CN105434377B - Mei Suoshuli tablets and preparation method thereof - Google Patents

Mei Suoshuli tablets and preparation method thereof Download PDF

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Publication number
CN105434377B
CN105434377B CN201410438407.2A CN201410438407A CN105434377B CN 105434377 B CN105434377 B CN 105434377B CN 201410438407 A CN201410438407 A CN 201410438407A CN 105434377 B CN105434377 B CN 105434377B
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China
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weight
parts
mei suoshuli
crospovidone
pvp
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Expired - Fee Related
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CN201410438407.2A
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CN105434377A (en
Inventor
李莉娥
王学海
许勇
廖娟娟
黄怡
黄璐
涂荣华
杨仲文
乐洋
江曦
张绪文
何震宇
朱垒
余艳平
刘荃
王伟
田华
肖强
杨菁
张毅
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Hubei Co Ltd Of Bio-Pharmaceutical Industry Institute For Research And Technology
Ren Fu Pharmaceutical Group Stock Co
Wuhan Guanggu Humanwell Biological Pharmaceutical Co Ltd
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Hubei Co Ltd Of Bio-Pharmaceutical Industry Institute For Research And Technology
Ren Fu Pharmaceutical Group Stock Co
Wuhan Guanggu Humanwell Biological Pharmaceutical Co Ltd
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Application filed by Hubei Co Ltd Of Bio-Pharmaceutical Industry Institute For Research And Technology, Ren Fu Pharmaceutical Group Stock Co, Wuhan Guanggu Humanwell Biological Pharmaceutical Co Ltd filed Critical Hubei Co Ltd Of Bio-Pharmaceutical Industry Institute For Research And Technology
Priority to CN201410438407.2A priority Critical patent/CN105434377B/en
Priority to PCT/CN2014/085785 priority patent/WO2016029496A1/en
Publication of CN105434377A publication Critical patent/CN105434377A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A61J1/10—Bag-type containers
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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

Abstract

The present invention provides Mei Suoshuli tablets and preparation method thereof, the Mei Suoshuli tablets include：Mei Suoshuli and pharmaceutically acceptable auxiliary material.The Mei Suoshuli Dissolution of Tablet of the present invention is high, disintegration time is short, Small side effects, stable quality, and preparation process is simple, at low cost.

Description

Mei Suoshuli tablets and preparation method thereof
Technical field
The present invention relates to pharmaceutical fields, and in particular, to Mei Suoshuli tablets and preparation method thereof.
Background technology
Mei Suoshuli is the 1.1 class chemistry new drugs by Military Medical Science Institute and the cooperative development of people's good fortune Pharmaceutical Group.Mei Suo Shu Li is a kind of non-steroidal anti-inflammatory drugs (abbreviation NSAID), and main mechanism is inhibition cyclooxygenase (COX-2) activity, so as to Arachidonic acid is inhibited to ultimately generate prostacyclin (PG II), prostaglandin (PGE1, PGE2) and thromboxane A2 (TXA2), that is, is subtracted The synthesis of the inflammatory mediators such as few prostaglandin, thromboxane, thus there is good antipyretic, analgesia, anti-inflammatory, detumescence.It is beautiful Suo Shuli raw materials are not soluble in water, see report still without suitable Mei Suoshuli preparations at present.Thus, development efficacy is good, biological Availability is high, the Mei Suoshuli preparations of Small side effects, has very important significance.
However, the research to Mei Suoshuli preparations at present, still has to be strengthened.
Invention content
The present invention is directed to solve at least some of the technical problems in related technologies.For this purpose, the present invention One purpose is to propose that a kind of good effect, dissolution rate are high, bioavilability is high, stable quality Mei Suoshuli tablets.
In one aspect of the invention, the present invention provides a kind of Mei Suoshuli tablets.According to an embodiment of the invention, should Mei Suoshuli tablets include：Mei Suoshuli；And pharmaceutically acceptable auxiliary material.Inventor's discovery, Mei Suoshuli of the invention Dissolution of Tablet is high, disintegration time is short, Small side effects, stable quality, can effectively play anti-inflammatory, analgesia, it is antipyretic the effect of, and Preparation process is simple, at low cost, is suitble to industrialized production.
According to an embodiment of the invention, the pharmaceutically acceptable auxiliary material be selected from filler, disintegrant, adhesive and At least one of lubricant.
According to an embodiment of the invention, the filler is in lactose, cornstarch, microcrystalline cellulose, mannitol At least one, preferably lactose and microcrystalline cellulose combination.Thereby, it is possible to improve the compressibility of drug, main component is reduced Dose deviations, promote disintegration and dissolution.Particularly, inventor has found, when select the combination of microcrystalline cellulose and lactose as During filler, only drugs compressibility is not good, and disintegration rate is fast, and dissolution rate is high, and can improve the hardness of tablet and unilateral bright and clean Degree.
According to an embodiment of the invention, described adhesive is selected from PVP K30, hydroxypropyl methylcellulose, methylcellulose At least one, preferred PVP K30.Not only there is preferable adhesive effect as a result, and Mei Suoshuli tablets can be promoted Disintegration and dissolution.
According to an embodiment of the invention, the disintegrant is selected from crospovidone, sodium carboxymethyl starch, cross-linked carboxymethyl At least one of sodium cellulosate, preferably crospovidone.As a result, Mei Suoshuli tablets can fater disintegration, be conducive to Mei Suoshu The dissolution of profit.Particularly, inventor has found, when using crospovidone for disintegrant, the disintegration rate of Mei Suoshuli tablets Comparatively fast, dissolution rate is higher.
According to an embodiment of the invention, the lubricant is selected from magnesium stearate.The unilateral light of Mei Suoshuli tablets as a result, Cleanliness is good, and appearance meets the requirements.
According to an embodiment of the invention, according to parts by weight, the Mei Suoshuli tablets can include：The Mei Suoshuli 25-150 parts by weight, the filler 50-200 parts by weight, described adhesive 6-12 parts by weight, the disintegrant 5-20 weight Part, the lubricant 0.8-4 parts by weight.The disintegration rate of Mei Suoshuli tablets is fast as a result, dissolution rate is high, and bioavilability is high, And stable quality, toxic side effect are small.In addition, inventor is it was unexpectedly observed that the Mei Suoshuli tablets comprising aforementioned proportion supplementary material With the pharmaceutical properties better than other ratios.
