CN103655561A - Pharmaceutical composition containing losartan potassium and amlodipine besylate and preparation method thereof - Google Patents
Pharmaceutical composition containing losartan potassium and amlodipine besylate and preparation method thereof Download PDFInfo
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- CN103655561A CN103655561A CN201210323471.7A CN201210323471A CN103655561A CN 103655561 A CN103655561 A CN 103655561A CN 201210323471 A CN201210323471 A CN 201210323471A CN 103655561 A CN103655561 A CN 103655561A
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- pharmaceutical composition
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- losartan potassium
- amlodipine besylate
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Abstract
The invention belongs to the field of medical technology and discloses a pharmaceutical composition containing losartan potassium and amlodipine besylate and a preparation method thereof. The pharmaceutical composition is composed of the following components in parts by weight: 50 parts of losartan potassium, 5 parts of amlodipine besylate (based on the weight of amlodipine), 150-250 parts of microcrystalline cellulose, 20-40 parts of polyvinylpolypyrrolidone, 1-5 parts of fumed silica, 1-5 parts of magnesium stearate and 8-16 parts of OPADYR II; the pharmaceutical composition is prepared from powder by a direct tabletting process. The pharmaceutical composition disclosed by the invention is stable in property, simple in production process and capable of being quickly dissolved under a low pH condition.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of pharmaceutical composition that contains Losartan Potassium and Amlodipine Besylate Tablet and preparation method thereof.
Background technology
Hypertension is to cause heart disease, cerebrovascular, nephropathy to occur and dead topmost risk factor, the object of hyperpietic being implemented to antihypertensive drug therapy is, by reducing blood pressure, effectively prevent or postpone the generation of the cardiovascular and cerebrovascular complications such as apoplexy, myocardial infarction, heart failure, renal insufficiency, effectively control hypertensive disease process, the severe hypertensions such as prophylaxis of hypertension emergency case, sub-emergency case occur.
Conventional antihypertensive drugs comprises calcium channel blocker (CCB), angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), diuretic and beta-blocker five classes, and the fixed mixing ratio compound preparation being comprised of said medicine.
AngiotensinⅡ is the active substance of renin-angiotensin system, for potent vasoconstrictor, in hypertensive pathophysiological process, play a major role, losartan belongs to ARB, in vitro study shows, losartan and the carboxylic acid metabolite (E3174) with pharmacologically active thereof can be blocked the physiological action that any source or the synthetic angiotensinⅡ of any approach produce.
Amlodipine belongs to CCB, and it can optionally suppress calcium ion cross-film intravasation smooth muscle and cardiac muscle.Amlodipine is a peripheral arterial vasodilation, and it directly acts on vascular smooth muscle, thereby reduces peripheral vascular resistance and blood pressure.
Losartan Potassium and Amlodipine Besylate Tablet are combined use, and Hypotensive Mechanism is complementary, has the antihypertensive effect of addition, and can cancel out each other or alleviate untoward reaction.
Yet due to following problem, preparation faces the challenge containing the pharmaceutical composition of Losartan Potassium and Amlodipine Besylate Tablet:
First problem is the stability of Losartan Potassium.When Losartan Potassium heats under acid condition, poor stability is (referring to Z.Zhao, Q.Wang, E.W.Tsai, X.-Z.Quin and D.Ip, J.Pharm.Biomed.Anal.20,129-136,1999), preparation is containing the pharmaceutical composition of Losartan Potassium and Amlodipine Besylate Tablet, adopts conventional wet granulation technology or poor than the single preparations of ephedrine storage stability of Losartan Potassium and Amlodipine Besylate Tablet by the combination preparation that Losartan Potassium and Amlodipine Besylate Tablet are simply mixed with.
Second Problem is the gelation of Losartan Potassium.Losartan purified water or under relatively high pH condition (for example pH6.8) can well discharge; but (for example pH2.0) its meeting make to discharge very slow because of gelation under low pH condition; while is due to the gelation of Losartan Potassium; amlodipine is wrapped in gel; it is also difficult to stripping under low pH condition, affects the absorption of medicine.
For the problems referred to above, publication number is the compositions that the Chinese patent of CN101472587A discloses a kind of amlodipine or the acceptable salt of its materia medica and losartan or the acceptable salt of its materia medica, amlodipine or the acceptable salt of its materia medica and losartan or the acceptable salt of its materia medica physics separated each other in said composition; Publication number is that the Chinese patent of CN102292070A discloses a kind of pharmaceutical composition, the amlodipine that comprises separated particle form and losartan, and stabilizing agent; Publication number is that the Chinese patent of CN102292085A discloses a kind of solid composite medicament, comprises separated amlodipine or the acceptable salt of its pharmacy and losartan or the acceptable salt of its pharmacy.
