CN106580909B - Solid pharmaceutical composition containing sarpogrelate hydrochloride - Google Patents
Solid pharmaceutical composition containing sarpogrelate hydrochloride Download PDFInfo
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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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- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
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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
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Abstract
The invention relates to a sarpogrelate hydrochloride oral solid composition, a preparation process and application thereof. The sarpogrelate hydrochloride coated tablet is obtained by screening the components and the dosage of each auxiliary material in the preparation, the obtained tablet is proper in disintegration, and the indexes of hardness, friability and the like all meet the requirements of a coating process, and the sarpogrelate hydrochloride coated tablet has the characteristics of simple production process, convenience in production, stable quality and the like.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a sarpogrelate hydrochloride oral solid composition, and a preparation process and application thereof.
Background
Sarpogrelate hydrochloride (sarpogrelate hydrochloride) is a 5-hydroxytryptamine (5-HT2) receptor blocker, and can specifically bind to 5-HT2 receptor. 5-hydroxytryptamine (5-HT) was first proposed as a vasoactive substance in 1955. 5-HT is widely present in animals, particularly in the cardiovascular system, and almost all but a small fraction of 5-HT is inactivated by liver and lung endothelial cells, with the exception of platelets which are reabsorbed and stored in the blood. The sarpogrelate hydrochloride can be specifically combined with 5-HT2 receptor, and shows special antagonism to the receptor on platelet and vascular smooth muscle. Therefore, the compound has the effects of resisting platelet and inhibiting vasoconstriction, and plays a series of biological effects. The sarpogrelate hydrochloride is an antithrombotic drug, is mainly used for improving ischemic symptoms such as ulcer, pain and cold caused by chronic arterial occlusion, and treating diabetic complications. These effects are clinically used for treating vascular diseases such as peripheral vascular diseases and chronic ischemic vascular occlusion.
The sarpogrelate hydrochloride tablet is an imitation original medicine Annelek, the sarpogrelate hydrochloride tablet is marketed by Mitsubishi pharmaceutical company in Japan in 7 months 1993, and the tablet is approved to be imported in 1998 in China, so that administrative protection is obtained, and the administrative protection is expired at present. The patent of the drug is due at the end of 4 months in 2006, but no imitation drug of the drug is declared by domestic enterprises at present. With the improvement of living standard and the arrival of aging society, chronic arterial occlusion is a common middle-aged and old-aged vascular disease, the incidence rate of the chronic arterial occlusion is on the rise, and the market has vigorous demand for medicines for treating the chronic arterial occlusion. The drugs used in the past simply inhibit platelet aggregation and have poor selectivity or simply dilate blood vessels.
The sarpogrelate hydrochloride has strong selective platelet aggregation inhibiting effect and also has definite vasodilatation effect. In recent years, the research on the protection of vascular endothelium, the prevention of vascular smooth muscle proliferation, coronary heart disease and the like by the medicine is also paid attention to by clinicians. Chronic arterial occlusive disease can be clinically classified into atherosclerotic occlusive disease (ASo) and thromboangiitis obliterans (TAO), which have different pathogenesis, but are manifested as peripheral arterial occlusion. Various types of diabetes can cause macrovascular and microvascular disease, and the main pathological process of macrovascular complications is atherosclerosis. Atherosclerosis in diabetic patients occurs earlier, more widely and more severely than in non-diabetic patients. A large number of patients need treatment in China, and if the sarpogrelate hydrochloride made in China can be put on the market, the patients can select one more medicine, so that the impact on imported products can be caused, the selling price can be reduced, the treatment cost of the patients can be reduced, and the economic burden of the patients can be greatly reduced, so that good economic benefit and social benefit can be created after the sarpogrelate hydrochloride is put on the market.
At present, the dosage form on the market in China is a tablet, the original product is produced by Mitsubishi pharmaceutical company of Japan, the trade name is 'annelek', the product specification is 100mg, and the tablet has the characteristics of convenient taking, accurate dosage, reliable action and the like and can meet the requirements of chronic arterial occlusive disease.
