CN117503719A - Meisartan potassium tablet and preparation method thereof - Google Patents

Meisartan potassium tablet and preparation method thereof Download PDF

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CN117503719A
CN117503719A CN202311663314.5A CN202311663314A CN117503719A CN 117503719 A CN117503719 A CN 117503719A CN 202311663314 A CN202311663314 A CN 202311663314A CN 117503719 A CN117503719 A CN 117503719A
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potassium
metaxartan
dextrin
tablet
parts
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韩志鹏
张凤云
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Yantai Valiant Pharmaceutical Co ltd
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Yantai Valiant Pharmaceutical Co ltd
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    • 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
    • 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
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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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    • 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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Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to a losartan potassium tablet and a preparation method thereof. The preparation method comprises the following steps: uniformly mixing micronized metartan potassium with a glidant and dextrin to prepare a metaxartan potassium cyclodextrin inclusion compound; uniformly mixing the metaxartan potassium cyclodextrin inclusion compound with a filler and a disintegrating agent, adding a lubricant, uniformly mixing, and directly tabletting to obtain the metaxartan potassium tablet. The medicine of the metartan potassium tablet has fast dissolution, the medicine activity is kept stable, and the preparation method is suitable for industrial production.

Description

Meisartan potassium tablet and preparation method thereof
Technical Field
The invention relates to a losartan potassium tablet and a preparation method thereof, belonging to the technical field of pharmaceutical preparations.
Background
The metartan potassium is a precursor drug of azilsartan, also can be called as azilsartan potassium salt, can be hydrolyzed into azilsartan in gastrointestinal tract in the absorption process, is a blood pressure reducing drug developed by Japanese wuta medicines, belongs to an angiotensin II receptor inhibitor, and can block the vasoconstriction effect of angiotensin II by selectively blocking the combination of angiotensin II and vascular smooth muscle AT1 receptor, thereby achieving the effect of reducing blood pressure. Can well control blood pressure and reduce the risks of complicated cardiovascular diseases and diabetes.
When the losartan potassium is prepared into an oral preparation, the losartan potassium can be quickly dissolved in water to be well absorbed in the stomach and intestine, otherwise, the absorption and bioavailability of the losartan potassium are greatly hindered.
Chinese patent application CN101528262a discloses an azilsartan pharmaceutical composition with stable and excellent dissolution properties, which is characterized by containing an oil with low melting point and a binder with low viscosity, and is mainly characterized in that the dissolution of azilsartan is improved by using the binder with low viscosity. However, the use of low viscosity adhesives to enhance in vitro dissolution of azilsartan is often limited.
Chinese patent application CN103705510a discloses a method for preparing azilsartan solid composition, which is characterized in that azilsartan is prepared into suspension solution, then wet granulation is performed, and the suspension solution is added into auxiliary materials in an injection mode to prepare azilsartan preparation. Because the azilsartan structure contains amide bonds, the azilsartan structure is sensitive to humidity, and the adoption of wet granulation can lead to the great increase of azilsartan related substances, thereby affecting the medication safety.
Chinese patent application CN101677961a reports a solid preparation of azilsartan medoxomil potassium salt, and the pH environment in the preparation and release process is adjusted by adding a certain combination of pH control agent fumaric acid and sodium hydroxide, so as to improve the stability of the drug, but for azilsartan medoxomil, it is also necessary to accelerate the dissolution performance of the drug and increase the solubility.
Chinese patent application CN102138899a describes a liposome solid preparation of azilsartan medoxomil, which improves the stability of the drug by the protective action of the liposome. The closed structure of the liposome can protect the active ingredients of the medicine to a certain extent, but the liposome is easy to break in the preparation process, so that the medicine leaks, and the bioavailability is not high.
