CN1091600C - Process for preparing controlled-release tablet of diltiazem hydrochloride - Google Patents
Process for preparing controlled-release tablet of diltiazem hydrochloride Download PDFInfo
- Publication number
- CN1091600C CN1091600C CN 95111600 CN95111600A CN1091600C CN 1091600 C CN1091600 C CN 1091600C CN 95111600 CN95111600 CN 95111600 CN 95111600 A CN95111600 A CN 95111600A CN 1091600 C CN1091600 C CN 1091600C
- Authority
- CN
- China
- Prior art keywords
- diltiazem hydrochloride
- controlled release
- lubricant
- release tablet
- hours
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- FEDJGPQLLNQAIY-UHFFFAOYSA-N 2-[(6-oxo-1h-pyridazin-3-yl)oxy]acetic acid Chemical compound OC(=O)COC=1C=CC(=O)NN=1 FEDJGPQLLNQAIY-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 229960005316 diltiazem hydrochloride Drugs 0.000 title claims abstract description 46
- 238000013270 controlled release Methods 0.000 title claims abstract description 40
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 18
- 239000000463 material Substances 0.000 claims description 29
- 239000000314 lubricant Substances 0.000 claims description 16
- 239000010408 film Substances 0.000 claims description 12
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 12
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 12
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 11
- 239000000945 filler Substances 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 239000004014 plasticizer Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 8
- 235000021355 Stearic acid Nutrition 0.000 claims description 8
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical group CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 8
- 230000002209 hydrophobic effect Effects 0.000 claims description 8
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 8
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 8
- 239000008117 stearic acid Substances 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 7
- 229960003943 hypromellose Drugs 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical group [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 5
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 239000001856 Ethyl cellulose Substances 0.000 claims description 4
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 4
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 4
- 229920001249 ethyl cellulose Polymers 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 229920003151 Eudragit® RL polymer Polymers 0.000 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 239000000853 adhesive Substances 0.000 claims description 3
- 230000001070 adhesive effect Effects 0.000 claims description 3
- 238000005469 granulation Methods 0.000 claims description 3
- 230000003179 granulation Effects 0.000 claims description 3
- DNKKLDKIFMDAPT-UHFFFAOYSA-N n,n-dimethylmethanamine;2-methylprop-2-enoic acid Chemical compound CN(C)C.CC(=C)C(O)=O.CC(=C)C(O)=O DNKKLDKIFMDAPT-UHFFFAOYSA-N 0.000 claims description 3
- 239000000049 pigment Substances 0.000 claims description 3
- 238000010298 pulverizing process Methods 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 2
- 239000004925 Acrylic resin Substances 0.000 claims description 2
- 229920000178 Acrylic resin Polymers 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 229920003136 Eudragit® L polymer Polymers 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 2
- 239000008119 colloidal silica Substances 0.000 claims description 2
- 239000003925 fat Substances 0.000 claims description 2
- 235000019197 fats Nutrition 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 229950005770 hyprolose Drugs 0.000 claims description 2
- 239000003921 oil Substances 0.000 claims description 2
- 235000019198 oils Nutrition 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 239000010409 thin film Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 6
- 239000011248 coating agent Substances 0.000 abstract description 5
- 238000000576 coating method Methods 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 28
- 238000002360 preparation method Methods 0.000 description 18
- 239000004359 castor oil Substances 0.000 description 6
- 235000019438 castor oil Nutrition 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 6
- 229920003148 Eudragit® E polymer Polymers 0.000 description 5
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 229920003152 Eudragit® RS polymer Polymers 0.000 description 2
- FSXVSUSRJXIJHB-UHFFFAOYSA-M ethyl prop-2-enoate;methyl 2-methylprop-2-enoate;trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CCOC(=O)C=C.COC(=O)C(C)=C.CC(=C)C(=O)OCC[N+](C)(C)C FSXVSUSRJXIJHB-UHFFFAOYSA-M 0.000 description 2
- 230000010355 oscillation Effects 0.000 description 2
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 241000256844 Apis mellifera Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- -1 fluidizer Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000005184 men's health Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Abstract
The present invention provides a method for preparing controlled release tablets of diltiazem hydrochloride, which comprises the steps: preparing tablet cores; coating a controlled release coating and a quick release coating. The method of the present invention can be used for preparing controlled release tablets of diltiazem hydrochloride, and the tablets need to be taken one time or two times a day and have the weights of more than 200 mg. The present invention can effectively control the release of medicines in a special time, reduce the frequency of medicine administration and raise curative effects.
Description
The invention belongs to pharmaceutical controlled release formulation preparation method technical field.
