CN102302469A - Preparation method of felodipine two-layer osmotic pump controlled release tablet - Google Patents
Preparation method of felodipine two-layer osmotic pump controlled release tablet Download PDFInfo
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- CN102302469A CN102302469A CN201110194686A CN201110194686A CN102302469A CN 102302469 A CN102302469 A CN 102302469A CN 201110194686 A CN201110194686 A CN 201110194686A CN 201110194686 A CN201110194686 A CN 201110194686A CN 102302469 A CN102302469 A CN 102302469A
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- felodipine
- layer
- controlled release
- preparation
- tablet
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- 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 19
- 229960003580 felodipine Drugs 0.000 title claims abstract description 19
- 238000013270 controlled release Methods 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title abstract description 25
- 230000003204 osmotic effect Effects 0.000 title abstract description 9
- 239000011248 coating agent Substances 0.000 claims abstract description 32
- 238000000576 coating method Methods 0.000 claims abstract description 32
- 239000000463 material Substances 0.000 claims abstract description 7
- 230000001476 alcoholic effect Effects 0.000 claims description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- 239000007779 soft material Substances 0.000 claims description 10
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- 229920002301 cellulose acetate Polymers 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- 239000007888 film coating Substances 0.000 claims description 5
- 238000009501 film coating Methods 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 239000010409 thin film Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 abstract description 16
- 235000019359 magnesium stearate Nutrition 0.000 abstract description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 7
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 abstract description 7
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 5
- 239000011780 sodium chloride Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 2
- 230000003203 everyday effect Effects 0.000 abstract 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N ferric oxide Chemical compound O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 abstract 1
- 229960005191 ferric oxide Drugs 0.000 abstract 1
- 229940051164 ferric oxide yellow Drugs 0.000 abstract 1
- 229940057948 magnesium stearate Drugs 0.000 abstract 1
- 229960002668 sodium chloride Drugs 0.000 abstract 1
- 229940080313 sodium starch Drugs 0.000 abstract 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 16
- 238000000034 method Methods 0.000 description 15
- 239000008187 granular material Substances 0.000 description 12
- 238000002156 mixing Methods 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- 239000003826 tablet Substances 0.000 description 10
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 206010020772 Hypertension Diseases 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- 229920003081 Povidone K 30 Polymers 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 230000001186 cumulative effect Effects 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 229920003082 Povidone K 90 Polymers 0.000 description 5
- 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
- 229920003072 Plasdone™ povidone Polymers 0.000 description 3
- -1 dipicolinic acid ethyl ester methyl ester Chemical class 0.000 description 3
- 238000005553 drilling Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000005070 ripening Effects 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
- 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
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229940090013 plendil Drugs 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- 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
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 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
- 229940117389 dichlorobenzene 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
- 238000004090 dissolution Methods 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
- 238000000338 in vitro 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
- 230000035699 permeability Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000003361 porogen Substances 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
- 239000000126 substance Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000000948 sympatholitic effect Effects 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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Abstract
The invention provides a preparation method of felodipine two-layer osmotic pump controlled release tablet, consisting of a two-layer tablet core and a controlled release semipermeable coating film. The tablet core comprises pharmaceutically acceptable excipients including: Sunvidone VA, sodium starch carboxymethyl, sodium chloride, magnesium stearate, ferric oxide red, ferric oxide yellow and the like; the controlled release semipermeable coating film is composed of one or several kinds of film-forming material, porogenic agent and plasticizing agent. The felodipine controlled release tablet prepared by the invention releases felodipine at a controlled speed, so that the purpose of one-time administration for every day when using the tablet can be achieved.
Description
One, technical field
The present invention relates to field of pharmaceutical preparations, especially a kind of antihypertensive drug felodipine being adopted copolyvidone, carboxymethyl starch sodium is the method for preparing of the osmotic pump type drug-delivery preparation of main carrier 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 the selectivity cerebrocrast; The main interior stream that suppresses the outer calcium of small artery smooth muscle cell; Selectivity expansion small artery does not have this effect to vein, does not cause postural hypotension; Cardiac muscle also there is not obvious inhibitory action.Felodipine does not influence glomerular filtration rate and creatinine clearance rate when reducing renal vascular resistance, renal blood flow no change even increase is arranged slightly has short natruresis and diuresis.Can increase output and cardiac index, significantly reduce afterload, and cardiac systolic function, preload and heart rate are not had obvious influence, be applicable to treatment light, the moderate essential hypertension.