In the Chinese patent application, CN105456210A introduces a high-bioavailability azilsartan composition, which is prepared by mixing and micronizing azilsartan and a pharmaceutic adjuvant, so that the bioavailability of the azilsartan is improved, and the application of hydroxypropyl-beta-dextrin and a solubilizer are mentioned in the pharmaceutic adjuvant, wherein the hydroxypropyl-beta-dextrin has certain viscosity, and after being crushed, the viscosity is increased, so that the problems of uneven material mixing, tablet sticking, dissolution rate reduction and the like are easily caused; secondly, although the use of a solubilizing agent can promote dissolution, it often causes a certain irritation in the body, which is not favorable for clinical use. Therefore, it is very important to prepare the metartan potassium preparation which has fast dissolution, stable pharmaceutical activity and process suitability for industrial production.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention provides the losartan potassium tablet and the preparation method thereof, wherein the losartan potassium tablet is quick in drug dissolution and stable in drug activity, and the preparation method is suitable for industrial production.
The technical scheme for solving the technical problems is as follows: a potassium metaxartan tablet comprising micronized potassium metaxartan, a glidant, a dextrin, a filler, a disintegrant, and a lubricant.
Further, the metartan potassium tablet comprises, by weight: 23-24 parts of micronized metartan potassium; 2-3 parts of a glidant; 15-30 parts of dextrin; 35-50 parts of filler; 5-10 parts of disintegrating agent; 0.5-1.5 parts of lubricant.
Further, the micronized potassium metaxartan has a particle size D90 of not more than 40um.
Further, the glidant is any one or two of silicon dioxide and talcum powder.
Preferably, the glidant is silicon dioxide.
Further, the dextrin is any one or a combination of a plurality of alpha-dextrin, beta-dextrin and hydroxypropyl-alpha-dextrin.
Preferably, the dextrin is beta-dextrin.
Further, the filler is any one or a combination of a plurality of anhydrous lactose, corn starch, pregelatinized starch, microcrystalline cellulose and mannitol.
Preferably, the filler is microcrystalline cellulose and mannitol, wherein the microcrystalline cellulose is 20-45 parts by weight and the mannitol is 5-10 parts by weight.
Further, the disintegrating agent is any one of crospovidone, carboxypropyl cellulose and croscarmellose sodium.
Preferably, the disintegrant is croscarmellose sodium.
Further, the lubricant is any one or a combination of a plurality of magnesium stearate, talcum powder and polyethylene glycol.
Preferably, the lubricant is magnesium stearate.
The invention also discloses a preparation method of the metartan potassium tablet, which comprises the following steps:
s1, uniformly mixing micronized metaxartan potassium, a glidant and dextrin to prepare a metaxartan potassium cyclodextrin inclusion compound;
s2, uniformly mixing the metaxartan potassium cyclodextrin inclusion compound, the filler and the disintegrating agent, adding the lubricant, uniformly mixing, and directly tabletting to obtain the metaxartan potassium tablet.
The beneficial effects of the invention are as follows:
according to the invention, in the metartan potassium tablet and the preparation method, micronized metartan potassium is mixed with a proper amount of glidant and dextrin to prepare the metartan potassium cyclodextrin inclusion compound, and the inclusion compound can ensure the stability of the active ingredients of the medicine and promote the dissolution of the medicine in the preparation.
The micronized metartan potassium is favorable for dissolution, but the micronized metartan potassium is easy to have static electricity and can influence the processing process of tablets.
Detailed Description
The following describes the present invention in detail. The present invention may be embodied in many other forms than described herein and similarly modified by those skilled in the art without departing from the spirit of the invention, so that the invention is not limited to the specific embodiments disclosed.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
A potassium metaxartan tablet comprising micronized potassium metaxartan, a glidant, a dextrin, a filler, a disintegrant, and a lubricant.
Specifically, the metartan potassium tablet comprises, by weight: 23-24 parts of micronized metartan potassium; 2-3 parts of a glidant; 15-30 parts of dextrin; 35-50 parts of filler; 5-10 parts of disintegrating agent; 0.5-1.5 parts of lubricant.
Specifically, the micronized potassium metaxartan has a particle size D90 of not more than 40um.
Specifically, the glidant is any one or two of silicon dioxide and talcum powder.
More specifically, the glidant is silicon dioxide.
Specifically, the dextrin is any one or a combination of a plurality of alpha-dextrin, beta-dextrin and hydroxypropyl-alpha-dextrin.