The medicine diltiazem hydrochloride of cardiovascular disease resistant has been widely used in clinical, treatment vascular hypertension and angina pectoris.The diltiazem hydrochloride slow releasing preparation that the eighties doomsday clothes are 2 times begins listing, and the diltiazem hydrochloride controlled release preparation of obeying 1 day the early 1990s begins listing.USP5,000,962 had once reported the diltiazem hydrochloride controlled release tablet of day clothes 1 time, this patents state first preparation hypromellose matrix core, the controlled release tablet of making through sustained release coating then.But the hypromellose consumption of label is big in this preparation method, tablet weight is big, in addition, does not have release layer in tablet, and discharge wayward early stage.
Purpose of the present invention is intended to improve the preparation technique level, the diltiazem hydrochloride slow-release tablet that preparation day clothes 2 times or day clothes are 1 time.Make it keep effective blood drug concentration in long period in vivo, conveniently take medicine, improve the compliance that patient takes medicine.
The invention provides the preparation method of diltiazem hydrochloride controlled release tablet.
The preparation method of diltiazem hydrochloride controlled release tablet of the present invention comprises the following steps:
(1) diltiazem hydrochloride active ingredient after the pulverizing and water wetted material hydrophobic material, filler, binding agent mixing granulation with fluidizer, lubricant mixing, are pressed into the slow release label again;
(2) on the slow release label, pack the controlled release thin film;
(3) pack the release layer of hydrochloric diltiazem active ingredient at last.
With the diltiazem hydrochloride controlled release tablet of the inventive method preparation by forming as the diltiazem hydrochloride of active ingredient and other pharmaceutical carriers.Pharmaceutical carrier wherein has water wetted material, hydrophobic material, filler, binding agent, fluidizer, lubricant, film clothing material, plasticizer, pigment etc.
Above-mentioned water wetted material can be hyprolose, hypromellose, Carboxymethyl cellulose sodium or sodium alginate; Hydrophobic material can be hydrogenated oil and fat, magnesium stearate or stearic acid; Filler can be calcium hydrogen phosphate, lactose or calcium carbonate; Binding agent can be methylcellulose or polyvinylpyrrolidone; Fluidizer can be colloidal silica or Pulvis Talci; Lubricant can be magnesium stearate, stearic acid or Polyethylene Glycol; Film clothing material can be ethyl cellulose or hypromellose or acrylic resin; Lubricant can be Pulvis Talci, magnesium stearate or stearic acid; Plasticizer can be diethyl phthalate or propylene glycol or Oleum Ricini.
Be used for that the present invention prepares the active ingredient diltiazem hydrochloride of diltiazem hydrochloride controlled release tablet and pharmaceutical carrier is to select to make 100% composition by following proportioning. (1) label composition diltiazem hydrochloride 10-80% water wetted material 5-60% hydrophobic material 5-30% filler 5-40% adhesive 0.5-10% glidant 0.1-5% lubricant 0.1-5% (2) controlled release coat composition film clothing material 1-10% lubricant 0.1-5% plasticizer 0.1-3% (3) quick-release dressing composition diltiazem hydrochloride 1-30% film clothing material 1-10% plasticizer 0.1-2% lubricant 0.1-2% pigment is an amount of
Stability test with the diltiazem hydrochloride controlled release tablet of the inventive method preparation is reported as follows: 1, room temperature storage stability data
Sample packaging: tablet is packed into airtight in the high density ethylene bottle.
The dissolution determination method of diltiazem hydrochloride controlled release tablet: according to dissolution method first method (60 pages of two appendix of Chinese Pharmacopoeia nineteen ninety version), rotating speed is that per minute 100 changes, with water 900ml is solvent, and stripping solution is with the spectrophotometry trap and calculate stripping quantity.
The diltiazem hydrochloride controlled release tablet of the inventive method preparation has been carried out the consubstantiality cross matching with diltiazem hydrochloride ordinary tablet (Chinese Pharmacopoeia nineteen ninety version) in 8 men's health volunteers, the result shows:
During single dose (180mg), the half-life (ty of controlled release tablet and ordinary tablet
2) be respectively 8.09 hours and 4.62 hours, reaching the honeybee time (Tpeak) to be respectively 7.034 hours and 3.224 hours, the index of oscillation (FI) is respectively 0.84 and 0.82, and notable difference is all arranged.The relative bioavailability of controlled release tablet is 0.941.
Effective blood concentration scope of diltiazem hydrochloride it is reported and is 50-200mg/ml, result of the test shows, during stable state, the paddy concentration of controlled release tablet (180mg, day clothes 1 time serve on 5 days) is about 80ng/ml, in effective blood concentration scope, and the stable state paddy concentration 73ng/ml that is higher than ordinary tablet (60mg, day clothes 3 times serve on 3 days); The stable state peak concentration of controlled release tablet is 133ng/ml, is starkly lower than the 176ng/ml of ordinary tablet.