According to the record of the drug specification of sarpogrelate hydrochloride of Mitsubishi corporation, the auxiliary materials used in the tablet are as follows:
cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, silicon dioxide, citric acid, magnesium stearate, hydroxypropyl methylcellulose, titanium dioxide, polyethylene glycol 6000 and talcum powder.
Disclosure of Invention
The invention aims to provide an oral solid pharmaceutical composition containing sarpogrelate hydrochloride, which consists of starch, lactose monohydrate, low-substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate lubricant, gastric-soluble film coating agent and citric acid, and is further prepared into a coated tablet by the following steps:
step one, taking sarpogrelate hydrochloride and citric acid, crushing, and respectively sieving with a 100-mesh sieve for later use;
step two, taking starch and lactose monohydrate, and sieving the starch and the lactose monohydrate by a 100-mesh sieve for later use;
step three, taking the hydroxypropyl methylcellulose and the low-substituted hydroxypropyl cellulose disintegrating agent, and respectively sieving the hydroxypropyl methylcellulose and the low-substituted hydroxypropyl cellulose disintegrating agent with a 80-mesh sieve for later use;
step four, dissolving the hydroxypropyl methylcellulose with the prescription amount into purified water to obtain 2.5% of water solution which is adhesive solution;
step five, taking the sarpogrelate hydrochloride, starch, lactose monohydrate, citric acid and low-substituted hydroxypropyl cellulose which are ground according to the prescription amount, uniformly mixing, preparing a soft material by using the adhesive solution obtained in the step four, granulating by using a 24-mesh sieve, drying, and finishing granules to obtain medicine-carrying dry granules;
taking the drug-loaded dry particles obtained in the step five, adding magnesium stearate, uniformly mixing, and tabletting to obtain sarpogrelate hydrochloride tablets;
and step seven, dispersing the gastric-soluble film coating agent in purified water, coating the sarpogrelate hydrochloride tablets obtained in the step six, and increasing the weight of the coating by 2.5% -3.5% to obtain the sarpogrelate hydrochloride coated tablets.
The gastric-soluble film coating agent is Opadry 03B2879, and the citric acid content is 2.8%.
The prescription and the preparation process of the sarpogrelate hydrochloride coated tablet are as follows:
prescription:
the above formula is prepared into film-coated tablets by the following steps:
a. weighing sarpogrelate hydrochloride and citric acid according to the prescription amount, crushing and sieving with a 100-mesh sieve, sieving lactose and starch with a 100-mesh sieve, sieving hydroxypropyl cellulose and hydroxypropyl methylcellulose with a 80-mesh sieve, and sieving magnesium stearate with a 60-mesh sieve for later use;
b. weighing hydroxypropyl methylcellulose with the prescription amount, and preparing into 2.5% solution with purified water as an adhesive for later use;
c. taking citric acid and hydroxypropyl cellulose in the prescription amount, multiplying and mixing with a proper amount of lactose monohydrate, and uniformly mixing with sarpogrelate hydrochloride, starch and the rest lactose monohydrate in the prescription amount for later use;
e. adding adhesive to prepare soft material. Granulating with 24 mesh sieve, drying at 60 + -5 deg.C until the drying weight loss is less than 3.5%, and grading with 30 mesh sieve;
f. calculating the yield of the dry particles, adding magnesium stearate according to the yield of the dry particles, and uniformly mixing for later use;
g. detecting and determining the weight of the tablet, and pressing the tablet core by using a shallow arc punch die (with a notch in the middle) with the diameter of 8.5 mm;
h. after the detection is qualified, coating a white film coat by Opadry 03B28796, wherein the solid content of the coating solution is 12%, and the weight is increased by 2.5-3.5%;
j. preparing a coating solution: purified water with 12% solid content and 3% weight gain. Weighing the coating powder, slowly adding into the pure water (the liquid level has just vortex) under stirring, stirring and dispersing uniformly, continuing stirring for 45min, and filtering with 80-mesh screen.