Hypertension is one of modal cardiovascular disease in the world today, also is the main hazard factor of cardiovascular and cerebrovascular disease.Epidemiological study shows that there are hyperpietic 600,000,000 people in the whole world at present, and the hypertension prevalence is about 10%, and more American-European developed countries are 20%.China's hypertension prevalence is about 12%, and existing hyperpietic's number surpasses 100,000,000 people, and annual speed increment with 3,000,000 people.Currently be used for that antihypertensive drug main will be divided into diuretic, beta-blocker, calcium ion antagonist, to act on renin-angiotensin system medicine, sympatholytic etc. several big type.Wherein, calcium ion antagonist is as the status of resisting hypertension one line medicine, at WHO/ISH hypertension prevention and control guides in 1999 with all obtained in the European hypertension prevention and control guide in 2003 certainly.
At present; At home and abroad Shang Shi product is Astrazeneca AB's " Plendil; Plendil "; It is a kind of gel matrix tablet of adopting the macromolecular material preparation; Medicine gets into back swelling formation gel in the body, and constantly corrosion discharges medicine slowly; This type of preparation is subject to the influence of Different Individual body fluid environment owing to self open oral slow-releasing preparation characteristic.The drug release behavior of Oros preparation is not subjected to the influence of gastrointestinal tract pH value, gastrointestinal peristalsis, has inside and outside dependency height, the characteristics that the individual variation influence is little.The carrier of the osmotic pump preparation (ZL200610103992.6) of felodipine employing at present is a polyoxyethylene; And its surfactant that in prescription, has added larger proportion is as the hydrotropy material; Adopting polyoxyethylene is that the osmotic pump preparation of preparing carriers has the time lag of long period and relatively poor heat stability (glass transformation temperature is 65～67 ℃), the rapid performance and the suitability for industrialized production of unfavorable and drug effect; The adding of the surfactant of larger proportion has reduced 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 active medicine felodipine that contains; With copolyvidone, carboxymethyl starch sodium is the osmotic pump type drug-delivery preparation of main carrier and excipient; Said preparation has short time lag, effective longer duration; Can reach better controlled-release effect, the product of preparation is convenient to produce, is easy to store.
The present invention does not adopt the method for surface active agent solubilization for the insoluble drug felodipine, the product of preparation more safety with stable.
Felodipine osmotic pump preparation provided by the invention, wherein comprising weight ratio is the label that 1: 0.5～1.0 medicated layer and boosting layer are formed, its surface is surrounded by the thin film of semipermeable materials, makes a call to an aperture in medicated layer one side.
Medicated layer of the present invention or boosting layer are by pharmaceutically acceptable excipient: one or more of copolyvidone, carboxymethyl starch sodium, iron oxide red, iron oxide yellow, sodium chloride, polyvinylpyrrolidone, magnesium stearate, micropowder silica gel are formed; But the controlled release coat film is a permeability to the liquid in the gastrointestinal tract, is made up of one or more of filmogen, porogen, plasticizer, mainly includes 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 and the excipient that are used for the present invention's preparation are formed by following proportioning:
(1) medicated layer
Polyvinylpyrrolidone alcoholic solution with 10% prepares soft material.
(2) boosting layer
Polyvinylpyrrolidone alcoholic solution with 10% prepares soft material.
(3) coating fluid prescription
Cellulose acetate 15%-40%
Acetone is an amount of
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%～5%
Four, description of drawings:
Fig. 1: the embodiment of the invention 1 cumulative release degree.
Fig. 2: the embodiment of the invention 1 cumulative release speed.
Fig. 3: the embodiment of the invention 2 cumulative release degree.
Fig. 4: the embodiment of the invention 2 cumulative release speed.
Fig. 5: the embodiment of the invention 3 cumulative release degree.
Fig. 6: the embodiment of the invention 3 cumulative release speed.
Five, the specific embodiment
Below set forth and describe the present invention in detail, but do not limit institute of the present invention practical range.
(1) medicated layer
PVP-K90 alcoholic solution with 10% prepares soft material.
(2) boosting layer
PVP-K30 alcoholic solution with 10% prepares soft material.
Process 1000 altogether.
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone is an amount of
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%
Method for preparing:
1. the particulate preparation of medicated layer:
With felodipine and PLASDONE S630, cross 200 mesh sieves, add iron oxide yellow, mixing, the PVP-K90 alcoholic solution with 10% is granulated, and crosses 40 mesh sieves and granulates, 50 ℃ of dry 12h add magnesium stearate, micropowder silica gel, mixing, the medicated layer granule.
2. the particulate preparation of boosting layer:
Carboxymethyl starch sodium, NaCL are ground into fine powder, cross 200 mesh sieves, add iron oxide red, mixing is granulated with the 10%PVP-K30 alcoholic solution, crosses 40 mesh sieves and granulates, and 50 ℃ of dry 12h add magnesium stearate, micropowder silica gel, mixing, boosting layer granule.
3. tabletting:
Adopt bi-layer tablet press compacting double-layer tablet, sheet directly 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 for preparing, and the product behind the coating adopts laser-beam drilling machine on the film of medicated layer one side, to make a call to the aperture that an aperture is 0.8mm at 45 ℃ of following ripening 6h.