Above-mentioned patent all adopts amlodipine or the acceptable salt of its materia medica and losartan or the separated mode pharmaceutical compositions of the acceptable salt of its materia medica, and preparation method comprises: compacting double-layer tablet, by one deck amlodipine or the acceptable salt coating of its materia medica for the tablet of losartan or its pharmacological-acceptable salt, by Amlodipine Besylate Tablet and Losartan Potassium, granulate respectively etc.In above-mentioned preparation method, compacting double-layer tablet needs special bilayer tablet tablet machine, higher to equipment requirements, easily occurs mass deviation in tabletting process, and reduces because tabletting Speed Reduction makes productivity ratio; By one deck amlodipine or the acceptable salt coating of its materia medica and the equal more complicated of preparation method that Amlodipine Besylate Tablet and Losartan Potassium are granulated respectively for the tablet of losartan or its pharmacological-acceptable salt, production efficiency is low.
In addition, publication number is that the Chinese patent of CN102292084A also discloses a kind of solid composite medicament, and it comprises as the amlodipine of active component and losartan and the disintegrating agent of mixture that is selected from least two kinds of components of sodium starch glycollate, cross-linking sodium carboxymethyl cellulose and polyvinylpolypyrrolidone.We study discovery, in this patent, used disintegrating agent sodium starch glycollate, we know, part hyperpietic also takes vitamin C and carries out auxiliary treatment when taking antihypertensive drug, because sodium starch glycollate and vitamin C have incompatibility, take simultaneously and may produce adverse influence with vitamin C.
For above-mentioned defect, special proposition the present invention.
Summary of the invention
The object of the present invention is to provide a kind of stable in properties, production technology is simple, can the Losartan Potassium of Fast Stripping and the pharmaceutical composition of Amlodipine Besylate Tablet under low pH condition.
The inventor finds after a large amount of research having carried out, and the preparation method of the stability of the pharmaceutical composition of Losartan Potassium and Amlodipine Besylate Tablet and the supplementary product kind of use and employing is closely related.By carrying out the compatibility test of supplementary material, filter out microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate etc. and can stablize with Losartan Potassium, Amlodipine Besylate Tablet the adjuvant coexisting.Get Losartan Potassium, Amlodipine Besylate Tablet and above-mentioned adjuvant, Losartan Potassium prepared by employing technique of direct powder compression and the pharmaceutical composition of Amlodipine Besylate Tablet have good stability through investigating.The inventor is also unexpected discovery under study for action, when the amount of controlling the adjuvants such as microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate is within the scope of certain proportion, the pharmaceutical composition (for example pH2.0) under low pH condition of preparation can collapse rapidly loose, and Losartan Potassium and Amlodipine Besylate Tablet all can Fast Strippings.The present invention completes based on above discovery.
The invention provides a kind of pharmaceutical composition that contains Losartan Potassium and Amlodipine Besylate Tablet, the formula of this pharmaceutical composition is composed as follows:
Preferably, the formula of this pharmaceutical composition is composed as follows:
The present invention also provides a kind of preparation method of the pharmaceutical composition that contains Losartan Potassium and Amlodipine Besylate Tablet, and this preparation method comprises the steps:
(1) Amlodipine Besylate Tablet is pulverized, sieved, Losartan Potassium is sieved, standby;
(2) microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate are sieved respectively, standby;
(3) take Losartan Potassium, Amlodipine Besylate Tablet, microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and the magnesium stearate of recipe quantity, mix;
(4) mixed material step (3) being obtained sieves;
(5) material after step (4) is sieved mixes;
(6) mixed material tabletting step (5) being obtained;
(7) take recipe quantity
iI, is dispersed in appropriate purified water, is mixed with coating solution;
(8) tablet step (6) being obtained is put in coating pan, with coating solution, carries out coating.
According to aforesaid preparation method, wherein, sieving as crossing 80～120 mesh sieves described in step (1).
According to aforesaid preparation method, wherein, sieving as crossing 40～60 mesh sieves described in step (2).
According to aforesaid preparation method, wherein, sieving as crossing 40～60 mesh sieves described in step (4).
The specific embodiment
The following specific embodiment is that the present invention is not limited only to following examples to further elaboration of the present invention.