A specific example according to the present invention, according to parts by weight, the Mei Suoshuli tablets include：Mei Suoshuli 50 Parts by weight, 50 parts by weight of lactose, 100 parts by weight of microcrystalline cellulose, 8 parts by weight of PVP K30,12 parts by weight of crospovidone, 2.5 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Mei Suoshuli tablets include：Mei Suoshuli 50 Parts by weight, 113 parts by weight of lactose, 57 parts by weight of microcrystalline cellulose, 8 parts by weight of PVP K30,12 parts by weight of crospovidone, 2.4 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Mei Suoshuli tablets include：Mei Suoshuli 50 Parts by weight, 135 parts by weight of lactose, 45 parts by weight of microcrystalline cellulose, 8 parts by weight of PVP K30,16 parts by weight of crospovidone, 2 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Mei Suoshuli tablets include：Mei Suoshuli 25 Parts by weight, 30 parts by weight of lactose, 120 parts by weight of microcrystalline cellulose, 6 parts by weight of PVP K30,6 parts by weight of crospovidone, 2 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Mei Suoshuli tablets include：Mei Suoshuli 25 Parts by weight, 200 parts by weight of cornstarch, 6 parts by weight of hydroxypropyl methylcellulose, 5 parts by weight of croscarmellose sodium, stearic acid 0.8 parts by weight of magnesium.
A specific example according to the present invention, according to parts by weight, the Mei Suoshuli tablets include：Mei Suoshuli 100 parts by weight, 40 parts by weight of lactose, 80 parts by weight of microcrystalline cellulose, 12 parts by weight of PVP K30,14 weight of crospovidone Part, 3 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Mei Suoshuli tablets include：Mei Suoshuli 100 parts by weight, 80 parts by weight of lactose, 40 parts by weight of microcrystalline cellulose, 7 parts by weight of PVP K30,12 weight of crospovidone Part, 2.5 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Mei Suoshuli tablets include：Mei Suoshuli 125 parts by weight, 50 parts by weight of mannitol, 10 parts by weight of methylcellulose, 14 parts by weight of crospovidone, 4 weight of magnesium stearate Part.
A specific example according to the present invention, according to parts by weight, the Mei Suoshuli tablets include：Mei Suoshuli 125 parts by weight, 60 parts by weight of lactose, 60 parts by weight of microcrystalline cellulose, 10 parts by weight of PVP K30,20 weight of sodium carboxymethyl starch Measure part, 3 parts by weight of magnesium stearate.
Inventor has found by a large amount of experiment, individually using lactose as filler when, industry, which produces greatly, will appear sliver and shows As so the present invention does not select lactose individually in the auxiliary material selection of diluent.But since the lactose as filler is water-soluble Property it is good, and microcrystalline cellulose not only serves as filler, and has the performance of disintegrant, chooses lactose and microcrystalline cellulose two Simultaneously as diluent (herein, " filler " and " diluent " may be used interchangeably), what be can reach is molten for the combination of person Go out effect.When the combination using lactose and microcrystalline cellulose is as filler, the dissolubility of Mei Suoshuli can be effectively improved, The combination of lactose and microcrystalline cellulose also is able to increase Mei Suoshuli tablet hardnesses and unilateral finish, accelerates Mei Suoshuli pieces The disintegration of agent, so as to improve the dissolution rate of Mei Suoshuli.According to an embodiment of the invention, the matter of lactose and microcrystalline cellulose is selected Amount is than being (0.25~3)：1, the most preferably optimum quality ratio of lactose and microcrystalline cellulose is 0.5：1.
In addition, according to an embodiment of the invention, use crospovidone that can further speed up Mei Suoshuli for disintegrant The disintegration rate of tablet improves the dissolution rate of Mei Suoshuli.
In another aspect of this invention, the present invention provides the methods for preparing foregoing Mei Suoshuli tablets.According to The embodiment of the present invention, this method include the following steps：Mei Suoshuli is subjected to micronization processes, and the Mei Suoshu that will be obtained Sharp micro powder granule and the mixing of pharmaceutically acceptable auxiliary material, to obtain the medicinal mixture；By the medicinal mixture into Mei Suoshuli labels to obtain Mei Suoshuli labels, are coated processing, to obtain Mei Suoshuli by row tabletting by described Tablet, wherein, the grain size of the Mei Suoshuli micro powder granules is 5-100 microns.Inventor has found, utilizes the party of the present invention Method can fast and effeciently prepare foregoing Mei Suoshuli tablets, and preparation process is simple, easy to operate, is easy to control System is suitble to industrialized production, while the Mei Suoshuli disintegration of tablet speed prepared is fast, and dissolution rate is high, and stable quality, Small side effects, can be effective for treatment inflammation, analgesia or analgesic.In the preceding processing of supplementary material, Mei Suoshuli and it will first fill out It fills after agent mixing is micronized, then Mei Suoshuli tablets obtained, relative to beautiful made from the Mei Suoshuli without micronizing Suo Shuli tablets, dissolution rate can significantly be improved.
According to an embodiment of the invention, the method for preparing Mei Suoshuli tablets may further include：Using polyvinyl chloride Bubble-cap+two-sided composite aluminium film bag packs the Mei Suoshuli tablets.Leakproofness is preferable as a result, can effectively prevent U.S. The Suo Shuli tablet moisture absorptions are conducive to the long-term storage of Mei Suoshuli tablets.
According to an embodiment of the invention, the method for preparing Mei Suoshuli tablets may comprise steps of：
(1) Mei Suoshuli and filler are mixed, and obtained mixture is subjected to micronization processes, to obtain grain Diameter is 5 microns to 100 microns of mixture micro powder granule, and disintegrant, adhesive and lubricant are smashed it through 80 mesh sieve respectively, It is spare；
(2) described adhesive is mixed with purified water, with obtained mass fraction be 6%~12% binder aqueous solution I, It is spare；
(3) the mixture micro powder granule with the disintegrant that Inner adds is mixed, obtains mixture II；
(4) described adhesive aqueous solution I is added in the mixture II, and softwood is made in obtained mixture, Gained softwood is crossed into 18 mesh stainless steel sieve series grains, to obtain wet granular；
(5) at 55 DEG C~65 DEG C, the wet granular is dried into 1~4h, 18 mesh stainless steels sieve whole grain is then crossed, to obtain Obtain dry particl；
(6) dry particl with additional disintegrant is mixed, then obtained mixture is mixed with magnesium stearate, with Just the medicinal mixture is obtained；
(7) content of dispersion of the medicinal mixture is measured, and is calculated the theoretical tablet weight, then carries out the medicinal mixture Tabletting, to obtain the Mei Suoshuli labels.
(8) coating powder is added in purified water, is configured to the Coating Solution that solid content is 20%, then utilizes the packet Clothing solution is coated processing to the Mei Suoshuli labels, to obtain the Mei Suoshuli tablets,
According to an embodiment of the invention, further comprise：
(9) the Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.
