CN102302469B - The preparation method of double layer osmotic pump controlled release felodipine sheet - Google Patents
The preparation method of double layer osmotic pump controlled release felodipine sheet Download PDFInfo
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- CN102302469B CN102302469B CN201110194686.9A CN201110194686A CN102302469B CN 102302469 B CN102302469 B CN 102302469B CN 201110194686 A CN201110194686 A CN 201110194686A CN 102302469 B CN102302469 B CN 102302469B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 title claims abstract description 24
- 229960003580 felodipine Drugs 0.000 title claims abstract description 24
- 238000013270 controlled release Methods 0.000 title claims abstract description 12
- 230000003204 osmotic effect Effects 0.000 title abstract description 9
- 239000011248 coating agent Substances 0.000 claims abstract description 53
- 238000000576 coating method Methods 0.000 claims abstract description 53
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 28
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 13
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 10
- 229920002472 Starch Polymers 0.000 claims abstract description 10
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 10
- 239000011734 sodium Substances 0.000 claims abstract description 10
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 10
- 239000008107 starch Substances 0.000 claims abstract description 10
- 235000019698 starch Nutrition 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 239000011780 sodium chloride Substances 0.000 claims abstract description 5
- 239000008187 granular material Substances 0.000 claims description 42
- 230000001476 alcoholic effect Effects 0.000 claims description 26
- 238000002156 mixing Methods 0.000 claims description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- 239000007779 soft material Substances 0.000 claims description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 13
- 239000000741 silica gel Substances 0.000 claims description 13
- 229910002027 silica gel Inorganic materials 0.000 claims description 13
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 12
- 229920003081 Povidone K 30 Polymers 0.000 claims description 12
- 229920003082 Povidone K 90 Polymers 0.000 claims description 10
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 229920002301 cellulose acetate Polymers 0.000 claims description 8
- 239000012530 fluid Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 239000007888 film coating Substances 0.000 claims description 7
- 238000009501 film coating Methods 0.000 claims description 7
- 238000005553 drilling Methods 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 230000005070 ripening Effects 0.000 claims description 6
- 230000004584 weight gain Effects 0.000 claims description 6
- 235000019786 weight gain Nutrition 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims 3
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 5
- 239000004014 plasticizer Substances 0.000 abstract description 2
- 239000003361 porogen Substances 0.000 abstract description 2
- 239000012528 membrane Substances 0.000 abstract 2
- 239000003814 drug Substances 0.000 description 11
- 239000003826 tablet Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 206010020772 Hypertension Diseases 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 4
- 239000010408 film Substances 0.000 description 4
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- -1 dipicolinic acid ethyl ester methyl ester Chemical class 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229940127088 antihypertensive drug Drugs 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- RZTAMFZIAATZDJ-UHFFFAOYSA-N felodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-UHFFFAOYSA-N 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229940090013 plendil Drugs 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- WJJMNDUMQPNECX-UHFFFAOYSA-N Dipicolinic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 239000000219 Sympatholytic Substances 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- ASCWBYZMMHUZMQ-UHFFFAOYSA-N bis(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCCOCCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCOCCC)C1C1=CC=CC=C1OC(F)F ASCWBYZMMHUZMQ-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000013563 matrix tablet Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 230000008327 renal blood flow Effects 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000000948 sympatholitic effect Effects 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention provides a kind of felodipine double-layer osmotic pump-type controlled release tablet preparation method, be made up of double-deck label and the semi-transparent coating membrane of controlled release, composition label comprises pharmaceutically acceptable excipient: copolyvidone, carboxymethyl starch sodium, sodium chloride, magnesium stearate, iron oxide red, iron oxide yellow etc.; The semi-transparent coating membrane of controlled release by filmogen, porogen, plasticizer one or more form.Felodipine controlled release tablet of the present invention, with controlled speed release felodipine, makes preparation reach daily object once.
Description
One, technical field
The present invention relates to field of pharmaceutical preparations, especially to the preparation method that a kind of antihypertensive drug felodipine adopts copolyvidone, carboxymethyl starch sodium is the osmotic pump type drug-delivery preparation of main carriers and excipient.
