CN105395509A - Preparation method for losartan potassium tablet - Google Patents
Preparation method for losartan potassium tablet Download PDFInfo
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- CN105395509A CN105395509A CN201510945518.7A CN201510945518A CN105395509A CN 105395509 A CN105395509 A CN 105395509A CN 201510945518 A CN201510945518 A CN 201510945518A CN 105395509 A CN105395509 A CN 105395509A
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- losartan
- losartan potassium
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- tablet
- potassium
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method for a losartan potassium tablet. The method employs a powder direct pressing technology for preparing the losartan potassium tablet, does not have special requirements on equipment, is simple and safe in whole preparation process, and is convenient for industrial production. Water or ethanol is not used as a solvent in the preparation process, and high-temperature drying is not needed in the subsequent process, influence of a high-humidity high-temperature environment on the main drug losartan potassium is avoided, also losartan potassium is prevented from permeating to the particle surface along with evaporation of water or ethanol during drying, the difference among samples is effectively reduced, and the medicine stability is improved. Additionally, selection of appropriate particle size of losartan potassium is the key point for successfully preparing the losartan potassium tablet. The particle size of losartan potassium is set in the following scope: 54 mu m<=d(0.5)<=107 mu m, and 125 mu m<=d(0.9)<=278 mu m, on the one hand, losartan potassium can be uniformly mixed with auxiliary materials, and on the other hand, the medicine individual difference is relatively small, the integrity stability is good, and losartan potassium is prone to dissolve out.
Description
Technical field
The present invention relates to the preparing technical field of pharmaceutical preparation, specifically refer to a kind of preparation method of Losartan Tablet.
Background technology
Losartan Potassium is a kind of in angiotensin ii receptor antagonist, and it can optionally in conjunction with AT1 receptor, produces and comprises the biological effect that vasoconstriction and aldosterone are released in interior plurality of Chinese.Its times is used for the treatment of essential hypertension, and can use together with other antihypertensive drug.
At present, the preparation method of Losartan Potassium preparation is mainly wet granulation.Such as, application publication number is Chinese invention patent application " a kind of losartan potassium capsules and production technology thereof the " (application number: 201510355248.4) disclose a kind of wet granulation method of CN104971055A, its step comprises the process of raw material, mixing, granulation, filling, aluminum-plastic packaged, outer package successively, dehydrated alcohol is mainly used to carry out wet granulation as binding agent, the requirement of explosion proof of said method to production equipment is higher, and there is certain production safety hidden danger.Application publication number is Chinese invention patent application " a kind of pharmaceutical composition containing Losartan Potassium and preparation method thereof the " (application number: a kind of method 201110250254.5) also disclosing wet granulation of CN102335149A, its main preparation process is, first prepare blank granules, then by principal agent Losartan Potassium and magnesium stearate lubricant additional, in order to make magnesium stearate and principal agent Losartan Potassium mix homogeneously with other component in the method, have employed the mixed method that equivalent is progressively increased, although the method reaches the object of mix homogeneously, but because the mixed process time is longer, not only have impact on preparation efficiency, also very easily cause magnesium stearate mixed transition and affect the stripping of Losartan Potassium, and then affect drug effect.In addition, Losartan Potassium is soluble in water with in ethanol, when wet granulation with water makes wetting agent, the viscosity of Losartan Potassium can be brought out, easily make material agglomerating, after dry, granule is comparatively hard, affects the stripping of Losartan Potassium, and easily infiltrate into particle surface along with the evaporation Losartan Potassium of water or ethanol, cause there is larger difference between same batch sample.Meanwhile, adopt wet granulation method, hot and humid environment very easily affects the stability of medicine.
Therefore, for the preparation method of Losartan Tablet in prior art, await doing further improvement.
Summary of the invention
Technical problem to be solved by this invention is the present situation for prior art, provides that a kind of preparation method is simple and safe, difference is little between medicine, stability is high and principal agent is easy to the preparation method of the Losartan Tablet of stripping.