Thereby, it is possible to quickly and effectively prepare foregoing Mei Suoshuli tablets.Wherein, by by Mei Suoshuli Micronization processes are carried out, Mei Suoshuli is enabled to be dispersed in auxiliary material, effectively improves the dissolution rate of Mei Suoshuli.
The invention will be in two times added in disintegrant point plus disintegrant and additional disintegrant both forms, Additional disintegrant can promote the disintegration of particle, and interior plus disintegrant can then accelerate the dispersion of particle, can greatly improve Mei Suoshu The dissolution rate of sharp tablet.Result described in the embodiment of the present invention can be seen that the technique using addition inside and outside disintegrant, phase For disintegrant only with the technique of interior addition, dissolution rate significantly improves, and dissolution rate can be increased to more than 85%.Therefore it determines The dosage and addition manner of disintegrant be：The interior dosage of disintegrant is the 1/2 of disintegrant recipe quantity, and outer dosage is disintegrant prescription Another the 1/2 of amount.According to an embodiment of the invention, piece is controlled again during tabletting in the range of theoretical piece weight ± 5%, hardness control exists 5~7kg.The Mei Suoshuli tablet appearances that obtain as a result, piece meet the requirements, and disintegration rate is fast again etc., and dissolution rate is high.
According to an embodiment of the invention, the parameter of Cotton seeds can be：Average inlet air temperature is 85 DEG C, average piece bed temperature It is 41 DEG C, atomizing pressure 2.5bar to spend, and average coating pan rotating speed is 15~23rpm, 3~4g/min of average material flow.By This, Mei Suoshuli tablets it is unilateral bright and clean, appearance meets the requirements.
According to an embodiment of the invention, the gross mass based on the Mei Suoshuli labels, according to mass percent meter, coating Increase weight is 3.0~3.5%.The appearance requirement of Mei Suoshuli tablets can be met as a result, and influence collapsing for Mei Suoshuli tablets Solve time and dissolution rate, moreover it is possible to play preferable shaded effect.If coating weight gain is excessively high, during the disintegration of Mei Suoshuli tablets Between extend, dissolution rate declines, and if coating weight gain is too low, the appearance of Mei Suoshuli tablets is undesirable.
A specific example according to the present invention, the method for preparing Mei Suoshuli tablets include the following steps：
(1) Mei Suoshuli with lactose and microcrystalline cellulose is mixed, and obtained mixture is subjected to micronization processes, To obtain the mixture micro powder granule that grain size is 5 microns to 100 microns, by crospovidone, PVP K30 and tristearin Sour magnesium smashes it through 80 mesh sieve respectively, spare；
(2) PVP K30 is mixed with purified water, with the PVP K30 aqueous solution that obtained mass fraction is 6%~12% I, it is spare；
(3) the mixture micro powder granule with the crospovidone that Inner adds is mixed, obtains the mixture II；
(4) the PVP K30 aqueous solution I is added in the mixture II, and obtained mixture is made soft Gained softwood is crossed 18 mesh stainless steel sieve series grains, obtains the wet granular by material；
(5) at 55 DEG C~65 DEG C, the wet granular is dried into 1~4h, 18 mesh stainless steels sieve whole grain is then crossed, to obtain Obtain the dry particl；
(6) dry particl with additional crospovidone is mixed, and obtained mixture is mixed with magnesium stearate It closes, to obtain the medicinal mixture；
(7) content of dispersion of the medicinal mixture is measured, and is calculated the theoretical tablet weight, based on the theoretical piece weight, by described in Medicinal mixture carries out tabletting, to obtain the Mei Suoshuli labels；
(8) coating powder white stomach dissolution type Opadry 81W68907 is added in purified water, being configured to solid content is 20% Coating Solution, with screw type stirring paddle stirring 45 minutes, then using common transformation coating pan to label into The row Cotton seeds, to obtain the Mei Suoshuli tablets,
Wherein, the parameter of the Cotton seeds is as follows：Average inlet air temperature is 85 DEG C, and average piece bed tempertaure is 41 DEG C, mist Change pressure is 2.5bar, and average coating pan rotating speed is 15~23rpm, averagely 3~4g/min of material flow,
Coating weight gain 3%~3.5%,
(9) the Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.
Thereby, it is possible to fast and effeciently prepare foregoing Mei Suoshuli tablets, preparation process is simple, operation side Just, and the Mei Suoshuli tablet qualities that prepare are stablized, and disintegration rate is fast, and dissolution rate is high.
In particular, it should be pointed out that Mei Suoshuli and lactose are micronized, the Mei Suoshuli of slightly solubility is enabled to It is adequately dispersed in hydrophilic lactose, is then mixed again with other auxiliary materials, in this way manufactured Mei Suoshuli pieces Agent, dissolution rate can significantly be improved.In addition, crospovidone is arrived by adding (addition and outer addition in i.e.) twice In medicinal mixture, additional disintegrant can promote the disintegration of particle, and interior plus disintegrant can then accelerate the dispersion of particle, the method It can achieve the effect that preferably to dissolve out using less disintegrant holding, not only can be cost-effective, while can accelerate The disintegration and dispersion of grain are conducive to improve dissolution rate.
By the preparation-obtained Mei Suoshuli pieces (Film coated tablets) of the present invention, character, hardness, friability, tablet weight variation It meets the requirements, and dissolution rate is higher, and can reach 90%, meet the requirements.
According to an embodiment of the invention, 10 days influence factor result of the tests of Mei Suoshuli tablets show：Mei Suoshuli pieces Agent is placed 10 days under high temperature, high humidity, illumination, and content, related substance change without conspicuousness, and quality is basicly stable, shows prescription Science is feasible, rational technology, favorable reproducibility.But 10 days tablet surfaces of high humidity have the slight moisture absorption, and dissolution rate is declined, and prompt choosing It is noted that moisture-proof when selecting packaging.Therefore, product needs to store at hermetically drying.
Further, according to an embodiment of the invention, the interior packaging material of Mei Suoshuli tablets of the present invention is selected, The Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.Leakproofness is preferable as a result, energy The Mei Suoshuli tablet moisture absorptions are enough effectively prevent, the long-time stability of this product can be effectively ensured, are conducive to the length of Mei Suoshuli tablets Phase stores.According to an embodiment of the invention, the invention has the advantages that：
1st, according to an embodiment of the invention, by using the combination of microcrystalline cellulose and lactose as filler, not only medicine Object compressibility is good, and disintegration rate is fast, and dissolution rate is high, and can improve the hardness of tablet and unilateral finish, accelerates Mei Suoshuli The disintegration of tablet, so as to improve the dissolution rate of Mei Suoshuli, and lactose hydrophily is preferable, can further be effectively improved Mei Suoshu The dissolubility of profit.