Embodiment 1: the preparation of Losartan Potassium amlodipine
1. write out a prescription
2. preparation method
(1) Losartan Potassium and Amlodipine Besylate Tablet are pulverized respectively to rear mistake 80 mesh sieves, standby;
(2) microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate are crossed respectively to 60 mesh sieves, standby;
(3) take Losartan Potassium, Amlodipine Besylate Tablet, microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and the magnesium stearate of recipe quantity, mix;
(4) mixed material step (3) being obtained is crossed 40 mesh sieves;
(5) material after step (4) is sieved mixes;
(6) mixed material tabletting step (5) being obtained;
(7) take recipe quantity
iI, is dispersed in appropriate purified water, is mixed with coating solution;
(8) tablet step (6) being obtained is put in coating pan, with coating solution, carries out coating.
Embodiment 2: the preparation of Losartan Potassium amlodipine
1. write out a prescription
2. preparation method
(1) Losartan Potassium and Amlodipine Besylate Tablet are pulverized respectively to rear mistake 120 mesh sieves, standby;
(2) microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate are crossed respectively to 60 mesh sieves, standby;
(3) take Losartan Potassium, Amlodipine Besylate Tablet, microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and the magnesium stearate of recipe quantity, mix;
(4) mixed material step (3) being obtained is crossed 60 mesh sieves;
(5) material after step (4) is sieved mixes;
(6) mixed material tabletting step (5) being obtained;
(7) take recipe quantity
iI, is dispersed in appropriate purified water, is mixed with coating solution;
(8) tablet step (6) being obtained is put in coating pan, with coating solution, carries out coating.
Embodiment 3: the preparation of Losartan Potassium amlodipine
1. write out a prescription
2. preparation method
(1) Losartan Potassium and Amlodipine Besylate Tablet are pulverized respectively to rear mistake 100 mesh sieves, standby;
(2) microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate are crossed respectively to 50 mesh sieves, standby;
(3) take Losartan Potassium, Amlodipine Besylate Tablet, microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and the magnesium stearate of recipe quantity, mix;
(4) mixed material step (3) being obtained is crossed 50 mesh sieves;
(5) material after step (4) is sieved mixes;
(6) mixed material tabletting step (5) being obtained;
(7) take recipe quantity
iI, is dispersed in appropriate purified water, is mixed with coating solution;
(8) tablet step (6) being obtained is put in coating pan, with coating solution, carries out coating.
Embodiment 4: the preparation of Losartan Potassium amlodipine
1. write out a prescription
2. preparation method
(1) Losartan Potassium and Amlodipine Besylate Tablet are pulverized respectively to rear mistake 80 mesh sieves, standby;
(2) microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate are crossed respectively to 50 mesh sieves, standby;
(3) take Losartan Potassium, Amlodipine Besylate Tablet, microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and the magnesium stearate of recipe quantity, mix;
(4) mixed material step (3) being obtained is crossed 40 mesh sieves;
(5) material after step (4) is sieved mixes;
(6) mixed material tabletting step (5) being obtained;
(7) take recipe quantity
iI, is dispersed in appropriate purified water, is mixed with coating solution;
(8) tablet step (6) being obtained is put in coating pan, with coating solution, carries out coating.
Embodiment 5: the preparation of Losartan Potassium amlodipine
1. write out a prescription
2. preparation method
(1) Losartan Potassium and Amlodipine Besylate Tablet are pulverized respectively to rear mistake 100 mesh sieves, standby;
(2) microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate are crossed respectively to 60 mesh sieves, standby;
(3) take Losartan Potassium, Amlodipine Besylate Tablet, microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and the magnesium stearate of recipe quantity, mix;
(4) mixed material step (3) being obtained is crossed 50 mesh sieves;
(5) material after step (4) is sieved mixes;
(6) mixed material tabletting step (5) being obtained;
(7) take recipe quantity
iI, is dispersed in appropriate purified water, is mixed with coating solution;
(8) tablet step (6) being obtained is put in coating pan, with coating solution, carries out coating.
Embodiment 6: dissolution determination
Get the tablet of embodiment 1～5, carry out Dissolution Rate Testing.
[experimental condition]
Dissolution Rate Testing method: slurry method (ChP.2010), 50 revs/min
Dissolution medium: 0.01mol/L hydrochloric acid solution (pH2.0) 900ml
Temperature: 37 ℃
Sample time: 30 minutes
[analytical method]
Chromatographic column: ODS post (5 μ m, 4.6 * 150mm)
Mobile phase: 10mmol/L sodium dihydrogen phosphate (with phosphorus acid for adjusting pH value to 3.0) acetonitrile (1: 1)
Detector: ultraviolet spectrophotometer (250nm)
Flow velocity: 1.0ml/ minute
Sampling volume: 20p μ l
[measurement result]
Dissolution determination the results are shown in Table 1.
