CN113133978B - Azilsartan tablets and preparation method thereof - Google Patents
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Abstract
The invention provides an azilsartan tablet which is prepared from polyethylene glycol glyceride stearate; the azilsartan tablet prepared by the method has higher solubility and stability. In addition, the preparation process provided by the invention is simple and efficient, the azilsartan raw material does not need micronization treatment or dissolution by using an organic solvent, so that the process steps can be reduced, and the environment protection is facilitated; the preparation process does not contact with excessive water, so that the degradation of the azilsartan in a high-humidity environment can be effectively avoided, and the prepared azilsartan tablet has good stability.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an azilsartan medoxomil tablet, a preparation method thereof and application thereof in treating diseases such as hypertension and the like.
Background
Azilsartan (english name Azilsartan) is an angiotensin II receptor antagonist drug for treating hypertension, which blocks the vasoconstrictor effect of angiotensin II by selectively blocking the binding of angiotensin II to vascular smooth muscle AT1 receptor, and is widely used for treating hypertension. The prodrug azilsartan medoxomil is FDA approved in 2011 for 25 months and is chemically named 2-ethoxy-1- [ [2' - (4, 5-dihydro-5-oxo-1, 2, 4-oxadiazol-3-yl) biphenyl-4-yl ] methyl ] benzimidazole-7-carboxylic acid. The azilsartan is approved for use in 18 days of 1 month 2012, and the azilsartan is taken orally, once daily, and can be used alone or together with other antihypertensive drugs. Azilsartan medoxomil is hydrolyzed to the active metabolite azilsartan in the gastrointestinal tract during absorption. Clinical test results show that compared with common similar antihypertensive drugs valsartan and olmesartan, azilsartan has better antihypertensive effect within 24 hours.
However, azilsartan is hardly soluble in water, and is a poorly soluble drug, and its solubility in water is about 6mg/L (20 ℃). Generally, the oral bioavailability of poorly soluble drugs is low, and although more attempts can be made to improve the bioavailability, improving the dissolution of the drug is an effective way to improve the bioavailability. Therefore, the solubility of the compound is improved through a preparation technology to meet the requirements of dissolution and stability, so that the product is ensured to effectively play the therapeutic role, and the preparation method has very important significance and value.
Patent document CN104306344a discloses an azilsartan tablet and a preparation method thereof, wherein the azilsartan tablet is prepared by compressing azilsartan, microcrystalline cellulose, KG1000 and other pharmaceutically acceptable auxiliary materials by adopting a dry direct tabletting process. Although the introduction of moisture can be effectively avoided, the stability of the product is ensured, the azilsartan before mixing needs micronization treatment, so that the process steps are increased to a certain extent, and a certain dust influence is generated on the production environment.
Patent document CN104523632a discloses an azilsartan tablet, which is prepared by dissolving azilsartan and povidone in diethylene glycol ethyl ether, adding silicon dioxide for adsorption, and then mixing with other auxiliary materials for direct compression. However, the azilsartan tablets are directly pressed by adopting powder, the process is simple, the uniformity of mixing is difficult to ensure, layering is easy to generate in the tabletting process, and the problem of in-vitro dissolution is not essentially solved.
Patent document CN106333930a discloses an azilsartan pellet tablet and a preparation method thereof, the azilsartan pellet tablet is formed by tabletting azilsartan pellets and pharmaceutic adjuvant, the dissolution rate and bioavailability of the drug are improved, but the azilsartan pellet tablet may undergo crystal form transformation in the preparation process of fluidized bed pellets, and in addition, the process step is complex, and the azilsartan pellet tablet is difficult to be applied to industrial production.
