CN102988325B - Preparation method of manidipine sustained release tablet - Google Patents
Preparation method of manidipine sustained release tablet Download PDFInfo
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- CN102988325B CN102988325B CN201210377523.9A CN201210377523A CN102988325B CN 102988325 B CN102988325 B CN 102988325B CN 201210377523 A CN201210377523 A CN 201210377523A CN 102988325 B CN102988325 B CN 102988325B
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- manidipine
- sustained release
- release tablets
- carrageenan
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- ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 title claims abstract description 66
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- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
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- 239000011248 coating agent Substances 0.000 claims abstract description 26
- 238000000576 coating method Methods 0.000 claims abstract description 26
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims abstract description 22
- 239000003826 tablet Substances 0.000 claims abstract description 17
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
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Images
Abstract
The invention relates to a manidipine sustained release tablet for treating hypertension, belonging to the technical field of a Western medicine preparation. The manidipine sustained release tablet consists of a tablet and a coating, and is characterized in that the tablet comprises the following components according to the total weight percentage of the sustained release tablet: 30-70 parts of manidipine, 10-30 parts of carrageenan, 1-10 parts of a lubrication glidant, 5-15 parts of citric acid and 1-20 parts of a sweetening agent; the coating comprises the following components in 100 parts by total weight of the sustained release tablet: 0.5-3 parts of sodium carboxymethylcellulose, 0.5-5 parts of propylene glycol and 0.5-2 parts of the lubrication glidant. The tablet provided by the invention has the advantages of slow release, small side effects on stomachs and intestines, and no bitter taste.
Description
Technical field
The invention belongs to Western medicine preparation technical field, particularly a kind of manidipine sustained release tablets for the treatment of senile dementia.
Background technology
Manidipine is a kind of lipophilic, third generation bihydropyridine type calcium channel blocker, CA registration number is 89226-75-5, molecular formula is C35H38N4O62HCl, molecular weight is 683.62, vascular smooth muscle is had to high selectivity, therefore can induce significantly peripheral vasodilation, and Cardiac depression effect is very slight.In addition, Manidipine can appreciable impact noradrenaline levels, shows that it can not affect sympathetic nervous system.After this drug administration, effect engenders but lastingly, can only take once every day.Manidipine can be exported and input tremulous pulse by diastole kidney, and kidney is had to certain benefit, and to the effect of kidney and its antihypertensive function uncorrelated.Every day, an oral Manidipine was to light effective and toleration is good to moderate hypertension patient.It should be noted that in a large-scale double blind, the patient of Manidipine group generation ankle edema will significantly be less than amlodipine group.Manidipine is also applicable to the hypertensive patient who has a complication, for example type 2 diabetes mellitus and renal function injury.Manidipine can improve insulin sensitivity and not affect metabolic function.In brief, Manidipine can be used as the line medication use that constitutional gently arrives moderate hypertension.
Manidipine is third generation calcium channel blocker, can suppress L-type and T-type calcium channel on smooth muscle cell, makes peripheral vasodilation, causes blood pressure drops.In calcium, the inhibitory action of stream engenders, is scrubbing still sustainable existence of after date effect.After patient takes medicine, effect can continue 24 hours.In recommended dose, Manidipine does not have the impact of clinical remarkable meaning on heart rate or cardiac electrophysiology parameter.The Manidipine of therapeutic dose also can not affect the level of norepinephrine.Manidipine is useful to hypertensive patient's kidney, has had the patient of renal function injury also can use Manidipine.In the clinical trial of participating in the hyperpietic by merging chronic renal insufficiency of 12 weeks by a definite date, patient significantly improves at (every day 10 or 20 milligrams) creatinine clearance rate after Manidipine treatment, and serum creatinine level significantly reduces.And nifedipine (every day 30 or 60 milligrams) does not have above-mentioned effect.
Oral easy absorption, blood drug level peak time 1～2 hour is 97% with albumen knot rate in blood plasma.T1/2 approximately 5 hours, owing to absorbing rapidly, easily causes hypotension.