2nd, according to an embodiment of the invention, in the preceding processing of supplementary material, first Mei Suoshuli and filler is mixed and carried out After micronizing, the Mei Suoshuli of slightly solubility is enabled to adequately to be dispersed in hydrophilic filler such as lactose, then again with Other auxiliary materials mix, and manufactured Mei Suoshuli tablets, dissolution rate can significantly be improved in this way.
3rd, according to an embodiment of the invention, disintegrant is added by inside and outside addition, can not only reduces the use of disintegrant Amount, it is cost-effective, meanwhile, additional disintegrant can promote the disintegration of Mei Suoshuli tablets, and interior plus disintegrant can promote to be disintegrated The dispersion of particle can significantly improve the result of extraction of Mei Suoshuli tablets.
4th, according to an embodiment of the invention, piece is controlled again during tabletting in the range of theoretical piece weight ± 5%, hardness control exists 5~7kg.The Mei Suoshuli tablet appearances that obtain as a result, piece meet the requirements, and disintegration rate is fast again etc., and dissolution rate is high.
5th, according to an embodiment of the invention, control coating weight gain is the 3.0~3.5% of Mei Suoshuli label quality, can Meet the appearance requirement of Mei Suoshuli tablets, and do not influence the disintegration time and dissolution rate of Mei Suoshuli tablets, moreover it is possible to play compared with Good shaded effect.
6th, using this method of the present invention, foregoing Mei Suoshuli tablets can be fast and effeciently prepared, are made It is standby simple for process, it is easy to operate, it is easily controllable, it is suitble to industrialized production, while the Mei Suoshuli disintegration of tablet prepared Speed is fast, and dissolution rate is high, and stable quality, Small side effects, can be effective for treatment inflammation, analgesia or analgesic.
Specific embodiment
The embodiment of the present invention is described below in detail.The embodiments described below is exemplary, and is only used for explaining this hair It is bright, and be not considered as limiting the invention.Particular technique or condition are not specified in embodiment, according to text in the art It offers described technology or condition or is carried out according to product description.Reagents or instruments used without specified manufacturer is removed Mei Suoshuli raw materials are outer for self-control, and other auxiliary materials are can be with conventional products that are commercially available.
Embodiment 1：Main ingredient is tested with auxiliary material interaction
In the present embodiment, whether there are interaction and preparation in main ingredient and prescription between selected auxiliary material to investigate Whether crystal form has change in the process, using liquid chromatography (according to Chinese invention patent application 201310476323.3 (CN103553984A) Mei Suoshuli HPLC detection methods disclosed in embodiment 8) it is mutual between selected auxiliary material and main ingredient Effect is studied.
Specifically, by independent auxiliary material, the mixture of main ingredient and each independent auxiliary material, the mixture of main ingredient and all auxiliary materials It is placed 10 days under the conditions of influence factor respectively, after comparing 0 day and 10 days, the character of mixture, the change in relation to substance and content Change.
1st, the preparation of test sample
The lot number of bulk pharmaceutical chemicals (Mei Suoshuli)：101217 batches (Ren Fu Pharmaceutical Groups joint-stock company makes by oneself, purity 99.8%), Mei Suoshuli bulk pharmaceutical chemicals are first crossed into 60 mesh sieve, each auxiliary material crosses 80 mesh sieve.
No. 1 sample：Main ingredient and microcrystalline cellulose (mass ratio 1:5) mixture；
0.1g Mei Suoshuli bulk pharmaceutical chemicals and 0.5g microcrystalline celluloses are weighed, cross 60 mesh sieve mixing 3 times, number is 1.
No. 2 samples：Main ingredient and lactose (mass ratio 1:5) mixture；
0.1g Mei Suoshuli bulk pharmaceutical chemicals and 0.5g lactose are weighed, cross 60 mesh sieve mixing 3 times, number is 2.
No. 3 samples：Main ingredient and PVP K30 (mass ratio 5:1) mixture
0.5g Mei Suoshuli bulk pharmaceutical chemicals and 0.1g PVP K30s are weighed, cross 60 mesh sieve mixing 3 times, number is 3.
No. 4 samples：Main ingredient and crospovidone (mass ratio 5:2) mixture
0.5g Mei Suoshuli bulk pharmaceutical chemicals and 0.2g crospovidone are weighed, cross 60 mesh sieve mixing 3 times, number is 4.
No. 5 samples：Main ingredient and magnesium stearate (mass ratio 20:1) mixture
2g Mei Suoshuli bulk pharmaceutical chemicals and 0.1g magnesium stearates are weighed, cross 60 mesh sieve mixing 3 times, number is 5.
No. 6 samples：Main ingredient and mixed accessories (mass ratio 1:5) mixture；
Weigh 0.1g Mei Suoshuli bulk pharmaceutical chemicals and 0.5g mixtures (wherein lactose 0.23g+ microcrystalline celluloses 0.23g+ Crospovidone 0.04g), 60 mesh sieve mixing 3 times are crossed, number is 6.
2nd, test method
Above-mentioned 1-6 samples are respectively placed in high temperature, high humidity and lower 10 days of illumination condition, after comparing 0 day and 10 days, mixing The character of object, the variation in relation to substance and content, result of the test are shown in Table 1.
Wherein, impurity 1 is compound, structure shown in the formula I disclosed in Chinese invention patent application CN103553984A Formula is as follows：
1 main ingredient of table and auxiliary material compatibility experiments result
3rd, conclusion
1~No. 6 sample placed 10 days under high temperature, high humidity and illumination condition after measurement result, compared with 0 day, property Shape, content do not have significant change, and impurity 1 does not have increase trend, and without generating new impurity, the results showed that, each auxiliary material and master Compatibility is good between medicine, does not interact between Mei Suoshuli and each auxiliary material.
Embodiment 2：The formulation study of Mei Suoshuli pieces
Since main ingredient Mei Suoshuli is practically insoluble in water, and main ingredient amount is also larger, therefore, the difficult point of formulation and technology is to carry The dissolution rate of high this product.In the present embodiment, prescription of the specification for the Mei Suoshuli tablets of 50mg/ pieces is studied, is had For body, due to Mei Suoshuli raw materials aqueous solubility and mobility inequality, consider to add in water soluble adjuvant and disintegrant promotion is molten Go out, devise 9 prescriptions, be shown in Table 2.
The different Formulation of table 2
Note：In the preparation of adhesive, hydroxypropyl methylcellulose need to add purified water be configured to 4% hydroxypropyl methylcellulose it is water-soluble Liquid (g/g), PVP K30 need to add purified water be configured to 8% PVP K30 aqueous solution (g/g).