More specifically, the dextrin is beta-dextrin.
Specifically, the filler is any one or a combination of a plurality of anhydrous lactose, corn starch, pregelatinized starch, microcrystalline cellulose and mannitol.
More specifically, the filler is microcrystalline cellulose and mannitol, wherein the microcrystalline cellulose is 20-45 parts by weight and the mannitol is 5-10 parts by weight.
Specifically, the disintegrating agent is any one of crospovidone, carboxypropyl cellulose and croscarmellose sodium.
More specifically, the disintegrant is croscarmellose sodium.
Specifically, the lubricant is any one or a combination of more than one of magnesium stearate, talcum powder and polyethylene glycol.
More specifically, the lubricant is magnesium stearate.
The invention also discloses a preparation method of the metartan potassium tablet, which comprises the following steps:
s1, uniformly mixing micronized metaxartan potassium, a glidant and dextrin to prepare a metaxartan potassium cyclodextrin inclusion compound;
s2, uniformly mixing the metaxartan potassium cyclodextrin inclusion compound, the filler and the disintegrating agent, adding the lubricant, uniformly mixing, and directly tabletting to obtain the metaxartan potassium tablet.
More specifically, the method of jet milling is used to micronize the potassium metartan to a particle size D90 of not more than 40um, wherein the jet milling conditions are as follows: the feed pressure was 0.3mpa and the pulverizing pressure was 0.5mpa.
Example 1
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Example 2
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Example 3
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Example 4
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Example 5
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Example 6
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Example 7
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and alpha-dextrin to prepare a metaxartan potassium-alpha-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Example 8
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and hydroxypropyl-alpha-dextrin to prepare a metaxartan potassium-hydroxypropyl-alpha-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tablet press.
Example 9
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with talcum powder and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Example 10
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with talcum powder and alpha-dextrin to prepare a metaxartan potassium-alpha-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of corn starch and crosslinked povidone, finally adding the prescribed amount of polyethylene glycol, uniformly mixing, and tabletting by a conventional tabletting machine.
Example 11
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and hydroxypropyl-alpha-dextrin to prepare a metaxartan potassium-hydroxypropyl-alpha-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and carboxypropyl cellulose, finally adding the prescribed amount of talcum powder, uniformly mixing, and tabletting by a conventional tabletting machine.
Comparative example 1
A potassium metaxartan tablet was prepared by the same method as in example 1 except that the amount of dextrin was reduced, and the specific composition was as shown in the following table:
the preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Comparative example 2
A potassium metaxartan tablet was prepared by the same method as in example 1 except that the amount of dextrin was increased, and the specific composition was as shown in the following table:
the preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Comparative example 3
A potassium metaxartan tablet was prepared by the same method as in example 1 except that the amount of the glidant silicon dioxide was reduced, and the specific composition thereof was as follows:
the preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide and beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Comparative example 4
A potassium metaxartan tablet was prepared by the same method as in example 1 except that dextrin was not added, and the specific composition was as follows:
the preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with silicon dioxide, mannitol, microcrystalline cellulose and croscarmellose sodium uniformly, adding the prescribed amount of magnesium stearate, mixing uniformly, and tabletting by a conventional tablet press.
Comparative example 5
A potassium metaxartan tablet was prepared by the same method as in example 1 except that no glidant silica was added, and the specific composition is as follows:
the preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
Comparative example 6
A potassium metaxartan tablet was prepared by the same method as in example 1 except that metaxartan potassium (micronized) was first mixed with beta-dextrin to prepare a clathrate, and then glidant silicon dioxide was added.
The preparation method comprises the following steps:
mixing the prescribed amount of metaxartan potassium (micronization) with beta-dextrin to prepare a metaxartan potassium-beta-dextrin inclusion compound, uniformly mixing the inclusion compound with the prescribed amount of silicon dioxide, mannitol, microcrystalline cellulose and croscarmellose sodium, finally adding the prescribed amount of magnesium stearate, uniformly mixing, and tabletting by a conventional tabletting machine.
1. The related properties of the metartan potassium tablets obtained in the above examples and comparative examples were measured, and the specific results are shown in table 1 below.