In sum, study and develop a kind of slow release, gastrointestinal side-effect is little, without the manidipine sustained release tablets of bitterness, seem particularly urgent.
Summary of the invention
In order to overcome the deficiencies in the prior art, the present invention to adjuvant screening and process optimization, provides a kind of manidipine sustained release tablets by lot of experiments.This tablet slow release, gastrointestinal side-effect are little, and without bitterness, preparation technology is simple.
The object of the present invention is achieved like this:
A preparation method for manidipine sustained release tablets, is comprised of plain sheet and coating, by slow releasing tablet total weight percent, described plain sheet consists of the following composition: Manidipine 30-70 part, carrageenan 10-30 part, lubricated fluidizer 1-10 part, citric acid 5-15 part and sweeting agent 1-20 part; Described coating is 100 parts by slow releasing tablet gross weight and consists of the following composition: sodium carboxymethyl cellulose 0.5-3 part, propylene glycol 0.5-5 part, lubricated fluidizer 0.5-2 part.
Above-mentioned a kind of manidipine sustained release tablets, lubricated fluidizer is selected from one or more in magnesium stearate, silicon dioxide, Pulvis Talci.
Above-mentioned a kind of manidipine sustained release tablets, sweeting agent is selected from one or more in lactose, sucrose, glucose, xylitol, sorbitol, mannitol, steviosin, saccharin sodium, aspartame.
Above-mentioned a kind of manidipine sustained release tablets, the plain slice prescription of manidipine sustained release tablets is as follows: Manidipine 500mg, carrageenan 200mg, magnesium stearate 50mg, citric acid 100mg, lactose 200mg; The coated formula of manidipine sustained release tablets is as follows: sodium carboxymethyl cellulose 10.5mg, propylene glycol 20mg, Pulvis Talci 9.5mg.
Above-mentioned a kind of manidipine sustained release tablets, the plain slice prescription of manidipine sustained release tablets is as follows: Manidipine 500mg, carrageenan 300mg, magnesium stearate 20mg, citric acid 50mg, lactose 100mg; The coated formula of manidipine sustained release tablets is as follows: sodium carboxymethyl cellulose 9.5mg, propylene glycol 19mg, Pulvis Talci 15mg.
The preparation method of above-mentioned a kind of manidipine sustained release tablets, the method comprises the following steps: that (1) is dissolved in part carrageenan in alcoholic solution, is prepared into alcoholic solution; (2) Manidipine after sieving, remaining carrageenan, citric acid, sweeting agent are placed in to high efficient mixed comminutor and fully mix, add the alcoholic solution of above-mentioned carrageenan, fully mix, make soft material; (3) after above-mentioned soft material is dry, add lubricated fluidizer, obtain mixed powder, mixed powder all adds Mixers with Multi-direction Movement, uses swinging lozenge machine tabletting, makes plain sheet; (4) preparation of coating solution: will lubricate after fluidizer sieves and mix, and add in the alcoholic solution containing sodium carboxymethyl cellulose and propylene glycol, and use again colloid mill circular grinding after stirring by hand, and make coating solution; (5) plain sheet is joined in atresia coating pan, regulate intake, after plain sheet preheating, add above-mentioned coating solution to carry out coating; (6) by the slow releasing tablet packing making.
Compared with prior art, the manidipine sustained release tablets the present invention relates to has following useful technique effect:
(1) discharge steadily.Limit is within 1 hour, to discharge 25-45%, within 4 hours, discharges 60-85%, within 8 hours, discharges more than 80%.
(2) gastrointestinal side-effect is little, without bitterness, and carrageenan parcel Manidipine raw material for the present invention, the method can be covered Manidipine bitterness and reach beyond thought effect.
(3) preparation technology is simple.The manidipine sustained release tablets of the present invention's screening is applicable to industrialized great production.