The technical scheme of the invention is further illustrated by the following experiments:
test one: and (3) testing compatibility of raw materials and auxiliary materials:
uniformly mixing starch, lactose, low-substituted-hydroxypropyl cellulose and main drug in a ratio of (5: 1) respectively; hydroxypropyl methylcellulose, magnesium stearate, citric acid, coating powder and main drug at a ratio of (1: 20) respectively, and mixing at illuminance of 4500Lx + -500 Lx, 40 deg.C and 60 deg.C in a thermostat with relative humidity of 75% (NaCl saturated solution) and relative humidity of 92.5% (KNO)3Saturated solution) was left for 10 days, and samples were taken at 5 and 10 days; taking starch, lactose, low-substituted-hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, citric acid and coating powder according to the formula, and uniformly mixing to prepare a blank total auxiliary material and main medicine in a ratio of 5: 1, mixing uniformly, standing for 10 days under the same condition, and sampling for 5 and 10 days; and placing sarpogrelate hydrochloride under the same condition, observing appearance, measuring related substances (calculated by an area normalization method), and comparing the result with the result of the raw material medicament for 0 day. The results are shown in tables 1 to 9.
TABLE 1 measurement results of related substances of sarpogrelate hydrochloride
TABLE 2 determination results of substances related to the compatibility of the total auxiliary materials with the main drugs
TABLE 3 measurement results of substances relating to the compatibility of lactose with the main drug
TABLE 4 measurement results of substances relating to the compatibility of starch with the principal drugs
TABLE 5 measurement results of substances relating to the compatibility of low-substituted hydroxypropylcellulose with the principal drug
TABLE 6 determination results of substances related to the compatibility of citric acid with the principal drugs
TABLE 7 measurement results of substances relating to the compatibility of hypromellose with the main drug
TABLE 8 evaluation results of substances relating to the compatibility of magnesium stearate with the principal drug
TABLE 9 measurement results of substances relating to the compatibility of the coating powder with the principal drug
Test results show that the total amount of hydrolysate and impurities of the raw material medicine of the product is not obviously changed and basically consistent when the raw material medicine is placed for 10 days under the conditions of 40 ℃, 60 ℃, RH 75%, RH 92.5%, 4500Lx +/-500 Lx and the results of 0 day are compared; after the auxiliary materials are mixed with the main medicine, the mixture is placed for 10 days under the conditions of RH 75%, RH 92.5% and 4500Lx +/-500 Lx, and the results of the mixture are compared with the results of 0 day, the total amount of impurities is not obviously changed and is basically consistent; after the total auxiliary materials and the main medicine are mixed, the known impurities are increased for 10 days at 40 ℃, the known impurities are obviously increased for 10 days at 60 ℃, but the impurities are still below the specified limit of 1.2 percent, which indicates that the selected auxiliary materials are compatible with the main medicine.
And (2) test II: prescription screening test:
the method is designed to coat, and the tablet core should have certain hardness and smaller friability requirement. Therefore, through screening, starch, lactose, hydroxypropyl methylcellulose, low-substituted-hydroxypropyl cellulose and the like with good compressibility, strong hydrophilicity and relatively low price are finally selected as main auxiliary materials, and citric acid and magnesium stearate. The adhesive adopts 2.5 percent hydroxypropyl methylcellulose aqueous solution, is convenient to use, has feasible process in large-scale production, and the prepared tablet has proper disintegration and meets the requirements of coating process on indexes such as hardness, friability and the like.
Table 10 prescription dose screening
Results of prescription screening
Table 11 prescription screening results
Prescription evaluation:
prescription 1: the use of purified water as a binder results in poor granulation and poor granule flowability.
Prescription 2: after the proportion of starch and lactose is adjusted based on the formula 1, the granulation effect and the granule fluidity are good. The surface of the sheet is smooth and has a cover falling phenomenon.
Prescription 3: on the basis of the formula 2, 2.5 percent of hydroxypropyl methylcellulose is used for replacing purified water for granulation instead of the adhesive, so that the granulation effect and the granule fluidity are good. The surface of the tablet is smooth and the molding is good. But dissolution was too slow, 68% in 15 minutes.