By the prescriptions in table 1, using wet granulation technology, Mei Suoshuli labels are first prepared, measure dissolution rate,
Preparation method is specific as follows：
(1) supplementary material pre-treatment：After main ingredient (Mei Suoshuli), each auxiliary material are crushed respectively, main ingredient crosses 60 mesh sieve, auxiliary material mistake 80 mesh sieve, spare；
(2) with adhesive：
When the adhesive in prescription selects PVP K30 (PVPK30), 8 grams of PVP K30s are weighed in beaker, are added pure Change 92 grams of water, stir to clarify, obtain 8% PVP K30 aqueous solution I, it is spare；
When the adhesive in prescription selects hydroxypropyl methylcellulose, 4 grams of hydroxypropyl methylcelluloses are weighed in beaker, add purifying 96 grams of water, stirs to clarify, and obtains 4% hydroxypropyl methylcellulose aqueous solution I, spare；
(3) it mixes：It weighs the main ingredient of recipe quantity, filler after mixing, adds disintegrant crospovidone (PVPP) it is uniformly mixed, obtains mixture II；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into about 2h at 60 DEG C ± 5 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：Recipe quantity magnesium stearate is added in dry particl, is uniformly mixed, obtains and always mixes particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, control pressure make tablet hardness within 5~7kg, and tabletting to obtain the final product.
Dissolution determination：
By the assay method under 2010 editions dissolution rate items of Chinese Pharmacopoeia, above-mentioned 9 prescriptions are measured 45 points in dissolution medium (sodium hydroxide 2.30g, potassium dihydrogen phosphate 7.65g add water to make molten for phosphate buffer for the dissolution rate of clock, wherein dissolution medium It solves as 1000ml, with phosphoric acid tune pH to 8.8), dissolution determination the results are shown in Table 3.
The dissolution rate comparison of 3 each tablet formulation of table
Prescription 1 2 3 4 5 6 7 8 9
Dissolution rate (%) 81.3 71.6 70.9 80.2 72.3 71.1 72.8 80.6 71.9
In terms of dissolution result, designed 9 prescription dissolution rates of 45 minutes in dissolution medium are shown, preferably prescription For prescription 1, prescription 4, prescription 8.Due to Mei Suoshuli poorly water-solubles, and hypromellose is known as the molten effect of resistance, may be in sample Product influence dissolution rate during keeping sample, it is longer the time required to complete swelling in water in addition, is unfavorable for industrialized production, therefore not It is preferred that it is as adhesive.But due to previous experiments research shows that：When individually using lactose as filler, the big production of industry will appear Sliver phenomenon, so the present invention does not select lactose individually in the auxiliary material selection of diluent.But due to the breast as filler Sugared good water solubility, and microcrystalline cellulose not only serves as filler, and has the performance of disintegrant, chooses lactose and crystallite is fine The plain combination of dimension as diluent (herein, " filler " and " diluent " may be used interchangeably), can reach simultaneously Good result of extraction.
Therefore originally determine based on prescription 1, further investigate the screening optimal proportion of filler and dosage, adhesive Concentration and improve disintegrant addition manner, prescription and preparation process are advanced optimized.
Embodiment 3：The Mei Suoshuli tablet recipes and process optimization of 50mg specifications
This research is promulgated according to 2010 editions dosage form requirements to tablet of Chinese Pharmacopoeia with reference to CDE《Chemicals medicine is ground Study carefully basic fundamental guideline》, with reference to the characteristics of tablet, with character, hardness, friability, disintegration time, dissolution rate etc. to investigate Index, the type and dosage for using this product prescription auxiliary material are further screened.
(1) screening of diluent
In example 2 on the basis of prescription 1, the ratio and dosage of lactose and microcrystalline cellulose are adjusted, investigates diluent The influence of different proportion and dosage to tabletting formability and dissolution rate, it is specific as follows：
According to prescription shown in table 4 and the preparation method described in embodiment 2, pelletized, pressed with the batch of 1000/batches Then piece measures the hardness of Mei Suoshuli tablets, friability, disintegration time and the dissolution rate prepared, screen filler.Knot Fruit is shown in Table 4.
Wherein in prescription 10- prescriptions 14, the preparation method of adhesive is：8 grams of PVP K30s are weighed in beaker, are added pure Change 92 grams of water, stir to clarify, obtain 8% PVP K30 aqueous solution.
The screening prescription and measurement result of 4 filler of table
It can be seen from the result of table 4 in above-mentioned 5 prescriptions, since lactose proportion is larger, crystallite is fine in prescription 12 The plain proportion of dimension is smaller, causes disintegrating property slightly worse, dissolution rate is slightly lower, and disintegration and the dissolution rate of prescription 10,11,13,14 Preferably, dissolution rate can reach more than 80%, therefore select the mass ratio of lactose and microcrystalline cellulose as (0.25~3)：1, The dissolution rate of wherein 10 gained of prescription is best and disintegration time is moderate, therefore it is preferred that the optimum quality ratio of lactose and microcrystalline cellulose It is 0.5：1.
(2) selection of binder dosage
PVP K30 is chosen as adhesive, and the aqueous solution for preparing various concentration compares its bonding effect Research, investigates influence of the dosage of adhesive to Mei Suoshuli tablets, specific as follows：
According to the prescription shown in table 5 and the preparation method in embodiment 2, Mei Suoshuli tablets are prepared, were prepared The situation of Mei Suoshuli softwoods and particle is observed in journey, and measures the hardness of Mei Suoshuli tablets prepared, friability, collapse Solution time and dissolution rate, prescription and measurement result are shown in Table 5,
Wherein, prescription shown in table 5 is the supplementary material dosage for preparing 1000 tablets of Mei Suoshuli tablets.
Wherein, in prescription 15, the preparation method of adhesive is：4 grams of PVP K30s are weighed in beaker, add purified water It 96 grams, stirs to clarify, obtains 4% PVP K30 aqueous solution；Wherein in prescription 16, the preparation method of adhesive is：Weigh 8 grams PVP K30 adds 92 grams of purified water, stirs to clarify in beaker, obtains 8% PVP K30 aqueous solution；Wherein in prescription 17, The preparation method of adhesive is：12 grams of PVP K30s are weighed in beaker, adds 88 grams of purified water, stirs to clarify, it is poly- to obtain 12% Tie up ketone K30 aqueous solutions；Wherein in prescription 18, the preparation method of adhesive is：6 grams of PVP K30s are weighed in beaker, add purifying 94 grams of water, stirs to clarify, and obtains 6% PVP K30 aqueous solution；Wherein in prescription 19, the preparation method of adhesive is：Weigh 15 Gram PVP K30 adds 85 grams of purified water, stirs to clarify, obtain 15% PVP K30 aqueous solution in beaker.