Two, background technology
Felodipine (Felodipine, chemical name is: 4-(2,3 Dichlorobenzene base)-1,4-dihydro-2,6-dimethyl-3 dipicolinic acid ethyl ester methyl ester), be selectivity cerebrocrast, the interior stream of the outer calcium of main suppression small artery smooth muscle cell, selectivity expansion small artery, acts on without this vein, does not cause postural hypotension; To cardiac muscle also without obvious inhibitory action.Felodipine is while reduction renal vascular resistance, and do not affect glomerular filtration rate and creatinine clearance rate, renal blood flow is unchanged even to be had increased slightly, and has short natruresis and diuresis.Output and cardiac index can be increased, significantly reduce afterload, and cardiac systolic function, preload and heart rate are had no significant effect, be applicable to treatment that is light, Moderate Essential Hypertension.
Hypertension is one of modal cardiovascular disease in the world today, is also the Major Risk Factors of cardiovascular and cerebrovascular disease.Epidemiological study shows, and there is hyperpietic 600,000,000 people in the current whole world, and Prevalence of Hypertension is about 10%, and more American-European developed countries are 20%.China's Prevalence of Hypertension is about 12%, and existing hyperpietic's number is more than 100,000,000 people, and annual with the speed increment of 3,000,000 people.Currently to be divided into diuretic, beta-blocker, calcium ion antagonist for antihypertensive drug main, act on several large classes such as renin-angiotensin system medicine, sympatholytic.Wherein, calcium ion antagonist, as the status of resisting hypertension first-line drug, all obtains in European hypertension prevention and control guide certainly WHO/ISH hypertension prevention and control guides in 1999 and 2003.
At present, the product at home and abroad gone on the market is Astrazeneca AB's " Plendil; Plendil ", it is a kind of gel matrix tablet adopting Polymer materialspreparation, medicine enters swelling formation gel after in body, and continuous corrosion, discharges medicine slowly, this type of preparation, due to self open oral slow-releasing preparation feature, is subject to the impact of Different Individual fluid environment.The drug release behavior of Oros preparation is not by the impact of gastrointestinal tract pH value, gastrointestinal peristalsis, and have In vitro-in vivo correlation high, individual variation affects little feature.The carrier that the osmotic pump preparation (ZL200610103992.6) of current felodipine adopts is polyoxyethylene, and its surfactant adding larger proportion in prescription is as solubility improving substances, polyoxyethylene is adopted to be time lag and the poor heat stability (glass transformation temperature is 65 ~ 67 DEG C) that osmotic pump preparation prepared by carrier has the long period, unfavorable rapid performance with drug effect and suitability for industrialized production; The adding of surfactant of larger proportion reduces the safety of medication and the stability of tablet.
Three, summary of the invention
The object of the present invention is to provide a kind of containing active medicine felodipine, with the osmotic pump type drug-delivery preparation that copolyvidone, carboxymethyl starch sodium are main carriers and excipient, it is long that said preparation has shorter time lag, effectively persistent period, can reach better controlled-release effect, the product of preparation is convenient to produce, be easy to store.
The present invention does not adopt the method for surface active agent solubilization for insoluble drug felodipine, and the product of preparation is more safely with stable.
Felodipine osmotic pump preparation provided by the invention, wherein comprise the label that weight ratio is 1: 0.5 ~ 1.0 medicated layer and boosting layer composition, its surface is surrounded by the thin film of semipermeable materials, makes a call to an aperture in medicated layer side.
Medicated layer of the present invention or boosting layer are by pharmaceutically acceptable excipient: copolyvidone, carboxymethyl starch sodium, iron oxide red, iron oxide yellow, sodium chloride, polyvinylpyrrolidone, magnesium stearate, micropowder silica gel one or more form; Controlled release coat film to the liquid property of can pass through in gastrointestinal tract, by filmogen, porogen, plasticizer one or more form, mainly include but not limited to cellulose acetate, Polyethylene Glycol.
The film coating weightening finish of described semipermeable materials is 5% ~ 15% of label weight.Described medicated layer one side surface small delivery aperture is beaten by laser, and pore size is 0.5 to 1.0mm.Its active component of felodipine osmotic pump tablet prepared for the present invention and excipient form by following proportioning:
(1) medicated layer
Soft material is prepared with the polyvinylpyrrolidone alcoholic solution of 10%.