Accompanying drawing explanation
Fig. 1 is the In Vitro Dissolution curve of the tablet prepared of embodiment 1 and Manidipine direct compression
The specific embodiment
Form is described in further detail foregoing of the present invention again by the following examples, but this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following example, all technology realizing based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1
The plain slice prescription that takes manidipine sustained release tablets is as follows: Manidipine 500mg, carrageenan 200mg, magnesium stearate 50mg, citric acid 100mg, lactose 200mg; The coated formula of manidipine sustained release tablets is as follows: sodium carboxymethyl cellulose 10.5mg, propylene glycol 20mg, Pulvis Talci 9.5mg.
Preparation technology:
(1) 100mg carrageenan is dissolved in alcoholic solution, is prepared into alcoholic solution; (2) Manidipine after sieving, remaining carrageenan, citric acid, lactose are placed in to high efficient mixed comminutor and fully mix, add the alcoholic solution of above-mentioned carrageenan, fully mix, make soft material; (3) after above-mentioned soft material is dry, add lubricated fluidizer, obtain mixed powder, mixed powder all adds Mixers with Multi-direction Movement, uses swinging lozenge machine tabletting, makes plain sheet; (4) preparation of coating solution: mix after Pulvis Talci is sieved, add in the alcoholic solution containing sodium carboxymethyl cellulose and propylene glycol, use again colloid mill circular grinding after stirring by hand, make coating solution; (5) plain sheet is joined in atresia coating pan, regulate intake, after plain sheet preheating, add above-mentioned coating solution to carry out coating; (6) by the slow releasing tablet packing making.
The plain slice prescription that takes manidipine sustained release tablets is as follows: Manidipine 500mg, carrageenan 300mg, magnesium stearate 20mg, citric acid 50mg, lactose 100mg; The coated formula of manidipine sustained release tablets is as follows: sodium carboxymethyl cellulose 9.5mg, propylene glycol 19mg, Pulvis Talci 15mg.
Preparation technology:
(1) 100mg carrageenan is dissolved in alcoholic solution, is prepared into alcoholic solution; (2) Manidipine after sieving, remaining carrageenan, citric acid, lactose are placed in to high efficient mixed comminutor and fully mix, add the alcoholic solution of above-mentioned carrageenan, fully mix, make soft material; (3) after above-mentioned soft material is dry, add lubricated fluidizer, obtain mixed powder, mixed powder all adds Mixers with Multi-direction Movement, uses swinging lozenge machine tabletting, makes plain sheet; (4) preparation of coating solution: mix after Pulvis Talci is sieved, add in the alcoholic solution containing sodium carboxymethyl cellulose and propylene glycol, use again colloid mill circular grinding after stirring by hand, make coating solution; (5) plain sheet is joined in atresia coating pan, regulate intake, after plain sheet preheating, add above-mentioned coating solution to carry out coating; (6) by the slow releasing tablet packing making.
The release research of embodiment 3 manidipine sustained release tablets
Tablet (seeing comparative example 1 in Fig. 1) prepared by the tablet (specification 50mg) of the embodiment of the present invention 1 preparation and Manidipine direct compression contrasts.
Dissolution test method: get respectively the tablet (specification 50mg) of embodiment 1 preparation and tablet (specification 50mg) prepared by Manidipine direct compression, according to drug release determination method (two appendix X D first methods of Chinese Pharmacopoeia version in 2010), take distilled water 900ml as solvent, Revolution Per Minute 50 turns, operation in accordance with the law, through 1, 4, 8 hours, get solution 10ml, through 0.8um filter membrane, filter immediately, and supplement in time 10ml solvent, it is appropriate that precision measures subsequent filtrate, with distilled water, be quantitatively diluted to the solution that approximately contains 16ug in every 1ml, according to spectrophotography (two appendix VIA of Chinese Pharmacopoeia version in 2000), wavelength place at 252nm measures trap.It is appropriate that another precision takes Manidipine reference substance, with distilled water, dissolves and be also quantitatively diluted to the solution that contains 15 μ g in every 1ml.Be measured in the same method trap, calculate the stripping quantity of every.Limit is within 1 hour, to discharge 25-45%, within 4 hours, discharges 60-85%, within 8 hours, discharges more than 80%.