Therefore, although many documents disclose preparation products for improving the solubility of azilsartan and a preparation method thereof, there are more or less disadvantages, and for azilsartan preparation products with a large market demand, continuous researches are still needed to provide preparation products with excellent biocompatibility and efficacy and a convenient and efficient preparation process suitable for industrialization.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide the azilsartan tablet with better dissolution characteristic, higher stability and simple and efficient preparation process. Through a great number of creative thinking and experiments, the inventor finds that the dissolution of the azilsartan medoxomil tablet can be obviously improved by adding water-dispersible granule polyethylene glycol stearate into a prescription, but the azilsartan medoxomil tablet still does not reach an ideal state, and further finds that the dissolution of the azilsartan medoxomil tablet can be obviously improved by adding a preparation obtained by tabletting pharmaceutically acceptable auxiliary materials into the preparation which is granulated together with the polyethylene glycol stearate. The absorption part of the azilsartan medoxomil in the intestinal tract is mainly jejunum, the physiological pH of jejunum is 5.5-7.0, and the azilsartan medoxomil can be completely dissolved out in buffer solution with pH of 6.0, so that the optimal absorption and utilization effects of the medicine can be ensured.
In the research process of the preparation process, although the dissolution rate is improved by crushing the medicine and the auxiliary materials together, the method sacrifices the fluidity of the particles, the particle weight is possibly unstable during filling, and meanwhile, the medicine particles are easy to aggregate, so the process is not selected. The fluidized bed technology and the staged feeding mode can be used for not only keeping the fluidity of particles, but also avoiding the problem of uneven mixing, and the obtained tablet product has better dissolution characteristic.
The specific technical content of the invention is as follows:
in one aspect, the invention provides an azilsartan medoxomil tablet which is characterized by comprising azilsartan, polyethylene glycol glyceride stearate and pharmaceutically acceptable auxiliary materials.
Preferably, the weight ratio of azilsartan to polyethylene glycol glyceride stearate in the azilsartan medoxomil tablet is 1:1-3; preferably in a weight ratio of 1:2.
Preferably, the pharmaceutically acceptable auxiliary materials are filler, disintegrating agent and lubricant.
Further preferably, the filler is one or a combination of mannitol, microcrystalline cellulose, lactose, starch, dextrin and polyethylene glycol; mannitol is preferred; the weight ratio of the azilsartan to the filler is 1:2 to 10, preferably 1:3 to 5.
Further preferably, the disintegrating agent is one or a combination of sodium carboxymethyl starch, croscarmellose sodium, crospovidone and low-substituted hydroxypropyl cellulose; preferably low-substituted hydroxypropyl cellulose; the weight ratio of the azilsartan to the disintegrating agent is 1:0.1 to 1, preferably 1:0.2 to 0.5.
Further preferably, the lubricant is one or a combination of hydrogenated castor oil, sodium stearate, talcum powder and magnesium stearate; magnesium stearate is preferred; the weight ratio of the azilsartan to the lubricant is 1:0.01 to 0.5; preferably 1:0.05 to 0.1.
Preferably, the azilsartan medoxomil tablet comprises the following components:
further preferably, the azilsartan medoxomil tablet comprises the following components:
on the other hand, the invention provides a preparation method of azilsartan medoxomil tablets, which comprises the following specific preparation processes:
adding the azilsartan and part of the stearic acid polyethylene glycol glyceride with the prescription amount into a fluidized bed, melting and heating, and performing melt granulation in the fluidized bed; immediately adding the filler, the disintegrating agent and the rest of the stearic acid polyethylene glycol glyceride after melt granulation, continuously granulating, finishing hot granulating after granulating, adding the lubricant, and tabletting to obtain the azilsartan tablets.
Preferably, the part of the stearic acid polyethylene glycol glyceride accounts for 50-60% of the prescription amount.
Preferably, the temperature of the melting heat is 45-60 ℃, preferably 50 ℃.
Preferably, the time of the melt granulation is 3-7 min.
Compared with the prior art, the invention has the following advantages:
(1) The azilsartan medoxomil tablet is prepared by using the polyethylene glycol glyceride stearate, has high dissolution speed in a buffer solution with the pH value of 6.0, and has higher bioavailability.
(2) The azilsartan medoxomil tablet prepared by the method has higher solubility, and the dissolution rate after an acceleration test is still more than 98%, so that the azilsartan medoxomil tablet has better dissolution and stability.
