CN1091600C - Process for preparing controlled-release tablet of diltiazem hydrochloride - Google Patents
Process for preparing controlled-release tablet of diltiazem hydrochloride Download PDFInfo
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- 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
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- diltiazem hydrochloride
- controlled release
- lubricant
- release tablet
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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 |
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| Country | Link |
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| 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 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 | A kind of time-release preparation and preparation method 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 |
| CN120554314A (en) * | 2025-01-14 | 2025-08-29 | 北京远大九和药业有限公司 | Crystal form of compound, preparation method thereof, raw material drug, composition and use 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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Granted publication date: 20021002 Termination date: 20140418 |