Above presentation of results can be controlled medicine release within a certain period of time effectively by the diltiazem hydrochloride controlled release tablet of the inventive method preparation, obey day can keep for 1 time and reach effective blood concentration of 24 hours, and the index of oscillation is little, absorb good, taking convenience not only, and more help improving curative effect, reduce incidence rate of adverse reaction.
Example one, preparation diltiazem hydrochloride controlled release tablet 1, label are formed
Mg/ sheet diltiazem hydrochloride 85 sodium alginates (water wetted material) 80 rilanit specials (hydrophobic material) 20 lactose (filler) 10 calcium monohydrogen phosphates (filler) 15 methylcellulose (adhesive) 15 colloidal state Silica (glidant) 0.5 dolomols (lubricant) 42, controlled release layer form Eudragit RL (film clothing material) 14 Eudragit L (film clothing material) 1 talcum powder (lubricant), 0.5 castor oil (plasticizer) 0.53, release layer forms diltiazem hydrochloride 5 Hydroxypropyl methylcelluloses (film clothing material) 5 polyethylene glycol (lubricant), 0.4 castor oil (plasticizer) 0.4
Operational approach:
1. by above-mentioned formula ratio diltiazem hydrochloride and solid adjuvant material pulverizing are sieved, and then with filler, binding agent mixing granulation, with lubricant, fluidizer mixing, be pressed into label again;
2. prepare controlled release coat liquid and rapid release coating solution respectively by above-mentioned formula ratio;
3. the label that makes is packed controlled release layer earlier, pack release layer then;
4. with the Film coated tablets drying, the test package that pack.Dissolution: example two, preparation diltiazem hydrochloride controlled release tablet 1, label were formed in 1 hour 4 hours 8 hours 12 hours 16 hours 24 hours 6.2% 22.7% 50.3% 72.6% 87.3% 96.4%
It is identical with example one that mg/ sheet diltiazem hydrochloride 75 sodium carboxymethylcelluloses 60 calcium carbonate 12 dolomols 12 methylcellulose 3 talcum powder 5 colloidal silicas 0.5 stearic acid 32, controlled release layer form ethyl cellulose 8 Eudragit E 3 stearic acid 0.5 diethyl phthalate 0.5 polyethylene glycol 0.53, release layer forms diltiazem hydrochloride 15 Eudragit E 5 castor oil 0.5 dolomol 0.5 method of operating. Dissolution:example three, preparation diltiazem hydrochloride controlled release tablet 1, label were formed in 1 hour 4 hours 8 hours 12 hours 16 hours 24 hours 17.5% 30.2% 50.6% 68.7% 82.9% 95.4%
It is identical with example one that mg/ sheet diltiazem hydrochloride 160 Hydroxypropyl methylcelluloses 30 rilanit specials 30 stearic acid 10 calcium monohydrogen phosphates 15 polyvinylpyrrolidones 3 talcum powder 4 colloidal silicas 1 dolomol 22, controlled release layer form Eudragit RS 11 Eudragit E 1 talcum powder 0.5 diethyl phthalate 0.53, release layer forms diltiazem hydrochloride 20 Hydroxypropyl methylcelluloses 5 talcum powder 0.5 propane diols 0.6 method of operating.
Dissolution:
1 hour 4 hours 8 hours 12 hours 16 hours 24 hours
12.1% 31.3% 56.1% 75.2% 88.5% 96.7% examples four, preparation diltiazem hydrochloride controlled release tablet 1, label are formed
It is identical with example one that mg/ sheet diltiazem hydrochloride 80 L-HPCs 70 rilanit specials 40 calcium monohydrogen phosphates 15 dolomols 20 polyvinylpyrrolidones 1.5 talcum powder 5 colloidal silicas 1 dolomol 22, controlled release layer form ethyl cellulose 6 dolomols 0.3 propane diols 0.5 polyethylene glycol 0.53, release layer forms diltiazem hydrochloride 10 Eudragit E 3.5 polyethylene glycol 0.4 castor oil 0.4 method of operating. Dissolution:example five, preparation diltiazem hydrochloride controlled release tablet 1, label were formed in 1 hour 4 hours 8 hours 12 hours 16 hours 24 hours 11.8% 22.3% 46.7% 65.1% 82.9% 93.8%
It is identical with example one that mg/ sheet diltiazem hydrochloride 80 Hydroxypropyl methylcelluloses 90 rilanit specials 20 lactose 25 calcium carbonate 8 polyvinylpyrrolidones 3 talcum powder 5 colloidal silicas 0.5 dolomol 32, controlled release layer form Eudragit RS 3 Eudragit E 1 Eudragit RL 3 talcum powder 0.5 castor oil 0.53, release layer forms diltiazem hydrochloride 10 Hydroxypropyl methylcelluloses 3 polyethylene glycol 0.4 castor oil 0.4 method of operating. Dissolution:1 hour 4 hours 8 hours 12 hours 15 hours 24 hours 11.5% 29.3% 53.6% 74.1% 86.5% 94.3%
Claims (3)
1, a kind of method for preparing diltiazem hydrochloride controlled release tablet is characterized in that the method comprises the following steps: I, form: an amount of II of (1) label composition diltiazem hydrochloride 10-80% water wetted material 5-60% hydrophobic material 5-30% filler 5-40% adhesive 0.5-10% glidant 0.1-5% lubricant 0.1-5% (2) controlled release coat composition film clothing material 1-10% lubricant 0.1-5% plasticizer 0.1-3% (3) quick-release dressing composition diltiazem hydrochloride 1-30% film clothing material 1-10% plasticizer 0.1-2% lubricant 0.1-2% pigment, method:
(1) diltiazem hydrochloride active ingredient after the pulverizing and water wetted material hydrophobic material, filler, binding agent mixing granulation with fluidizer, lubricant mixing, are pressed into the slow release label again;
(2) on the slow release label, pack the controlled release thin film;
(3) pack the release layer of your active ingredient hydrochloricly at last.