(2) boosting layer
Soft material is prepared with the polyvinylpyrrolidone alcoholic solution of 10%.
(3) coating fluid prescription
Cellulose acetate 15%-40%
Polyethylene Glycol 1%-20%
Acetone in proper
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3% ~ 5%
Four, accompanying drawing illustrates:
Fig. 1: the embodiment of the present invention 1 Accumulation dissolution.
Fig. 2: the embodiment of the present invention 1 cumulative release speed.
Fig. 3: the embodiment of the present invention 2 Accumulation dissolution.
Fig. 4: the embodiment of the present invention 2 cumulative release speed.
Fig. 5: the embodiment of the present invention 3 Accumulation dissolution.
Fig. 6: the embodiment of the present invention 3 cumulative release speed.
Five, detailed description of the invention
Below set forth and describe the present invention in detail, but do not limit institute of the present invention practical range.
Embodiment 1
(1) medicated layer
Soft material is prepared with the PVP-K90 alcoholic solution of 10%.
(2) boosting layer
Soft material is prepared with the PVP-K30 alcoholic solution of 10%.
Make 1000 altogether.
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone in proper
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%
Preparation method:
1. the preparation of medicated layer granule:
By felodipine and PLASDONES630, cross 200 mesh sieves, add iron oxide yellow, mixing, the PVP-K90 alcoholic solution with 10% is granulated, and cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains medicated layer granule.
2. the preparation of boosting layer granule:
Carboxymethyl starch sodium, NaCL are ground into fine powder, cross 200 mesh sieves, add iron oxide red, mixing, granulate with 10%PVP-K30 alcoholic solution, cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains boosting layer granule.
3. tabletting:
Adopt bi-layer tablet press compacting double-layer tablet, sheet footpath is 8mm, measures hardness, content and the uniformity.
4. release-controlled film coating and laser boring:
The label of above-mentioned preparation is adopted the coating solution coating prepared, the product after coating is ripening 6h at 45 DEG C, adopts laser-beam drilling machine on the film of medicated layer side, punch the aperture that footpath is 0.8mm.
5. pack moistureproof clothing:
Adopt Opadry xy type coating solution to pack moistureproof clothing, controlling coating weight gain is 3%.
6. drug release determination method
According to Chinese Pharmacopoeia version in 2010 two annex XD first methods, the device of dissolution determination method first method is adopted to determine the vitro release of felodipine controlled release tablet prepared by embodiment 1, rotating speed is 100r/min, (the sodium dihydrogen phosphate 206ml of 1mol/L is got with 0.4% cetyl trimethyl ammonium bromide PH6.5 phosphate buffer, the disodium phosphate soln 196ml of 0.5mol/L, cetyl trimethyl ammonium bromide 20g, adding water to 5000ml) 500ml is release medium, temperature is 37 DEG C, stripping rotor put into by tablet, respectively 2, 4, 6, 8, 10, 12, 16, 20, 24h samples 5ml, add 0.4% cetyl trimethyl ammonium bromide PH6.5 phosphate buffer of equality of temperature same volume simultaneously.
Embodiment 2
(1) medicated layer
Soft material is prepared with the PVP-K30 alcoholic solution of 10%.
(2) boosting layer
Soft material is prepared with the PVP-K90 alcoholic solution of 10%.
Make 1000 altogether.
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone in proper
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%
Preparation method:
1. the preparation of medicated layer granule:
By felodipine and PLASDONES630, cross 200 mesh sieves, add iron oxide yellow, mixing, the PVP-K30 alcoholic solution with 10% is granulated, and cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains medicated layer granule.
2. the preparation of boosting layer granule:
Carboxymethyl starch sodium, NaCL are ground into fine powder, cross 200 mesh sieves, add iron oxide red, mixing, granulate with 10%PVP-K90 alcoholic solution, cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains boosting layer granule.
2. tabletting:
Adopt bi-layer tablet press compacting double-layer tablet, sheet footpath is 8mm, measures hardness, content and the uniformity.
4. release-controlled film coating and laser boring:
The label of above-mentioned preparation is adopted the coating solution coating prepared, the product after coating is ripening 6h at 45 DEG C, adopts laser-beam drilling machine on the film of medicated layer side, punch the aperture that footpath is 0.6mm.