(3) The preparation process provided by the invention is simple and efficient, the azilsartan raw material does not need micronization treatment or dissolution by using an organic solvent, the process steps can be reduced, and the environment protection is facilitated.
(4) The preparation process provided by the invention is not contacted with redundant water, so that the generation of the degradation of the azilsartan in a high-humidity environment can be effectively avoided, and the prepared azilsartan tablet has better stability.
Detailed Description
The invention is further illustrated by the following examples, with the understanding that: the examples of the present invention are intended to be illustrative of the invention and not limiting thereof, so that simple modifications of the invention based on the method of the invention are within the scope of the invention as claimed.
Example 1
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 20g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; melting and granulating for 5min, immediately adding mannitol, low-substituted hydroxypropyl cellulose and the rest 20g of polyethylene glycol glyceride stearate, continuously granulating for 5min, sieving the granules with a 20-mesh sieve while hot after granulating, adding magnesium stearate, mixing uniformly, tabletting to obtain the azilsartan tablet, wherein the tablet has complete and smooth appearance and uniform color.
Example 2
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 10g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; and (3) performing melt granulation for 3min, immediately adding 10g of mannitol, low-substituted hydroxypropyl cellulose and the rest of polyethylene glycol glyceride stearate, continuously granulating for 8min, sieving the granules with a 20-mesh sieve while hot after granulating, adding magnesium stearate, uniformly mixing, and tabletting to obtain the azilsartan tablet, wherein the tablet has complete and smooth appearance and uniform color.
Example 3
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 30g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 60 ℃, and carrying out melt granulation in the fluidized bed; and (3) performing melt granulation for 7min, immediately adding 30g of mannitol, low-substituted hydroxypropyl cellulose and the rest of polyethylene glycol glyceride stearate, continuously granulating for 3min, sieving the granules with a 20-mesh sieve while hot after granulating, adding magnesium stearate, uniformly mixing, and tabletting to obtain the azilsartan tablet, wherein the tablet has complete and smooth appearance and uniform color.
Example 4
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 20g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; melt granulating for 5min, immediately adding lactose, crosslinked povidone and the rest of polyethylene glycol glyceride stearate 20g, continuously granulating for 5min, sieving with a 20-mesh sieve while hot after granulating, adding hydrogenated castor oil, mixing uniformly, tabletting to obtain azilsartan tablets, and making the tablets complete and smooth in appearance and uniform in color.
Example 5
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 20g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; and (3) performing melt granulation for 5min, immediately adding 20g of starch, crosslinked sodium carboxymethylcellulose and the rest of polyethylene glycol glyceride stearate, continuously granulating for 3min, sieving the granules with a 20-mesh sieve while hot after the granulating is finished, adding sodium stearate fumarate, uniformly mixing, and tabletting to obtain the azilsartan tablet, wherein the tablet has complete and smooth appearance and uniform color.
Example 6
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 12g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; and (3) performing melt granulation for 3min, immediately adding microcrystalline cellulose, sodium carboxymethyl starch and the rest 8g of polyethylene glycol glyceride stearate, continuously granulating for 5min, sieving the granules with a 20-mesh sieve while hot after granulating, adding talcum powder, uniformly mixing, and tabletting to obtain the azilsartan tablet, wherein the tablet has complete and smooth appearance and uniform color.
Example 7
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 5g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 45 ℃, and carrying out melt granulation in the fluidized bed; melting and granulating for 3min, immediately adding mannitol, low-substituted hydroxypropyl cellulose and 5g of the rest polyethylene glycol glyceride stearate, continuously granulating for 3min, sieving the granules with a 20-mesh sieve while hot after granulating, adding magnesium stearate, mixing uniformly, and tabletting to obtain the azilsartan tablet, wherein the tablet has complete and smooth appearance and uniform color.