Table 1 results of testing the properties related to the potassium mesartan tablets
Remarks: in table 1, the criteria for mixing uniformity are: sampling from 6 positions of the total mixed powder respectively, and measuring the content, wherein the RSD value is less than or equal to 5.0%; the disintegration time was measured by taking 900ml of a deaerated phosphate buffer (pH 7.8) as a dissolution medium at a rotation speed of 50 rpm, and recording the total disintegration time of the tablet.
From the data in table 1, it can be seen that the metartan potassium tablets prepared by the preparation method of examples 1-11 have good appearance, rapid disintegration and good content uniformity of main drugs.
From comparison of experimental data of comparative example 1 and example 1, it can be seen that if the amount of dextrin is reduced, the disintegration time is increased.
As can be seen from comparison of experimental data of comparative example 2 and example 1, when the amount of beta-dextrin is increased, the problems of non-uniform content, sticking and punching of tablets, and increased disintegration time occur.
As can be seen from comparison of experimental data of comparative example 3 and example 1, if the amount of the glidant silicon dioxide is reduced, the problem of non-uniformity of content occurs and the problem of an increase in disintegration time occurs.
As can be seen from comparison of the experimental data of comparative example 4 and example 1, the disintegration time is increased if dextrin is not added.
From comparison of the experimental data of comparative example 5 and example 1, it can be seen that severe sticking phenomenon occurs during tabletting when no glidant silica is added.
From comparison of experimental data of comparative example 6 and example 1, it can be seen that if silicon dioxide is added after preparation of the metaxartan potassium cyclodextrin inclusion compound during preparation of the metaxartan potassium tablet, the problem of non-uniform content occurs, the tablet surface is rough, the sticking problem occurs during tabletting, and the disintegration time is increased.
2. Determination of dissolution
The potassium metaxartan tablets prepared in the above examples and comparative examples were subjected to dissolution and release rate measurement (second method of CP general rule 0931) using 900ml of deaerated phosphate buffer (ph 7.8) as a dissolution medium at 50 rpm, and the dissolution rates were measured for 5 minutes, 10 minutes, 15 minutes and 20 minutes in the medium according to the method, and the specific results are shown in table 2 below.
TABLE 2 measurement results of dissolution
As can be seen from the data in the above Table 2, the dissolution rate of the losartan potassium tablets prepared by the preparation method of examples 1 to 11 is high, and the dissolution rate of 20min is above 90%.
From comparison of experimental data of comparative example 1 and example 1, it can be seen that if the amount of dextrin is reduced, dissolution is reduced.
As can be seen from comparison of experimental data of comparative example 2 and example 1, as the amount of beta-dextrin increases, the dissolution rate of the tablet at each time point is significantly reduced, because the cyclodextrin effect is too strong, and dissolution of the raw material potassium metartan is suppressed.
As a result of comparison of the experimental data of comparative examples 3, 5, 6 and 1, respectively, if the amount of the glidant silica is reduced or no silica is added or the glidant silica is added after inclusion compound, the dissolution rate of the tablet at each time point is also reduced because the silica can sufficiently disperse the potassium metartan, prevent the binding and also play a role in promoting dissolution to some extent.
3. Meisartan potassium tablet stability measurement (test for detecting substances related to Meisartan potassium tablet before and after accelerated test)
Taking the metaxartan potassium tablets prepared in the above examples 1-9 and comparative example 4 as samples, packaging with aluminum foil for drug packaging and polyvinyl chloride solid pharmaceutical hard sheet (plus composite film bag package and desiccant), and performing an acceleration test for 6 months under the acceleration test conditions: detecting related substances at the temperature of 40+/-2 ℃ and the relative humidity of 75+/-5% in 0 month and 6 months respectively;
the relevant substances in the tablets were detected by conventional HPLC methods as follows:
the checking method comprises the following steps: HPLC method.
Chromatographic conditions:
chromatographic column: dodecyl silane bonded silica gel is used as filler (YMC-Pack Pro C18 column; 4.6X105 mm,5 μm or column chromatography column with equivalent column effect)
Detection wavelength: sample injection amount of 10 μl at 240nm
Column temperature: 5 DEG C
Flow rate: 1.0ml per minute.