5. pack moistureproof clothing:
Adopt Opadry xy type coating solution to pack moistureproof clothing, controlling coating weight gain is 3%.
6. drug release determination method
With embodiment 1.
Embodiment 3
(1) medicated layer
Soft material is prepared with the alcoholic solution of 95%.
(2) boosting layer
Soft material is prepared with the PVP-K30 alcoholic solution of 10%.
Make 1000 altogether.
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone in proper
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%
Preparation method:
1. the preparation of medicated layer granule:
By felodipine and PVP-K90, PLASDONES630, cross 200 mesh sieves, add iron oxide yellow, mixing, the alcoholic solution with 95% is granulated, and cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains medicated layer granule.
2. the preparation of boosting layer granule:
Carboxymethyl starch sodium, NaCL are ground into fine powder, cross 200 mesh sieves, add iron oxide red, mixing, granulate with 10%PVP-K30 alcoholic solution, cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains boosting layer granule.
3. tabletting:
Adopt bi-layer tablet press compacting double-layer tablet, sheet footpath is 8mm, measures hardness, content and the uniformity.
4. release-controlled film coating and laser boring:
The label of above-mentioned preparation is adopted the coating solution coating prepared, the product after coating is ripening 6h at 45 DEG C, adopts laser-beam drilling machine on the film of medicated layer side, punch the aperture that footpath is 0.8mm.
5. pack moistureproof clothing:
Adopt Opadry xy type coating solution to pack moistureproof clothing, controlling coating weight gain is 3%.
6. drug release determination method
With embodiment 1.
Claims (3)
1. a felodipine controlled release formulation, is characterized in that, preparation method is as follows:
(1) medicated layer
Soft material is prepared with the PVP-K90 alcoholic solution of 10%;
(2) boosting layer
Soft material is prepared with the PVP-K30 alcoholic solution of 10%;
Make 1000 altogether;
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone in proper
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%;
The preparation of medicated layer granule:
By felodipine and PLASDONES630, cross 200 mesh sieves, add iron oxide yellow, mixing, the PVP-K90 alcoholic solution with 10% is granulated, and cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains medicated layer granule;
The preparation of boosting layer granule:
Carboxymethyl starch sodium, NaCl are ground into fine powder, cross 200 mesh sieves, add iron oxide red, mixing, granulate with 10%PVP-K30 alcoholic solution, cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains boosting layer granule;
Tabletting:
Adopt bi-layer tablet press compacting double-layer tablet, sheet footpath is 8mm, measures hardness, content and the uniformity;
Release-controlled film coating and laser boring:
The coating solution coating adopting (3) to prepare the label of above-mentioned preparation, the product after coating is ripening 6h at 45 DEG C, adopts laser-beam drilling machine on the film of medicated layer side, punch the aperture that footpath is 0.8mm;
Pack moistureproof clothing:
Adopt Opadry xy type coating solution to pack moistureproof clothing, controlling coating weight gain is 3%.
2. a felodipine controlled release formulation, is characterized in that, preparation method is as follows:
(1) medicated layer
Soft material is prepared with the PVP-K30 alcoholic solution of 10%;
(2) boosting layer
Soft material is prepared with the PVP-K90 alcoholic solution of 10%;
Make 1000 altogether;
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone in proper
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%;
The preparation of medicated layer granule:
By felodipine and PLASDONES630, cross 200 mesh sieves, add iron oxide yellow, mixing, the PVP-K30 alcoholic solution with 10% is granulated, and cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains medicated layer granule;
The preparation of boosting layer granule:
Carboxymethyl starch sodium, NaCl are ground into fine powder, cross 200 mesh sieves, add iron oxide red, mixing, granulate with 10%PVP-K90 alcoholic solution, cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains boosting layer granule;
Tabletting:
Adopt bi-layer tablet press compacting double-layer tablet, sheet footpath is 8mm, measures hardness, content and the uniformity;
Release-controlled film coating and laser boring:
The coating solution coating adopting (3) to prepare the label of above-mentioned preparation, the product after coating is ripening 6h at 45 DEG C, adopts laser-beam drilling machine on the film of medicated layer side, punch the aperture that footpath is 0.6mm;
Pack moistureproof clothing:
Adopt Opadry xy type coating solution to pack moistureproof clothing, controlling coating weight gain is 3%.