Prescription 4: on the basis of formula 3, low-substituted hydroxypropylcellulose is added to increase the compressibility, disintegration and dissolution rate of the tablet. The granulation effect and the granule fluidity are good. The sheet surface is smooth and clean, the forming is good, and the dissolution rate in 15 minutes is 96.28 percent. Based on the lab results, the prescription 4 is initially determined as the best prescription. 2000 tablets were prepared with formula 4 and process scale-up. The phenomenon of severe sticking occurs in the tabletting process.
Prescription 5: the granule has good fluidity, improves the sticking problem, but has relatively poor compressibility and cap falling phenomenon due to large addition amount of starch, and has the hardness of about 4-5 kg.
Prescription 6: based on the formula 5, the addition of starch is reduced, and the addition of hydroxypropyl cellulose is increased; the granule has good fluidity and compressibility, improved cap falling phenomenon, and hardness of about 6-7 kg. But the disintegration time is slower, about 15-17 minutes.
Prescription 7: continuously reducing the addition of starch and increasing the addition of hydroxypropyl cellulose based on the formula 6; the granule has good fluidity and compressibility, hardness of about 7-9kg, and disintegration time of about 9-12 min.
Comprehensively comparing the prescription 1 to the prescription 7, investigating the granulability, the granule fluidity, the repose angle, the tablet core appearance, the hardness, the friability, the disintegration time and the dissolution rate (15 minutes) in the preparation process of each prescription, and preliminarily determining the prescription 7 as the prescription of the product.
Based on the prescription screening and compatibility studies, prescription 7 was determined to be the preferred prescription and 50% proportionally reduced to a 50mg tablet prescription, as shown in table 12:
table 12 preferred recipe
Experiment three: comparison of the self-product with the related substances of the original research product
Original product:
trade name: annelike medicine
Specification: 100mg of
And (3) aluminum-plastic packaging: 9 pieces/plate
Production enterprises: mitsubishi Tanabe Pharma Corporation
Batch number: w016
The production date is as follows: 2014.03
Expiration date of 2017.02
Self-made sample
Sample name: sarpogrelate hydrochloride tablets
Specification: 50mg, 100mg
Double aluminum packaging: 9 pieces/plate
Production enterprises: self-made
TABLE 13 examination results of related substances of samples and original ground products
The results show that the three self-made samples have the known impurity of less than 1.2 percent, the single impurity of less than 0.1 percent and the total impurity of less than 1.5 percent, and are basically consistent with the impurity spectrum of the original product. But the total impurities were significantly lower than the commercial control.
Experiment four: comparison of dissolution behavior of self-product and original reference
Taking the product, and making into a dissolution determination method (XC second method, appendix of the second part of 2010 edition in Chinese pharmacopoeia). Respectively taking 0.1mol/L hydrochloric acid solution, pH4.0 acetate buffer solution, pH6.8 phosphate buffer solution and 900ml of water as dissolution media, rotating at 50 revolutions per minute, operating according to the method, taking 10ml of solution and filtering at specified time points (5min, 10min, 15min, 30min, 45min and 60min), precisely taking 5ml of subsequent filtrate, placing in a 10ml measuring flask, diluting to scale with hydrochloric acid solution, shaking uniformly to obtain a sample solution; precisely weighing 0.1g of sarpogrelate hydrochloride reference substance dried at 105 ℃ for 2 hours, placing the reference substance in a 100ml measuring flask, adding 10ml of methanol to dissolve the reference substance, diluting the reference substance to a scale with a hydrochloric acid solution, and shaking up; precisely measuring 5ml, placing in a 100ml measuring flask, diluting to scale with hydrochloric acid solution, and shaking to obtain reference solution. Taking the two solutions respectively, measuring absorbance at 272nm wavelength according to ultraviolet-visible spectrophotometry (appendix IVA of second part of Chinese pharmacopoeia 2010 edition), and calculating the dissolution amount of each tablet. The limit is 90% of the indicated amount and should be met. The results are as follows:
TABLE 14 comparison of dissolution data from the preparations to the original samples (%)
As can be seen from the data in the table above, the film coated tablet of sarpogrelate hydrochloride prepared according to the formulation and process described in this patent has similar dissolution behavior to the commercially available sarpogrelate hydrochloride tablet.