Mobile phase a:0.05mol/L phosphate buffer (pH 3.0) -acetonitrile (19:1, v/v); mobile phase B: acetonitrile-0.05 mol/L phosphate buffer (pH 3.0) (7:3, v/v).
The gradient elution conditions were:
the results of the accelerated test for the tablets of examples 1-9 and comparative examples 1 and 4 are shown in Table 3.
Table 3 examples 1-9 and comparative example 1, comparative example 4 results of tablet acceleration test detection
From the results of the accelerated test shown in Table 3, in the metartan potassium tablets prepared in examples 1 to 9 of the present invention, the raw materials were all included by cyclodextrin, and the related substances were not significantly changed in the test of the accelerated test for 6 months. In the mesartan potassium tablets prepared in comparative examples 1 and 4, when the amount of cyclodextrin in the formulation was reduced or cyclodextrin was not added, the substances involved were significantly changed in the test of accelerating the test for 6 months.
In conclusion, the experimental data show that the metaxartan potassium tablet has the advantages of excellent appearance, faster disintegration, good content uniformity of main medicine and good dissolution rate and stability.
The technical features of the above-described embodiments may be arbitrarily combined, and in order to simplify the description, all possible combinations of the technical features in the above-described embodiments are not exhaustive, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention as defined in the appended claims.

Claims (10)

1. A potassium metaxartan tablet, characterized in that it comprises micronized potassium metaxartan, a glidant, a dextrin, a filler, a disintegrant and a lubricant.
2. The metaxartan potassium tablet according to claim 1, wherein the metaxartan potassium tablet comprises, in parts by weight: 23-24 parts of micronized metartan potassium; 2-3 parts of a glidant; 15-30 parts of dextrin; 35-50 parts of filler; 5-10 parts of disintegrating agent; 0.5-1.5 parts of lubricant.
3. A potassium metaxartan tablet according to claim 1 or 2 wherein the micronized potassium metaxartan has a particle size D90 of not more than 40um.
4. A metaxartan potassium tablet according to claim 1 or 2 wherein the glidant is any one or a mixture of two of silica and talc.
5. A metaxartan potassium tablet according to claim 1 or 2, wherein the dextrin is any one or a combination of a plurality of alpha-dextrin, beta-dextrin, hydroxypropyl-alpha-dextrin.
6. A potassium metaxartan tablet according to claim 1 or 2, wherein the filler is any one or a combination of several of anhydrous lactose, corn starch, pregelatinized starch, microcrystalline cellulose and mannitol.
7. The metaxartan potassium tablet according to claim 6, wherein the filler is microcrystalline cellulose and mannitol, and the microcrystalline cellulose is 20-45 parts by weight and the mannitol is 5-10 parts by weight.
8. A metaxartan potassium tablet according to claim 1 or 2, wherein the disintegrant is any one of crospovidone, carboxypropyl cellulose and croscarmellose sodium.
9. A metaxartan potassium tablet according to claim 1 or 2 wherein the lubricant is any one or a combination of magnesium stearate, talc and polyethylene glycol.
10. A process for the preparation of a tablet of potassium metartan according to any one of claims 1 to 9, characterized in that it comprises:
s1, uniformly mixing micronized metaxartan potassium, a glidant and dextrin to prepare a metaxartan potassium cyclodextrin inclusion compound;
s2, uniformly mixing the metaxartan potassium cyclodextrin inclusion compound, the filler and the disintegrating agent, adding the lubricant, uniformly mixing, and directly tabletting to obtain the metaxartan potassium tablet.
CN202311663314.5A 2023-12-06 2023-12-06 Meisartan potassium tablet and preparation method thereof Pending CN117503719A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118121598A (en) * 2024-03-01 2024-06-04 浙江大学 Stable pharmaceutical composition of losartan potassium, and preparation method and application thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118121598A (en) * 2024-03-01 2024-06-04 浙江大学 Stable pharmaceutical composition of losartan potassium, and preparation method and application thereof

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