The present invention solves the problems of the technologies described above adopted technical scheme: a kind of preparation method of Losartan Tablet, it is characterized in that comprising the following steps:
(1) each component proportion is designed: the component of described Losartan Tablet and content are
(2) by mix homogeneously after Losartan Potassium, filler, disintegrating agent and binding agent respectively mistake 40 ~ 60 mesh sieves;
(3) add in step (2) gained mixture after lubricant being crossed 40 ~ 50 mesh sieves, tabletting after mix homogeneously, and coating;
The particle diameter of above-mentioned Losartan Potassium is 54 μm≤d (0.5)≤107 μm, 125 μm≤d (0.9)≤278 μm.
As improvement, the particle diameter of described Losartan Potassium is 10 μm≤d (0.1)≤24 μm, 54 μm≤d (0.5)≤100 μm, 130 μm≤d (0.9)≤270 μm.10 μm≤d (0.1)≤24 μm represent in Losartan Potassium have the Losartan Potassium particle diameter of 10% mass parts below 10 ~ 24 μm, accordingly, 54 μm≤d (0.5)≤100 μm represent in Losartan Potassium have the Losartan Potassium particle diameter of 50% mass parts below 54 ~ 100 μm, and 130 μm≤d (0.9)≤270 μm represent in Losartan Potassium have the Losartan Potassium particle diameter of 90% mass parts below 130 ~ 270 μm.
Improve, the particle diameter of described Losartan Potassium is 10 μm≤d (0.1)≤19 μm, 54 μm≤d (0.5)≤87 μm, 135 μm≤d (0.9)≤234 μm again.
As preferably, described filler is one or more in starch, lactose, mannitol.
Preferably, described disintegrating agent is one or more in microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, carboxymethylstach sodium.
Preferably, described binding agent is one or more in pregelatinized Starch, hypromellose, hydroxypropyl cellulose.
Preferably, described lubricant is one or more in magnesium stearate, stearic acid, sodium stearyl fumarate.
Preferably, the component of described Losartan Tablet and content are
Preferably, the component of described Losartan Tablet and content are
Compared with prior art, the invention has the advantages that: the present invention adopts powder vertical compression technique to prepare Losartan Tablet, preparation method is to equipment without particular/special requirement, and whole preparation process is simple and safe, is convenient to realize suitability for industrialized production, without the need to using water or ethanol etc. as solvent in preparation process of the present invention, subsequent process is also without the need to carrying out hyperthermia drying, avoid the impact of high humidity hot environment on principal agent Losartan Potassium, it also avoid Losartan Potassium and infiltrate into particle surface with moisture or ethanol evaporation in dry run, effectively reduce sample room difference, improve the stability of medicine, in addition, suitable Losartan Potassium particle diameter is selected to be the key that the present invention successfully prepares Losartan Tablet, particle diameter too conference causes mixing between Losartan Potassium with adjuvant uneven, produce layering even in process of production, the too little meeting of particle diameter makes the mobility of material and compressibility be deteriorated, cause sheet heavy unstable, glutinous punching, puckery punching, the phenomenons such as sliver, the particle diameter of Losartan Potassium is set as 54 μm≤d (0.5)≤107 μm by the present invention, 125 μm≤d (0.9)≤278 μm, Losartan Potassium is made to be able to mix homogeneously with adjuvant on the one hand, on the other hand, also make medicine individual variation less, stability in the large is good, Losartan Potassium is easy to stripping.
Accompanying drawing explanation
Fig. 1 is the structured flowchart of preparation method of the present invention.
Detailed description of the invention
Below in conjunction with accompanying drawing embodiment, the present invention is described in further detail.
Embodiment 1:
As shown in Figure 1, the preparation method of the Losartan Tablet of the present embodiment comprises the following steps:
(1) each component proportion is designed: according to 1000 meters, the component of Losartan Tablet and content are
The particle diameter of above-mentioned Losartan Potassium is 10 μm≤d (0.1)≤19 μm, 54 μm≤d (0.5)≤87 μm, 135 μm≤d (0.9)≤234 μm;
(2) Losartan Potassium is crossed 60 mesh sieves, by mix homogeneously after lactose, microcrystalline Cellulose and pregelatinized Starch respectively mistake 40 mesh sieves;
(3) add in step (2) gained mixture after magnesium stearate being crossed 40 mesh sieves, tabletting after mix homogeneously, and coating.