Test five self-made product and commercial product accelerated stability test result comparison
Taking 50mg and 100mg samples according to the market package, placing the samples in a constant temperature incubator with the temperature of 40 +/-2 ℃ and the relative humidity of 75 +/-5% for 6 months for test, respectively sampling in 1, 2, 3 and 6 months of the test, and inspecting according to the inspection items and the inspection method. The same method was also applied to the R679 batch of commercially available products.
TABLE 15 comparison of accelerated stability test results for self-made and commercial products
As can be seen from the data in the above table, the stability of the sarpogrelate hydrochloride film-coated tablet prepared according to the prescription and process of the present invention patent application is significantly improved on the basis of similar dissolution behavior with the commercially available product, which is particularly shown in that after 6 months of 2 specifications of the product at 40 ℃ +/-2 ℃ and 75% +/-5% relative humidity, the content of the product exceeds 98.5%, and the hydrolysate, other known impurities, the maximum unknown impurities, total impurities and content of the product do not exceed the standard limit, and the commercially available reference product is viewed reversely, so that the hydrolysate, total impurities and content of the product exceed the specified limit.
The detection proves that the sarpogrelate hydrochloride film-coated tablet has the characteristics of stable quality, simple production process, convenience in production and the like.
Detailed Description
The invention is further illustrated, but not limited, by the following specific examples.
EXAMPLE 50mg and 100mg preparation of film coated tablets of sarpogrelate hydrochloride
Prescription:
the above formula is prepared into film-coated tablets by the following steps:
a. weighing sarpogrelate hydrochloride and citric acid according to the prescription amount, crushing and sieving with a 100-mesh sieve, sieving lactose and starch with a 100-mesh sieve, sieving hydroxypropyl cellulose and hydroxypropyl methylcellulose with a 80-mesh sieve, and sieving magnesium stearate with a 60-mesh sieve for later use;
b. weighing hydroxypropyl methylcellulose with the prescription amount, and preparing into 2.5% solution with purified water as an adhesive for later use;
c. taking citric acid and hydroxypropyl cellulose in the prescription amount, multiplying and mixing with a proper amount of lactose monohydrate, and uniformly mixing with sarpogrelate hydrochloride, starch and the rest lactose monohydrate in the prescription amount for later use;
e. adding adhesive to prepare soft material. Granulating with 24 mesh sieve, drying at 60 + -5 deg.C until the drying weight loss is less than 3.5%, and grading with 30 mesh sieve;
f. calculating the yield of the dry particles, adding magnesium stearate according to the yield of the dry particles, and uniformly mixing for later use;
g. detecting and determining the weight of the tablet, and pressing the tablet core by using a shallow arc punch die (with a notch in the middle) with the diameter of 8.5 mm;
h. after the detection is qualified, coating a white film coat by Opadry 03B28796, wherein the solid content of the coating solution is 12%, and the weight is increased by 2.5-3.5%;
j. preparing a coating solution: purified water with 12% solid content and 3% weight gain. Weighing the coating powder, slowly adding into the pure water (the liquid level has just vortex) under stirring, stirring and dispersing uniformly, continuing stirring for 45min, and filtering with 80-mesh screen.
Claims (3)
1. An oral solid pharmaceutical composition containing sarpogrelate hydrochloride is characterized in that a unit preparation formula comprises the following components:
prescription:
further prepared into coated tablets by the following steps:
step one, taking sarpogrelate hydrochloride and citric acid, crushing, and respectively sieving with a 100-mesh sieve for later use;
step two, taking starch and lactose monohydrate, and sieving the starch and the lactose monohydrate by a 100-mesh sieve for later use;
step three, taking hydroxypropyl methylcellulose and low-substituted hydroxypropyl cellulose, and respectively sieving the hydroxypropyl methylcellulose and the low-substituted hydroxypropyl cellulose with a 80-mesh sieve for later use;
dissolving the hydroxypropyl methylcellulose with the prescription amount in purified water to obtain a 2.5% hydroxypropyl methylcellulose water solution serving as an adhesive;
step five, taking the sarpogrelate hydrochloride, starch, lactose monohydrate, citric acid and low-substituted hydroxypropyl cellulose which are ground according to the prescription amount, uniformly mixing, preparing a soft material by using the adhesive obtained in the step four, granulating by using a 24-mesh sieve, drying, and finishing granules to obtain medicine-carrying dry granules;
taking the drug-loaded dry particles obtained in the step five, adding magnesium stearate, uniformly mixing, and tabletting to obtain sarpogrelate hydrochloride tablets;
and seventhly, dispersing the coating agent Opadry 03B28796 in purified water, coating the sarpogrelate hydrochloride tablets obtained in the step six, and increasing the weight of the coating by 2.5-3.5% to obtain the sarpogrelate hydrochloride coated tablets.