3. a felodipine controlled release formulation, is characterized in that, preparation method is as follows:
(1) medicated layer
Soft material is prepared with the alcoholic solution of 95%;
(2) boosting layer
Soft material is prepared with the PVP-K30 alcoholic solution of 10%;
Make 1000 altogether;
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone in proper
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%;
The preparation of medicated layer granule:
By felodipine and PVP-K90, PLASDONES630, cross 200 mesh sieves, add iron oxide yellow, mixing, the alcoholic solution with 95% is granulated, and cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains medicated layer granule;
The preparation of boosting layer granule:
Carboxymethyl starch sodium, NaCl are ground into fine powder, cross 200 mesh sieves, add iron oxide red, mixing, granulate with 10%PVP-K30 alcoholic solution, cross 40 mesh sieves and granulate, 50 DEG C of dry 12h, add magnesium stearate, micropowder silica gel, and mixing, obtains boosting layer granule;
Tabletting:
Adopt bi-layer tablet press compacting double-layer tablet, sheet footpath is 8mm, measures hardness, content and the uniformity;
Release-controlled film coating and laser boring:
The coating solution coating adopting (3) to prepare the label of above-mentioned preparation, the product after coating is ripening 6h at 45 DEG C, adopts laser-beam drilling machine on the film of medicated layer side, punch the aperture that footpath is 0.8mm;
Pack moistureproof clothing:
Adopt Opadry xy type coating solution to pack moistureproof clothing, controlling coating weight gain is 3%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| CN1931167A (en) * | 2006-06-28 | 2007-03-21 | 广州贝氏药业有限公司 | Double layer osmotic pump controlled release felodipine medicine composition |
| CN101161242A (en) * | 2006-10-13 | 2008-04-16 | 北京红林制药有限公司 | A explosive core composition of controlled release administer drug and controlled release preparation as well as its preparing method |
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| US6764697B1 (en) * | 1991-06-27 | 2004-07-20 | Alza Corporation | System for delaying drug delivery up to seven hours |
| CN1270712C (en) * | 2004-01-08 | 2006-08-23 | 曹德英 | Felodipine controlled-release preparation |
| US20070098791A1 (en) * | 2005-10-31 | 2007-05-03 | Rekhi Gurvinder S | Controlled release compositions comprising a combination of isosorbide dinitrate and hydralazine hydrochloride |
| CN100350909C (en) * | 2006-02-27 | 2007-11-28 | 合肥立方制药有限公司 | Method for preparing insoluble drug single-tablet-core single-chamber osmotic pump sustained-release preparations and its product |
| KR100841877B1 (en) * | 2006-08-31 | 2008-06-27 | 조선대학교산학협력단 | Locally solubilized controlled release matrix tablet of poorly soluble drugs |
| CN101292962B (en) * | 2007-04-26 | 2012-05-23 | 杭州民生药业有限公司 | Felodipine controlled release formulation and preparation method thereof |
| JP2011500605A (en) * | 2007-10-16 | 2011-01-06 | アルファファーム ピーティーワイ リミテッド | Controlled release pharmaceutical formulation |
| CN101879146A (en) * | 2009-05-08 | 2010-11-10 | 广州柏赛罗药业有限公司 | Controlled release preparation and preparation method thereof |
| CN101856337B (en) * | 2010-05-28 | 2012-10-03 | 中国科学院上海药物研究所 | Novel penetration and controlled-release medicament delivery system and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1931167A (en) * | 2006-06-28 | 2007-03-21 | 广州贝氏药业有限公司 | Double layer osmotic pump controlled release felodipine medicine composition |
| CN101161242A (en) * | 2006-10-13 | 2008-04-16 | 北京红林制药有限公司 | A explosive core composition of controlled release administer drug and controlled release preparation as well as its preparing method |
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Denomination of invention: Preparation method of felodipine double-layer osmotic pump controlled release tablets Effective date of registration: 20231228 Granted publication date: 20160106 Pledgee: China Construction Bank Corporation Hefei Shushan sub branch Pledgor: HEFEI HUAFANG PHARMACEUTICAL SCIENCES & TECHNOLOGY Co.,Ltd. Registration number: Y2023980075424 |
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