Embodiment 2:
As shown in Figure 1, the preparation method of the Losartan Tablet of the present embodiment comprises the following steps:
(1) each component proportion is designed: according to 1000 meters, the component of Losartan Tablet and content are
The particle diameter of above-mentioned Losartan Potassium is 54 μm≤d (0.5)≤100 μm, 135 μm≤d (0.9)≤234 μm;
(2) Losartan Potassium is crossed 60 mesh sieves, by mix homogeneously after starch, carboxymethylstach sodium and pregelatinized Starch respectively mistake 40 mesh sieves;
(3) add in step (2) gained mixture after stearic acid being crossed 40 mesh sieves, tabletting after mix homogeneously, and coating.
Embodiment 3:
As shown in Figure 1, the preparation method of the Losartan Tablet of the present embodiment comprises the following steps:
(1) each component proportion is designed: according to 1000 meters, the component of Losartan Tablet and content are
The particle diameter of above-mentioned Losartan Potassium is 10 μm≤d (0.1)≤24 μm, 54 μm≤d (0.5)≤100 μm, 130 μm≤d (0.9)≤270 μm;
(2) Losartan Potassium is crossed 60 mesh sieves, by mix homogeneously after starch, carboxymethylstach sodium and pregelatinized Starch respectively mistake 40 mesh sieves;
(3) add in step (2) gained mixture after stearic acid being crossed 40 mesh sieves, tabletting after mix homogeneously, and coating.
Comparative example:
The preparation method of the Losartan Tablet of this comparative example comprises the following steps:
(1) each component proportion is designed: according to 1000 meters, the component of Losartan Tablet and content are
(2) Losartan Potassium is crossed 60 mesh sieves, lactose, microcrystalline Cellulose and pregelatinized Starch are crossed respectively 40 mesh sieves and be placed on premix in wet mixing pelletizer, then add the alcoholic solution granulation that volumetric concentration is 55%;
(3) granule prepared by step (2) is placed in fluid bed dry, arranging inlet temperature is 55 DEG C, and gained granule granulate is with rotating pelletizing machine granulate, mesh size 1.2mm;
(4) add in step (3) gained granule after magnesium stearate being crossed 40 mesh sieves, tabletting after mix homogeneously, and coating.
Measure the dissolving out capability of the Losartan Tablet that embodiment 1 is prepared with comparative example, concrete testing result is in table 1.According to dissolution method (Chinese Pharmacopoeia version in 2010 two annex XC second methods), with 900mL water for dissolution medium, rotating speed is 50 turns per minute, operate in accordance with the law, sample respectively at when 5min, 10min, 15min, 30min, 45min, get dissolution fluid appropriate, filter, it is appropriate that precision measures subsequent filtrate, the solution made about containing Losartan Potassium 20 μ g in every 1mL is quantitatively diluted with dissolution medium, according to Ultraviolet spectrophotometry (Chinese Pharmacopoeia version in 2010 two annex IV A), measure absorbance at the wavelength place of 256nm; Separately get Losartan Potassium reference substance appropriate, accurately weighed, add stripping medium dissolves and quantitatively dilute the solution made about containing 20 μ g in every 1mL, being measured in the same method, calculating stripping quantity.
Table 1
As can be seen from Table 1, the RSD numerical value of comparative example is obviously large than the numerical value of embodiment 1 sample, illustrate that the sample room diversity of employing wet granulation gained Losartan Tablet is comparatively large, and the sample room diversity of the Losartan Tablet that the present invention adopts powder vertical compression technique to prepare is less.
