州帝奇医药技术有限公司 | Long-lasting, sustained-release micropellet and preparation method therefor |
| CN105148283A (en) * | 2015-09-28 | 2015-12-16 | 广东国源国药制药有限公司 | Innovative pharmaceutic adjuvant sucrose pill core and preparation method thereof |
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| US20130202710A1 (en) * | 2012-02-03 | 2013-08-08 | Les Laboratoires Servier | Pharmaceutical composition for the prolonged release of trimetazidine |
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| WO2015055130A3 (en) * | 2013-10-17 | 2015-06-18 | 广州帝奇医药技术有限公司 | Long-lasting, sustained-release micropellet and preparation method therefor |
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| 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 |
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| WO2019237446A1 (en) * | 2018-06-14 | 2019-12-19 | 深圳翰宇药业股份有限公司 | Trimetazidine sustained-release tablet and preparation method therefor |
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