5. pack moistureproof clothing:
Adopt Opadry xy type coating solution to pack moistureproof clothing, the weightening finish of control coating is 3%.
6. drug release determination method
According to two appendix XD first methods of Chinese Pharmacopoeia version in 2010; The device of employing dissolution determination method first method has been measured the release in vitro degree of the felodipine controlled release tablet of embodiment 1 preparation; Rotating speed is 100r/min; (get the sodium dihydrogen phosphate 206ml of 1mol/L with 0.4% cetyl trimethyl ammonium bromide PH6.5 phosphate buffer; 0.5mol/L disodium phosphate soln 196ml; Cetyl trimethyl ammonium bromide 20g; Adding water to 5000ml) 500ml is release medium; Temperature is 37 ℃; Tablet is put into stripping rotor; Respectively 2; 4; 6; 8; 10; 12; 16; 20; The 24h 5ml that takes a sample adds the 0.4% cetyl trimethyl ammonium bromide PH6.5 phosphate buffer of equality of temperature with volume simultaneously.
(1) medicated layer
PVP-K30 alcoholic solution with 10% prepares soft material.
(2) boosting layer
PVP-K90 alcoholic solution with 10% prepares soft material.
Process 1000 altogether.
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone is an amount of
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%
Method for preparing:
1. the particulate preparation of medicated layer:
With felodipine and PLASDONE S630, cross 200 mesh sieves, add iron oxide yellow, mixing, the PVP-K30 alcoholic solution with 10% is granulated, and crosses 40 mesh sieves and granulates, 50 ℃ of dry 12h add magnesium stearate, micropowder silica gel, mixing, the medicated layer granule.
2. the particulate preparation of boosting layer:
Carboxymethyl starch sodium, NaCL are ground into fine powder, cross 200 mesh sieves, add iron oxide red, mixing is granulated with the 10%PVP-K90 alcoholic solution, crosses 40 mesh sieves and granulates, and 50 ℃ of dry 12h add magnesium stearate, micropowder silica gel, mixing, boosting layer granule.
2. tabletting:
Adopt bi-layer tablet press compacting double-layer tablet, sheet directly 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 for preparing, and the product behind the coating adopts laser-beam drilling machine on the film of medicated layer one side, to make a call to the aperture that an aperture is 0.6mm at 45 ℃ of following ripening 6h.
5. pack moistureproof clothing:
Adopt Opadry xy type coating solution to pack moistureproof clothing, the weightening finish of control coating is 3%.
6. drug release determination method
With embodiment 1.
(1) medicated layer
Alcoholic solution with 95% prepares soft material.
(2) boosting layer
PVP-K30 alcoholic solution with 10% prepares soft material.
Process 1000 altogether.
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone is an amount of
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%
Method for preparing:
1. the particulate preparation of medicated layer:
With felodipine and PVP-K90, PLASDONE S630, cross 200 mesh sieves, add iron oxide yellow, mixing, the alcoholic solution with 95% is granulated, and crosses 40 mesh sieves and granulates, 50 ℃ of dry 12h add magnesium stearate, micropowder silica gel, mixing, the medicated layer granule.
2. the particulate preparation of boosting layer:
Carboxymethyl starch sodium, NaCL are ground into fine powder, cross 200 mesh sieves, add iron oxide red, mixing is granulated with the 10%PVP-K30 alcoholic solution, crosses 40 mesh sieves and granulates, and 50 ℃ of dry 12h add magnesium stearate, micropowder silica gel, mixing, boosting layer granule.
3. tabletting:
Adopt bi-layer tablet press compacting double-layer tablet, sheet directly 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 for preparing, and the product behind the coating adopts laser-beam drilling machine on the film of medicated layer one side, to make a call to the aperture that an aperture is 0.8mm at 45 ℃ of following ripening 6h.
5. pack moistureproof clothing:
Adopt Opadry xy type coating solution to pack moistureproof clothing, the weightening finish of control coating is 3%.
6. drug release determination method
With embodiment 1.
Claims (3)
1. felodipine controlled release formulation, wherein comprising weight ratio is the label that 1: 0.5～1.0 medicated layer and boosting layer are formed, its surface is surrounded by the thin film of semipermeable materials, it is characterized in that, forms 1000 consist of:
(1) medicated layer
Polyvinylpyrrolidone alcoholic solution with 10% prepares soft material.
(2) boosting layer
Polyvinylpyrrolidone alcoholic solution with 10% prepares soft material.
(3) coating fluid prescription
Cellulose acetate 60g
Polyethylene Glycol 5g
Acetone is an amount of
(4) moistureproof coating liquid prescription
Opadry xy type coating solution 3%～5%
2. the weightening finish of the film coating of the described semipermeable materials of claim 1 is 5%～15% of label weight.
3. adopt the laser boring mode to make a call to the circular aperture of one 0.5～1.0mm in medicated layer one side.
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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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