Table 1 dissolution determination result
From the measurement result of table 1, the tablet of embodiment 1～5 in 0.01mol/L hydrochloric acid solution (pH2.0) 30 minutes time the stripping quantity of Losartan Potassium and Amlodipine Besylate Tablet all more than 90%.
Embodiment 7: stability test
1. accelerated test
Get the tablet of embodiment 1, adopt aluminium-plastic bubble plate packing, under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%, place 6 months, in 1st month, 2 months, 3 months, 6 samplings at the end of month of duration of test, the character of sample for reference, related substance, dissolution and content, and compare with the result of 0 month.Separately get commercially available Losartan Tablet (losartan
with commercially available amlodipine besylate tablets (Norvasc
with method, test.Accelerated test the results are shown in Table 2.
Table 2 accelerated test result
Result by table 2 can learn, the every check result of the tablet of embodiment 1 and relatively having no significant change for 0 month under accelerated test, and its stability is not less than commercially available single preparations of ephedrine, has good stability.
2. long term test
Get the tablet of embodiment 1, adopt aluminium-plastic bubble plate packing, under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%, place 6 months, in duration of test 3rd month and 6 samplings at the end of month, the character of sample for reference, related substance, dissolution and content, and compare with the result of 0 month.Separately get commercially available Losartan Tablet (losartan
with commercially available amlodipine besylate tablets (Norvasc
with method, test.Long-term test results is in Table 3.
Table 3 long-term test results
Result by table 3 can learn, the every check result of the tablet of embodiment 1 and relatively having no significant change for 0 month under long term test, and its stability is not less than commercially available single preparations of ephedrine, has good stability.
Claims (6)
1. a pharmaceutical composition that contains Losartan Potassium and Amlodipine Besylate Tablet, is characterized in that, the formula of described pharmaceutical composition is composed as follows:
2. pharmaceutical composition according to claim 1, is characterized in that, the formula of described pharmaceutical composition is composed as follows:
3. the preparation method of pharmaceutical composition according to claim 1 and 2, is characterized in that, described preparation method comprises the steps:
(1) by Losartan Potassium and Amlodipine Besylate Tablet difference grinding and sieving, standby;
(2) microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate are sieved respectively, standby;
(3) take Losartan Potassium, Amlodipine Besylate Tablet, microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel and the magnesium stearate of recipe quantity, mix;
(4) mixed material step (3) being obtained sieves;
(5) material after step (4) is sieved mixes;
(6) mixed material tabletting step (5) being obtained;
(7) take recipe quantity
iI, is dispersed in appropriate purified water, is mixed with coating solution;
(8) tablet step (6) being obtained is put in coating pan, with coating solution, carries out coating.
4. preparation method according to claim 3, is characterized in that, sieving as crossing 80～120 mesh sieves described in step (1).
5. preparation method according to claim 3, is characterized in that, sieving as crossing 40～60 mesh sieves described in step (2).
6. preparation method according to claim 3, is characterized in that, sieving as crossing 40～60 mesh sieves described in step (3).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210323471.7A CN103655561A (en) | 2012-08-28 | 2012-08-28 | Pharmaceutical composition containing losartan potassium and amlodipine besylate and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210323471.7A CN103655561A (en) | 2012-08-28 | 2012-08-28 | Pharmaceutical composition containing losartan potassium and amlodipine besylate and preparation method thereof |
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|---|---|
| CN103655561A true CN103655561A (en) | 2014-03-26 |
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|---|---|---|---|
| CN201210323471.7A Pending CN103655561A (en) | 2012-08-28 | 2012-08-28 | Pharmaceutical composition containing losartan potassium and amlodipine besylate and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110215455A (en) * | 2019-03-26 | 2019-09-10 | 山东省药学科学院 | A kind of pharmaceutical formulation for blood pressure lowering |
| CN112274490A (en) * | 2020-11-19 | 2021-01-29 | 四川尚锐生物医药有限公司 | Preparation method of amlodipine and losartan potassium compound composition |
-
2012
- 2012-08-28 CN CN201210323471.7A patent/CN103655561A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110215455A (en) * | 2019-03-26 | 2019-09-10 | 山东省药学科学院 | A kind of pharmaceutical formulation for blood pressure lowering |
| CN112274490A (en) * | 2020-11-19 | 2021-01-29 | 四川尚锐生物医药有限公司 | Preparation method of amlodipine and losartan potassium compound composition |
| CN112274490B (en) * | 2020-11-19 | 2022-11-22 | 四川尚锐生物医药有限公司 | Preparation method of amlodipine and losartan potassium compound composition |
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Application publication date: 20140326 |