The prescription screening of 5 binder dosage of table
From the results shown in Table 5, in prescription 15, when binder concn is 4%, softwood is done, and is easily sieved, particle Small, fine powder is more, tablet toughness can be caused insufficient, and the tablet content uniformity obtained during tabletting is unqualified；In prescription 18 when When binder dosage reaches 15%, obtained softwood is wetter, it is more difficult to be sieved, particle has strip, consolidation, and when extending disintegration Between；The raising of binder dosage is to dissolution, mobility of particle without too big improvement result.And in prescription 16, prescription 17, when viscous When a concentration of 6g (6%), the 8g (8%) or 10g (10%) of mixture, obtained softwood dry and wet degree is moderate, is easily sieved and obtains The particle rounding arrived, uniformly, good fluidity is easy to carry out tabletting.Therefore the dosage of determining adhesive is 6~12g/1000 pieces.
(3) screening of disintegrant dosage
In the present embodiment, the shadow of the dosage of disintegrant and the addition manner of disintegrant to Mei Suoshuli tablets has been investigated It rings, it is specific as follows：
According to the formula shown in table 6 and the preparation method in embodiment 2, Mei Suoshuli pieces are prepared.
It should be noted that in the present embodiment, the addition manner of disintegrant is two kinds：Interior addition and outer addition.
Interior addition is that disintegrant is added in mixing step, and outer addition refers to always mix in step, before lubricant is added in, First dry particl and disintegrant are uniformly mixed.
Inside and outside disintegrant progress during addition, by the prescription in table 6, using wet granulation technology, Mei Suoshu is prepared respectively Sharp tablet, preparation method are as follows：
(1) supplementary material pre-treatment：After main ingredient (Mei Suoshuli), each auxiliary material are crushed respectively, main ingredient crosses 60 mesh sieve, auxiliary material mistake 80 mesh sieve, spare；
(2) with adhesive：10 grams of PVP K30s are weighed in beaker, adds 90 grams of purified water, stirs to clarify, obtain 10% PVP K30 aqueous solution I, it is spare；
(3) it mixes：Weigh the main ingredient of recipe quantity, recipe quantity filler after mixing, add the disintegration that Inner is needed to add Agent crospovidone is uniformly mixed, and obtains mixture II；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into about 2h at 60 DEG C ± 5 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：The additional disintegrant crospovidone of the need of recipe quantity is added in dry particl, adds recipe quantity tristearin Sour magnesium is uniformly mixed, and is obtained and is always mixed particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, control pressure make tablet hardness within 5~7kg, and tabletting to obtain the final product.
Then the hardness of Mei Suoshuli tablets, friability, disintegration time and the dissolution rate prepared, measurement result are measured It is shown in Table 6.Wherein, recipe quantity of the formula of prescription 20- prescriptions shown in table 6 24 to prepare 1000 Mei Suoshuli pieces.
The prescription screening of 6 disintegrant of table
Note："-" expression does not contain respective components
From the results shown in Table 6, prescription 20, prescription 21 and 22 dissolution results difference of prescription are little, illustrate to reduce A certain amount of disintegrant can still keep preferably dissolving out, while can be with cost-effective.The disintegrant of prescription 23 and prescription 24 Using inside and outside addition, dissolution rate significantly improves.Additional disintegrant can promote the disintegration of particle, and interior plus disintegrant can then be accelerated The dispersion of particle is conducive to improve dissolution rate.It can be seen from the results above that using the technique of addition inside and outside disintegrant, relatively In disintegrant only with the technique of interior addition, dissolution rate significantly improves, and dissolution rate can be increased to more than 85%.Therefore it determines to collapse Solve agent dosage and addition manner be：The interior dosage of disintegrant is the 1/2 of disintegrant recipe quantity, and outer dosage is disintegrant recipe quantity Another 1/2.Therefore, it is prescription 24 to fix tentatively prescription.
Embodiment 4：Preparation process advanced optimizes experiment
1st, Mei Suoshuli bulk pharmaceutical chemicals grain size is investigated
Influence of the grain size of Mei Suoshuli bulk pharmaceutical chemicals to Mei Suoshuli pieces is investigated in accordance with the following steps, it is specific as follows：
Based on the prescription 24 in embodiment 3, the preparation process of the present invention is advanced optimized, to further improve The dissolution rate of Mei Suoshuli pieces of the present invention.
Specifically, according to prescription 24, two groups of (A groups and B groups) Mei Suoshuli tablets are prepared respectively, prepare A groups Mei Suoshuli The method of tablet is as described below, and the preparation method of B group Mei Suoshuli tablets exists with the preparation method difference of A group Mei Suoshuli tablets In the mixture of main ingredient Mei Suoshuli and auxiliary material filler does not carry out micronization processes.It is specific as follows：
The preparation method of A group Mei Suoshuli tablets is as follows：
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and auxiliary material filler are mixed and are micronized that (grain size is micro- 5 Rice to 100 microns), remaining each auxiliary material smash it through respectively 80 mesh sieve, it is spare；
(2) with adhesive：8 grams of PVP K30s are weighed in beaker, adds 92 grams of purified water, stirs to clarify, it is poly- to obtain 8% Ketone K30 aqueous solutions I are tieed up, it is spare；
(3) it mixes：By Mei Suoshuli and filler after mixing, the disintegrant crospovidone mixing that Inner is needed to add is added in Uniformly, mixture II is obtained；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into about 2h at 60 DEG C ± 5 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：The additional disintegrant crospovidone of the need of recipe quantity is added in dry particl, adds recipe quantity tristearin Sour magnesium is uniformly mixed, and is obtained and is always mixed particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, control pressure make tablet hardness within 5~7kg, and tabletting to obtain the final product.
Then the dissolution rate of two groups of Mei Suoshuli tablets prepared is measured, measurement result is shown in Table 7.
Table 7
As shown in Table 7, relative to the Mei Suoshuli without micronizing, first by Mei Suoshuli and filler lactose, And microcrystalline cellulose mixing is micronized, then the dissolution rate of Mei Suoshuli tablets obtained can significantly be improved.
2nd, tablet forming technique is investigated
According to working condition, bonding pad weight and thick suitable for piece, while to consider to meet friability requirement, using tablet press machine into Row tabletting.By the hardness level control of tablet in section shown in table 8, the then friability of the tablet of measure different hardness, dissolution Degree and disintegration time, measurement result are shown in Table 8.
Table 8 investigates influence of the hardness to experimental result
As can be known from the results of Table 8：When range of the hardness of tablet between 4~7kg, disintegration time and dissolution rate are by it It influences little；And when hardness is in 7~8kg, dissolution rate reduces；And when hardness is in 4~5kg, friability is big；In view of tablet It also needs to be coated, to the more demanding of friability, therefore, it is comparatively ideal range that the hardness of tablet, which is controlled in 5~7kg,.