2, the method for preparing diltiazem hydrochloride controlled release tablet according to claim 1 is characterized in that wherein said pharmaceutical carrier water wetted material is hyprolose, hypromellose, Carboxymethyl cellulose sodium or sodium alginate; Hydrophobic material is hydrogenated oil and fat, magnesium stearate or stearic acid; Filler is calcium hydrogen phosphate, lactose or calcium carbonate; Binding agent is methylcellulose or polyvinylpyrrolidone; Fluidizer is colloidal silica or Pulvis Talci; Lubricant is magnesium stearate, stearic acid or Polyethylene Glycol; Film clothing material is ethyl cellulose, hypromellose or acrylic resin; Plasticizer is diethyl phthalate or propylene glycol or Oleum Ricini.
3, the method for preparing diltiazem hydrochloride controlled release tablet according to claim 1 and 2 is characterized in that the film clothing material that uses in the wherein said pharmaceutical carrier controlled release layer composition is Eudragit RL and Eudragit L; The film clothing material of release layer is a hypromellose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 95111600 CN1091600C (en) | 1995-04-18 | 1995-04-18 | Process for preparing controlled-release tablet of diltiazem hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 95111600 CN1091600C (en) | 1995-04-18 | 1995-04-18 | Process for preparing controlled-release tablet of diltiazem hydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1133709A CN1133709A (en) | 1996-10-23 |
| CN1091600C true CN1091600C (en) | 2002-10-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 95111600 Expired - Fee Related CN1091600C (en) | 1995-04-18 | 1995-04-18 | Process for preparing controlled-release tablet of diltiazem hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1091600C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579387A (en) * | 2006-09-26 | 2012-07-18 | 诺瓦提斯公司 | Pharmaceutical compositions comprising an S1P modulator |
| CN105012274A (en) * | 2015-06-27 | 2015-11-04 | 上海信谊万象药业股份有限公司 | Omeprazole micro-tablet capsule preparation and preparation method thereof |
| CN110464710A (en) * | 2019-09-02 | 2019-11-19 | 新华制药（高密）有限公司 | A kind of diltiazem hydrochloride * piece and preparation method thereof |
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|---|---|---|---|---|
| CN1296046C (en) * | 2003-12-23 | 2007-01-24 | 广州市医药工业研究所 | Diltiazem hydrochloride control release capsule and its preparing method |
| CN101234095B (en) * | 2007-02-02 | 2011-06-01 | 上海医药工业研究院 | Timely released preparation and preparation thereof |
| CN108524459A (en) * | 2018-06-15 | 2018-09-14 | 天津田边制药有限公司 | A kind of diltiazem agent and preparation method thereof |
| CN113171351A (en) * | 2021-04-02 | 2021-07-27 | 海南锦瑞制药有限公司 | Diltiazem hydrochloride controlled-release pill and preparation method thereof |
-
1995
- 1995-04-18 CN CN 95111600 patent/CN1091600C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579387A (en) * | 2006-09-26 | 2012-07-18 | 诺瓦提斯公司 | Pharmaceutical compositions comprising an S1P modulator |
| CN105012274A (en) * | 2015-06-27 | 2015-11-04 | 上海信谊万象药业股份有限公司 | Omeprazole micro-tablet capsule preparation and preparation method thereof |
| CN110464710A (en) * | 2019-09-02 | 2019-11-19 | 新华制药（高密）有限公司 | A kind of diltiazem hydrochloride * piece and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1133709A (en) | 1996-10-23 |
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