Example 8
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 20g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; melting and granulating for 3min, immediately adding mannitol, low-substituted hydroxypropyl cellulose and the rest 20g of polyethylene glycol glyceride stearate, continuously granulating for 3min, sieving the granules with a 20-mesh sieve while hot after granulating, adding magnesium stearate, mixing uniformly, tabletting to obtain azilsartan tablets, wherein the tablet has complete appearance, few cracks and nonuniform color.
Example 9
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 28g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; melting and granulating for 5min, immediately adding mannitol, low-substituted hydroxypropyl cellulose and the rest of polyethylene glycol glyceride stearate 12g, continuously granulating for 5min, sieving the granules with a 20-mesh sieve while hot after granulating, adding magnesium stearate, mixing uniformly, tabletting to obtain azilsartan tablets, wherein the tablet has complete appearance, few cracks and nonuniform color.
Example 10
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 16g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; melting and granulating for 5min, immediately adding mannitol, low-substituted hydroxypropyl cellulose and the rest of polyethylene glycol glyceride stearate 24g, continuously granulating for 5min, sieving the granules with a 20-mesh sieve while hot after granulating, adding magnesium stearate, mixing uniformly, and tabletting to obtain the azilsartan tablet, wherein the tablet has complete appearance, few cracks and nonuniform color.
Example 11
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 20g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; melting and granulating for 5min, immediately adding pregelatinized starch, crosslinked polyvinylpyrrolidone and the rest of polyethylene glycol glyceride stearate (20 g), continuously granulating for 5min, sieving with a 20-mesh sieve while hot after granulating, adding micropowder silica gel, mixing uniformly, tabletting to obtain azilsartan tablets, wherein the tablet has good appearance and cracks.
Example 12
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 20g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; melting and granulating for 5min, immediately adding sorbitol, sodium alginate and the rest of polyethylene glycol glyceride stearate 20g, continuously granulating for 5min, sieving the granules with a 20-mesh sieve while hot after granulating, adding magnesium stearate, mixing uniformly, tabletting to obtain azilsartan tablets, wherein the tablet has good overall appearance and cracks.
Example 13
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 10g of polyethylene glycol glyceride stearate with the prescription amount into a fluidized bed, setting the temperature to be 50 ℃, and carrying out melt granulation in the fluidized bed; melting and granulating for 5min, immediately adding mannitol, low-substituted hydroxypropyl cellulose and the rest of polyethylene glycol glyceride stearate (10 g), continuously granulating for 5min, sieving with a 20-mesh sieve to obtain granule, adding magnesium stearate, mixing, tabletting to obtain azilsartan tablets, and making the tablet have complete and smooth appearance and uniform color.
Comparative example 1 (prescription stearic acid-free polyethylene glycol glyceride)
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. The azilsartan tablet is prepared by uniformly mixing the prescription amount of azilsartan, anhydrous direct-compression lactose, mannitol and low-substituted hydroxypropyl cellulose, then adding magnesium stearate, uniformly mixing, and tabletting, wherein the tablet has good overall appearance and cracks.
Comparative example 2 (preparation Process, wet mixing)
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. The preparation method comprises the steps of uniformly mixing the azilsartan, the polyethylene glycol glyceride stearate, the mannitol and the low-substituted hydroxypropyl cellulose according to the prescription amount, preparing a soft material by using 40ml of 5% hydroxypropyl cellulose aqueous solution, sieving with a 20-mesh sieve, granulating, drying at 40 ℃ for 1h, adding sodium stearate, uniformly mixing, tabletting to obtain the azilsartan tablet, wherein the tablet has good overall appearance and cracks.
Comparative example 3
The preparation process comprises the following steps: azilsartan is micronized for later use. The azilsartan tablet is prepared by uniformly mixing the prescription amount of azilsartan, anhydrous direct-compression lactose, mannitol and low-substituted hydroxypropyl cellulose, then adding magnesium stearate, uniformly mixing, and tabletting, wherein the tablet has good overall appearance and cracks.