Wherein, prescription 24 is the Mei Suoshuli pieces that specification is 50mg, and prescription is：Mei Suoshuli 50g, lactose 50g, crystallite Cellulose 100g, PVP K30 8g, crospovidone (interior to add) 6g, crospovidone (additional) 6g, magnesium stearate 2.5g.
Prescription 25 is the Mei Suoshuli pieces that specification is 100mg, and prescription is：Mei Suoshuli 100g, lactose 40g, crystallite are fine Tie up element 80g, PVP K30 8g, crospovidone (interior to add) 6g, crospovidone (additional) 6g, magnesium stearate 2.5g.
Preparation method is as follows：
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and auxiliary material filler are mixed and are micronized that (grain size is micro- 5 Rice to 100 microns), remaining each auxiliary material smash it through respectively 80 mesh sieve, it is spare；
(2) with adhesive：8 grams of PVP K30s are weighed in beaker, adds 92 grams of purified water, stirs to clarify, it is poly- to obtain 8% Ketone K30 aqueous solutions I are tieed up, it is spare；
(3) it mixes：By Mei Suoshuli and filler after mixing, the disintegrant crospovidone mixing that Inner is needed to add is added in Uniformly, mixture II is obtained；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into about 2h at 60 DEG C ± 5 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：The additional disintegrant crospovidone of the need of recipe quantity is added in dry particl, adds recipe quantity tristearin Sour magnesium is uniformly mixed, and is obtained and is always mixed particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, respectively control pressure tablet hardness is made to carry out tabletting within 4~5kg, 5~6kg, 6~7kg, 7~8kg up to above-mentioned The Mei Suoshuli pieces of different hardness.
3rd, art for coating is studied
In order to ensure tablet quality and conveniently take, often in Mei Suoshuli labels, (label herein refers to above-mentioned implementation The Mei Suoshuli tablets not being coated in example) the suitable clothing layer material of surface layer package, the drug in tablet is made to be isolated from the outside, Obtain in tablet of the Mei Suoshuli medical surfaces covered with film-coating, so as to reach moisture-proof, be protected from light, completely cut off air oxidation, enhancing The stability that drug preserves covers the bad odor in tablet and reduces the purpose of medicine irritation.
(1) coating material is：White stomach dissolution type Opadry 81W68907, Shanghai Colorcon Coating Technology Co., Ltd's life Production.
(2) coating solution is prepared
Coating powder is added in purified water, the solution of solid content 20% is configured to, with screw type stirring paddle stirring 45 minutes.The coating solution made can directly pump out use by peristaltic pump from liquid dispensing container.
(3) coating conditions
85 DEG C of inlet air temperature is set, average piece bed tempertaure is 41 DEG C, coating pan 15~23r/min of rotating speed, spouting velocity 3~ 4g/min.After every weightening to setting value, stop spray coating solution, drying of blowing a cold wind over treats that piece temperature is cooled to room temperature slice, uses film It is packed good, it weighs, takes a sample to check.
(4) screening of coating powder dosage
When taking according to the prescription of prescription 25 and technique, particularly tabletting, control pressure makes tablet hardness within 5~7kg The obtained Mei Suoshuli piece samples of tabletting are carried out, by the 5% of label weight, weigh coating powder, add purified water that solid content is made to be 20% solution, investigates the coating effect of different coating weight gains, and investigation the results are shown in Table 9.
The screening of 9 coating powder dosage of table
Coating weight gain Coating effect (amplification sem observation) Disintegration time (s)
1.8% Package is complete, but edge is imperfect substantially for label 80
3.0% Coating tablet is fully wrapped around, and color is uniform, and edge is complete 101
3.5% Coating tablet is fully wrapped around, and color is uniform, and edge is complete 112
4.0% Coating tablet is fully wrapped around, and color is uniform, and edge is complete 166
Table 9 the result shows that, coating powder dosage be label weight more than 3.0% when, coating tablet appearance can meet will It asks, and as coating powder dosage increases, disintegration time accordingly extends, when coating powder dosage is 4.0%, disintegration time, which exists, to be added The extended possibility of speed.It is as shown in table 10 below that basic performance evaluation is carried out to the coating tablet that above-mentioned three kinds of appearances are met the requirements：
10 coating tablet basic performance of table is evaluated
Consider with reference to the result of table 9 and table 10, control coating weight gain in label weight when selection is coated 3.0%-3.5% can meet the appearance requirement of coating tablet and influence disintegration time and dissolution rate, moreover it is possible to play preferable Shaded effect.
Embodiment 5：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 50g, lactose 50g, microcrystalline cellulose 100g, PVP K30 8g, crospovidone (interior to add) 6g are handed over Connection povidone (additional) 6g, magnesium stearate 2.5g is made 1000 altogether.
Preparation method：
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and auxiliary material filler lactose, microcrystalline cellulose mixing are carried out micro- Dusting (grain size is at 5 microns to 100 microns), remaining each auxiliary material smash it through 80 mesh sieve respectively, spare；
(2) with adhesive：8 grams of adhesive PVP K30s are weighed in beaker, adds 92 grams of purified water, stirs to clarify, obtain The binder aqueous solution I of 8% PVP K30, it is spare；
(3) it mixes：By Mei Suoshuli and filler after mixing, the disintegrant crospovidone mixing that Inner is needed to add is added in Uniformly, mixture II is obtained；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into 2h at 60 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：The additional disintegrant crospovidone of the need of recipe quantity is added in dry particl, adds recipe quantity tristearin Sour magnesium is uniformly mixed, and is obtained and is always mixed particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, control pressure make tablet hardness within 5~7kg, and tabletting to obtain the final product.
(9) it is coated：Coating powder white stomach dissolution type Opadry 81W68907 is added in purified water, is configured to solid content For 20% Coating Solution, paddle stirring is stirred 45 minutes with screw type.Label is carried out using common transformation coating pan Coating, get Mei Suoshuli Film coated tablets.Wherein, the major parameter of coating process is as follows：Average inlet air temperature is 85 DEG C, average piece Bed tempertaure is 41 DEG C, atomizing pressure 2.5bar, and average coating pan rotating speed is 15~23rpm, 3~4g/ of average material flow Min, weightening 3%~3.5%, obtains the Mei Suoshuli tablets.
(10) it packs：The Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.
Embodiment 6：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 50g, lactose 113g, microcrystalline cellulose 57g, PVP K30 8g, crospovidone (interior to add) 6g are handed over Connection povidone (additional) 6g, magnesium stearate 2.4g is made 1000 altogether.