2. An oral solid pharmaceutical composition containing sarpogrelate hydrochloride is characterized in that a unit preparation formula comprises the following components:
prescription:
further prepared into coated tablets by the following steps:
step one, taking sarpogrelate hydrochloride and citric acid, crushing, and respectively sieving with a 100-mesh sieve for later use;
step two, taking starch and lactose monohydrate, and sieving the starch and the lactose monohydrate by a 100-mesh sieve for later use;
step three, taking hydroxypropyl methylcellulose and low-substituted hydroxypropyl cellulose, and respectively sieving the hydroxypropyl methylcellulose and the low-substituted hydroxypropyl cellulose with a 80-mesh sieve for later use;
dissolving the hydroxypropyl methylcellulose with the prescription amount in purified water to obtain a 2.5% hydroxypropyl methylcellulose water solution serving as an adhesive;
step five, taking the sarpogrelate hydrochloride, starch, lactose monohydrate, citric acid and low-substituted hydroxypropyl cellulose which are ground according to the prescription amount, uniformly mixing, preparing a soft material by using the adhesive obtained in the step four, granulating by using a 24-mesh sieve, drying, and finishing granules to obtain medicine-carrying dry granules;
taking the drug-loaded dry particles obtained in the step five, adding magnesium stearate, uniformly mixing, and tabletting to obtain sarpogrelate hydrochloride tablets;
and seventhly, dispersing the coating agent Opadry 03B28796 in purified water, coating the sarpogrelate hydrochloride tablets obtained in the step six, and increasing the weight of the coating by 2.5-3.5% to obtain the sarpogrelate hydrochloride coated tablets.
3. An oral solid pharmaceutical composition of any one of claims 1-2 comprising sarpogrelate hydrochloride, prepared into a film coated tablet by the steps of:
a. weighing sarpogrelate hydrochloride and citric acid according to the prescription amount, crushing and sieving with a 100-mesh sieve, sieving lactose monohydrate and starch with a 100-mesh sieve, sieving low-substituted hydroxypropyl cellulose and hydroxypropyl methylcellulose with a 80-mesh sieve, and sieving magnesium stearate with a 60-mesh sieve for later use;
b. weighing hydroxypropyl methylcellulose with a prescription amount, and preparing a 2.5% hydroxypropyl methylcellulose water solution by using purified water as a binder solution for later use;
c. taking citric acid and low-substituted hydroxypropyl cellulose in the prescription amount, multiplying and mixing with a proper amount of lactose monohydrate, and uniformly mixing with sarpogrelate hydrochloride, starch and the rest lactose monohydrate in the prescription amount for later use;
e. adding adhesive to prepare soft material, granulating with 24 mesh sieve, drying at 60 + -5 deg.C until the drying weight loss is less than 3.5%, and grading with 30 mesh sieve;
f. calculating the yield of the dry particles, adding magnesium stearate according to the yield of the dry particles, and uniformly mixing for later use;
g. detecting and determining the weight of the tablet, and pressing the tablet core by using a shallow arc punch die with the diameter of 8.5mm and an indentation in the middle;
h. after the coating is qualified, coating a white film coating by Opadry 03B28796, wherein the solid content of the coating solution is 12 percent, and the weight of the coating is increased by 2.5-3.5 percent;
preparing a coating solution: weighing the coating powder, slowly adding into the stirred pure water, stirring and dispersing uniformly, continuously stirring for 45 minutes, and filtering by using a 80-mesh screen.
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