Comparative example 4
The preparation process comprises the following steps: pulverizing azilsartan, and sieving with 80 mesh sieve. Adding azilsartan and 25g of poloxamer 407 with the prescription amount into a fluidized bed, setting the temperature to be 45 ℃, and performing melt granulation in the fluidized bed; melting and granulating for 5min, immediately adding mannitol, crosslinked povidone and the rest of poloxamer 407, continuously granulating for 5min, sieving the granules with a 20-mesh sieve while hot after granulating, adding magnesium stearate, mixing uniformly, tabletting to obtain azilsartan tablets, and obtaining the azilsartan tablets with complete and smooth appearance and uniform color.
Comparative example 5
The preparation process comprises the following steps: the azilsartan is subjected to jet milling, the prescription amount is weighed and fed, then the azilsartan is uniformly mixed with the prescription amount of microcrystalline cellulose KG1000 in a mixer, the prescription amount of crospovidone, lactose 80 and magnesium stearate are added and uniformly mixed, and the azilsartan tablet is obtained by tabletting, so that the tablet has a good overall appearance.
Dissolution measurement
The dissolution rate measurement is carried out according to the second method of the four appendices 0931 of the 2015 edition of Chinese pharmacopoeia, specifically: 900ml of phosphate buffer solution with pH of 6.0 is taken as a dissolution medium, the rotation speed is 50 revolutions per minute, 10ml is sampled at 15 minutes according to the law, 5ml of the subsequent filtrate is filtered, the filtrate is placed in a 10ml volumetric flask, the phosphate buffer solution with pH of 6.0 is added for dilution to a scale, shaking is carried out, the mixture is taken as a sample solution, and the absorbance is measured at 247nm wavelength according to an ultraviolet-visible spectrophotometry (four appendices 0401 of China pharmacopoeia 2015). And (3) dissolving a proper amount of azilsartan reference substance in methanol, diluting to prepare a solution containing about 1mg per 1ml, precisely measuring 1ml, placing into a 100ml volumetric flask, adding phosphate buffer solution with pH of 6.0, diluting to a scale, shaking uniformly, and measuring by the same method. The dissolution rate of each tablet was calculated to be not less than 75%.
TABLE 1 Azilsartan tablet dissolution test results
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The experimental results show that the azilsartan medoxomil tablet prepared by the invention has rapid dissolution, the dissolution rate of 15min is over 99 percent, and the azilsartan medoxomil tablet still maintains good dissolution characteristics after an acceleration experiment.
Stability investigation
And (3) detecting related substances: taking 20 pieces of the product, grinding, taking a proper amount of fine powder (about equivalent to 10mg of azilsartan), putting into a 20ml brown measuring flask, adding methanol to dissolve and dilute to scale, shaking uniformly, filtering, and taking the subsequent filtrate as a sample solution; 1ml of the sample solution is precisely measured, placed in a 100ml brown measuring flask, diluted to a scale by adding methanol, and shaken uniformly to serve as a control solution. High performance liquid chromatography (China pharmacopoeia 2010 edition two appendix VD) is adopted for testing. Octadecylsilane chemically bonded silica is used as a filler; the mobile phase A was pH3.0 buffer (1.36 g of potassium dihydrogen phosphate and 1.74g of sodium pentanesulfonate were weighed, dissolved in 1000ml of water, pH was adjusted to 3.0 with phosphoric acid), and the mobile phase B was acetonitrile, and subjected to linear gradient elution at a detection wavelength of 251nm. Weighing impurity 1, impurity 2, impurity 3, impurity 4, impurity 5 and azilsartan reference substances in proper amounts respectively, adding methanol for dissolving and diluting to prepare a solution containing about 0.5mg of azilsartan per 1ml, wherein 5 mug of known impurities are used as a system test solution; and (3) 10 mu l of the system test solution is precisely measured and injected into a liquid chromatograph, a chromatogram is recorded, and peaks are sequentially formed from impurity 2, impurity 1, azilsartan, impurity 3, impurity 5 and impurity 4, wherein the separation degree among the peaks of all substances meets the requirement. Injecting 10 μl of control solution into a liquid chromatograph, and adjusting detection sensitivity to make the peak height of the main component chromatographic peak be 10% -25% of full range; then, 10 μl of each of the sample solution and the control solution was measured precisely and injected into the liquid chromatograph, and the chromatograms were recorded. After subtracting the solvent peak, there are impurity peaks in the chromatogram of the sample solution, wherein the peak areas of impurity 2 and impurity 5 are not more than 0.5 times (0.5%) of the main peak area of the control solution, the peak areas of impurity 1, impurity 3 and impurity 4 are not more than 0.2 times (0.2%) of the main peak area of the control solution, the peak areas of other maximum single impurities are not more than 0.2 times (0.2%) of the main peak area of the control solution, and the sum of the peak areas of all impurities is not more than 1.5 times (1.5%) of the main peak area of the control solution.