Claims (5)
1. a manidipine sustained release tablets, is comprised of plain sheet and coating, it is characterized in that by slow releasing tablet gross weight be 100 parts, described plain sheet consists of the following composition: Manidipine 30-70 part, carrageenan 10-30 part, lubricated fluidizer 1-10 part, citric acid 5-15 part and sweeting agent 1-20 part; Described coating is 100 parts by slow releasing tablet gross weight and consists of the following composition: sodium carboxymethyl cellulose 0.5-3 part, propylene glycol 0.5-5 part, lubricated fluidizer 0.5-2 part, preparation process is as follows: (1) is dissolved in part carrageenan in alcoholic solution, is prepared into alcoholic solution; (2) Manidipine after sieving, remaining carrageenan, citric acid, sweeting agent are placed in to high efficient mixed comminutor and fully mix, add the alcoholic solution of above-mentioned carrageenan, fully mix, make soft material; (3) after above-mentioned soft material is dry, add lubricated fluidizer, obtain mixed powder, mixed powder all adds Mixers with Multi-direction Movement, uses swinging lozenge machine tabletting, makes plain sheet; (4) preparation of coating solution: will lubricate after fluidizer sieves and mix, and add in the alcoholic solution containing sodium carboxymethyl cellulose and propylene glycol, and use again colloid mill circular grinding after stirring by hand, and make coating solution; (5) plain sheet is joined in atresia coating pan, regulate intake, after plain sheet preheating, add above-mentioned coating solution to carry out coating; (6) by the slow releasing tablet packing making.
2. a kind of manidipine sustained release tablets as claimed in claim 1, is characterized in that lubricated fluidizer is selected from one or more in magnesium stearate, silicon dioxide, Pulvis Talci.
3. a kind of manidipine sustained release tablets as claimed in claim 1, is characterized in that sweeting agent is selected from one or more in lactose, sucrose, glucose, xylitol, sorbitol, mannitol, steviosin, saccharin sodium, aspartame.
4. a kind of manidipine sustained release tablets as claimed in claim 1, is characterized in that the plain slice prescription of manidipine sustained release tablets is as follows: Manidipine 500mg, carrageenan 200mg, magnesium stearate 50mg, citric acid 100mg, lactose 200mg; The coated formula of manidipine sustained release tablets is as follows: sodium carboxymethyl cellulose 10.5mg, propylene glycol 20mg, Pulvis Talci 9.5mg.
5. a kind of manidipine sustained release tablets as claimed in claim 1, is characterized in that the plain slice prescription of manidipine sustained release tablets is as follows: Manidipine 500mg, carrageenan 300mg, magnesium stearate 20mg, citric acid 50mg, lactose 100mg; The coated formula of manidipine sustained release tablets is as follows: sodium carboxymethyl cellulose 9.5mg, propylene glycol 19mg, Pulvis Talci 15mg.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210377523.9A CN102988325B (en) | 2012-10-08 | 2012-10-08 | Preparation method of manidipine sustained release tablet |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210377523.9A CN102988325B (en) | 2012-10-08 | 2012-10-08 | Preparation method of manidipine sustained release tablet |
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| CN102988325B true CN102988325B (en) | 2014-04-02 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101468009A (en) * | 2007-12-29 | 2009-07-01 | 北京琥珀光华医药科技开发有限公司 | Method for preparing manidipine sustained release tablets and use thereof |
| CN101744760A (en) * | 2008-12-18 | 2010-06-23 | 梁颖 | Sustained release carrier for difficult soluble or easy decomposable drug |
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- 2012-10-08 CN CN201210377523.9A patent/CN102988325B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101468009A (en) * | 2007-12-29 | 2009-07-01 | 北京琥珀光华医药科技开发有限公司 | Method for preparing manidipine sustained release tablets and use thereof |
| CN101744760A (en) * | 2008-12-18 | 2010-06-23 | 梁颖 | Sustained release carrier for difficult soluble or easy decomposable drug |
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| CN102988325A (en) | 2013-03-27 |
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