Test Losartan Tablet prepared by embodiment 1, test result is as shown in table 2.Comparative study is carried out in the Losartan Tablet prepare embodiment 1 and commercially available prod, study condition be 40 DEG C ± 2 DEG C, place 6 months under RH75% ± 5% condition, then the impurity content in principal agent is detected.Commercially available prod is buy the losartan (Losartan Tablet) produced by MSD Corp. from pharmacy.
Table 2
Can be found out by the comparative study result of table 2, the Losartan Tablet that the present invention obtains is 6 months in the acceleration time, and under accelerated test condition, stable content, related substance are without significant change, and comparatively commercially available prod is more stable.
Claims (9)
1. a preparation method for Losartan Tablet, is characterized in that comprising the following steps:
(1) each component proportion is designed: the component of described Losartan Tablet and content are
(2) by mix homogeneously after Losartan Potassium, filler, disintegrating agent and binding agent respectively mistake 40 ~ 60 mesh sieves;
(3) add in step (2) gained mixture after lubricant being crossed 40 ~ 50 mesh sieves, tabletting after mix homogeneously, and coating;
The particle diameter of above-mentioned Losartan Potassium is 54 μm≤d (0.5)≤107 μm, 125 μm≤d (0.9)≤278 μm.
2. the preparation method of Losartan Tablet according to claim 1, it is characterized in that: the particle diameter of described Losartan Potassium is 10 μm≤d (0.1)≤24 μm, 54 μm≤d (0.5)≤100 μm, 130 μm≤d (0.9)≤270 μm.
3. the preparation method of Losartan Tablet according to claim 2, it is characterized in that: the particle diameter of described Losartan Potassium is 10 μm≤d (0.1)≤19 μm, 54 μm≤d (0.5)≤87 μm, 135 μm≤d (0.9)≤234 μm.
4. the preparation method of Losartan Tablet according to claim 1, is characterized in that: described filler is one or more in starch, lactose, mannitol.
5. the preparation method of Losartan Tablet according to claim 1, is characterized in that: described disintegrating agent is one or more in microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, carboxymethylstach sodium.
6. the preparation method of Losartan Tablet according to claim 1, is characterized in that: described binding agent is one or more in pregelatinized Starch, hypromellose, hydroxypropyl cellulose.
7. the preparation method of Losartan Tablet according to claim 1, is characterized in that: described lubricant is one or more in magnesium stearate, stearic acid, sodium stearyl fumarate.
8. the preparation method of Losartan Tablet according to claim 1, is characterized in that: the component of described Losartan Tablet and content are
9. the preparation method of Losartan Tablet according to claim 8, is characterized in that: the component of described Losartan Tablet and content are
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510945518.7A CN105395509A (en) | 2015-12-16 | 2015-12-16 | Preparation method for losartan potassium tablet |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510945518.7A CN105395509A (en) | 2015-12-16 | 2015-12-16 | Preparation method for losartan potassium tablet |
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| CN105395509A true CN105395509A (en) | 2016-03-16 |
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| CN201510945518.7A Pending CN105395509A (en) | 2015-12-16 | 2015-12-16 | Preparation method for losartan potassium tablet |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1066184A (en) * | 1991-04-29 | 1992-11-18 | 麦克公司 | The tablet formulation of optimizing |
| WO2007026261A2 (en) * | 2005-05-18 | 2007-03-08 | Combino Pharm, S.L. | Formulations containing losartan and/or its salts |
| CN102276586A (en) * | 2010-06-09 | 2011-12-14 | 扬子江药业集团四川海蓉药业有限公司 | Preparation methods of losartan potassium and preparation thereof |
-
2015
- 2015-12-16 CN CN201510945518.7A patent/CN105395509A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1066184A (en) * | 1991-04-29 | 1992-11-18 | 麦克公司 | The tablet formulation of optimizing |
| WO2007026261A2 (en) * | 2005-05-18 | 2007-03-08 | Combino Pharm, S.L. | Formulations containing losartan and/or its salts |
| CN102276586A (en) * | 2010-06-09 | 2011-12-14 | 扬子江药业集团四川海蓉药业有限公司 | Preparation methods of losartan potassium and preparation thereof |
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Application publication date: 20160316 |
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