Table 2 results of azilsartan tablet stability experiments
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The experimental results show that the azilsartan related substances prepared by the method have small total impurities, and the related substances are basically unchanged after all the examples are subjected to the acceleration experiment, so that the method has good stability.
Claims (3)
1. The azilsartan tablet is characterized by comprising azilsartan and polyethylene glycol glyceride stearate, wherein the weight ratio of the azilsartan to the polyethylene glycol glyceride stearate is 1:1-3, the tablet also comprises pharmaceutically acceptable auxiliary materials, the auxiliary materials are filler, disintegrant and lubricant, the filler is selected from one of mannitol, microcrystalline cellulose, lactose and starch, the disintegrant is selected from one of sodium carboxymethyl starch, sodium crosslinked carboxymethyl cellulose, crosslinked povidone and low-substituted hydroxypropyl cellulose or a combination thereof, and the lubricant is selected from one of magnesium stearate, hydrogenated castor oil, sodium stearate, talcum powder and silicon dioxide or a combination thereof;
the specific preparation process comprises the following steps: adding the azilsartan and part of the stearic acid polyethylene glycol glyceride with the prescription amount into a fluidized bed, melting and heating, and performing melt granulation in the fluidized bed; immediately adding a filler, a disintegrating agent and the rest of stearic acid polyethylene glycol glyceride after melt granulation, continuously granulating, finishing hot granulating after granulating, adding a lubricant, and tabletting to obtain azilsartan tablets;
part of the stearic acid polyethylene glycol glyceride in the preparation process is 50-60% of the prescription amount.
2. The tablet of claim 1, wherein the temperature of the melt heating in the manufacturing process is 45 to 60 ℃.
3. The tablet according to claim 1, wherein the time of melt granulation in the preparation process is 3 to 7 minutes.
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| CN102046154A (en) * | 2008-06-03 | 2011-05-04 | 诺瓦提斯公司 | Pulsatile release of valsartan |
| CN105708809A (en) * | 2015-05-09 | 2016-06-29 | 张秋野 | Hot-melt granulation method of pharmaceutical adjuvant of controlled/slow-released agent |
| CN106176604A (en) * | 2016-08-30 | 2016-12-07 | 佛山市弘泰药物研发有限公司 | A kind of Azilsartan potassium salt self-micro emulsion formulation and preparation method thereof |
| CN106389428A (en) * | 2016-10-11 | 2017-02-15 | 上海现代制药股份有限公司 | Composition capable of improving Azilsartan bioavailability and stability and preparation method of composition |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102046154A (en) * | 2008-06-03 | 2011-05-04 | 诺瓦提斯公司 | Pulsatile release of valsartan |
| CN105708809A (en) * | 2015-05-09 | 2016-06-29 | 张秋野 | Hot-melt granulation method of pharmaceutical adjuvant of controlled/slow-released agent |
| CN106176604A (en) * | 2016-08-30 | 2016-12-07 | 佛山市弘泰药物研发有限公司 | A kind of Azilsartan potassium salt self-micro emulsion formulation and preparation method thereof |
| CN106389428A (en) * | 2016-10-11 | 2017-02-15 | 上海现代制药股份有限公司 | Composition capable of improving Azilsartan bioavailability and stability and preparation method of composition |
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| CN113133978A (en) | 2021-07-20 |
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