Preparation method：
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and auxiliary material filler lactose, microcrystalline cellulose mixing are carried out micro- Dusting (grain size is at 5 microns to 100 microns), remaining each auxiliary material smash it through 80 mesh sieve respectively, spare；
(2) with adhesive：8 grams of adhesive PVP K30s are weighed in beaker, adds 92 grams of purified water, stirs to clarify, obtain The binder aqueous solution I of 8% PVP K30, it is spare；
(3) it mixes：By Mei Suoshuli and filler after mixing, the disintegrant crospovidone mixing that Inner is needed to add is added in Uniformly, mixture II is obtained；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into 4h at 55 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：The additional disintegrant crospovidone of the need of recipe quantity is added in dry particl, adds recipe quantity tristearin Sour magnesium is uniformly mixed, and is obtained and is always mixed particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, control pressure make tablet hardness within 5~7kg, and tabletting to obtain the final product.
(9) it is coated：Coating powder white stomach dissolution type Opadry 81W68907 is added in purified water, is configured to solid content For 20% Coating Solution, paddle stirring is stirred 45 minutes with screw type.Label is carried out using common transformation coating pan Coating, get Mei Suoshuli Film coated tablets.Wherein, the major parameter of coating process is as follows：Average inlet air temperature is 85 DEG C, average piece Bed tempertaure is 41 DEG C, atomizing pressure 2.5bar, and average coating pan rotating speed is 15~23rpm, 3~4g/ of average material flow Min, weightening 3%~3.5%, obtains the Mei Suoshuli tablets.
(10) it packs：The Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag
Embodiment 7：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 50g, lactose 135g, microcrystalline cellulose 45g, PVP K30 8g, crospovidone (interior to add) 8g are handed over Connection povidone (additional) 8g, magnesium stearate 2g is made 1000 altogether.
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and auxiliary material filler lactose, microcrystalline cellulose mixing are carried out micro- Dusting (grain size is at 5 microns to 100 microns), remaining each auxiliary material smash it through 80 mesh sieve respectively, spare；
(2) with adhesive：8 grams of adhesive PVP K30s are weighed in beaker, adds 92 grams of purified water, stirs to clarify, obtain The binder aqueous solution I of 8% PVP K30, it is spare；
(3) it mixes：By Mei Suoshuli and filler after mixing, the disintegrant crospovidone mixing that Inner is needed to add is added in Uniformly, mixture II is obtained；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into 1h at 65 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：The additional disintegrant crospovidone of the need of recipe quantity is added in dry particl, adds recipe quantity tristearin Sour magnesium is uniformly mixed, and is obtained and is always mixed particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, control pressure make tablet hardness within 5~7kg, and tabletting to obtain the final product.
(9) it is coated：Coating powder white stomach dissolution type Opadry 81W68907 is added in purified water, is configured to solid content For 20% Coating Solution, paddle stirring is stirred 45 minutes with screw type.Label is carried out using common transformation coating pan Coating, get Mei Suoshuli Film coated tablets.Wherein, the major parameter of coating process is as follows：Average inlet air temperature is 85 DEG C, average piece Bed tempertaure is 41 DEG C, atomizing pressure 2.5bar, and average coating pan rotating speed is 15~23rpm, 3~4g/ of average material flow Min, weightening 3%~3.5%, obtains the Mei Suoshuli tablets.
(10) it packs：The Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.
Embodiment 8：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 25g, lactose 30g, microcrystalline cellulose 120g, PVP K30 6g, crospovidone (interior to add) 3g are handed over Connection povidone (additional) 3g, magnesium stearate 2g is made 1000 altogether.
Preparation method：
With adhesive：6 grams of adhesive PVP K30s are weighed in beaker, adds 94 grams of purified water, stirs to clarify, obtain 6% The binder aqueous solution I of PVP K30；Remaining preparation method is the same as embodiment 5.
Embodiment 9：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 25g, cornstarch 200g, hydroxypropyl methylcellulose 6g, croscarmellose sodium (interior to add) 2.5g, Croscarmellose sodium (additional) 2.5g, magnesium stearate 0.8g is made 1000 altogether.
Preparation method：
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and auxiliary material filler cornstarch are mixed and are micronized (grain Diameter is at 5 microns to 100 microns), remaining each auxiliary material smash it through respectively 80 mesh sieve, it is spare；
(2) with adhesive：6 grams of adhesive hydroxypropyl methylcelluloses are weighed in beaker, adds 94 grams of purified water, stirs to clear Clearly, the binder aqueous solution I of 6% hydroxypropyl methylcellulose is obtained, it is spare；
(3) it mixes：By Mei Suoshuli and filler after mixing, the disintegrant crospovidone mixing that Inner is needed to add is added in Uniformly, mixture II is obtained；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into 2h at 60 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：The additional disintegrant crospovidone of the need of recipe quantity is added in dry particl, adds recipe quantity tristearin Sour magnesium is uniformly mixed, and is obtained and is always mixed particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, control pressure make tablet hardness within 5~7kg, and tabletting to obtain the final product.
(9) it is coated：Coating powder white stomach dissolution type Opadry 81W68907 is added in purified water, is configured to solid content For 20% Coating Solution, paddle stirring is stirred 45 minutes with screw type.Label is carried out using common transformation coating pan Coating, get Mei Suoshuli Film coated tablets.Wherein, the major parameter of coating process is as follows：Average inlet air temperature is 85 DEG C, average piece Bed tempertaure is 41 DEG C, atomizing pressure 2.5bar, and average coating pan rotating speed is 15~23rpm, 3~4g/ of average material flow Min, weightening 3%~3.5%, obtains the Mei Suoshuli tablets.
(10) it packs：The Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.
Embodiment 10：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 100g, lactose 40g, microcrystalline cellulose 80g, PVP K30 12g, crospovidone (interior to add) 7g, Crospovidone (additional) 7g, magnesium stearate 3g is made 1000 altogether.
Preparation method：With adhesive：12 grams of adhesive PVP K30s are weighed in beaker, add 88 grams of purified water, stirring is extremely Clarification obtains the binder aqueous solution I of 12% PVP K30；Remaining preparation method is the same as embodiment 5.
Embodiment 11：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 100g, lactose 80g, microcrystalline cellulose 40g, PVP K30 7g, crospovidone (interior to add) 6g are handed over Connection povidone (additional) 6g, magnesium stearate 2.5g is made 1000 altogether.
Preparation method：With adhesive：7 grams of adhesive PVP K30s are weighed in beaker, add 93 grams of purified water, stirring is extremely Clarification obtains the binder aqueous solution I of 7% PVP K30；Remaining preparation method is the same as embodiment 5.
Embodiment 12：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 125g, mannitol 50g, methylcellulose 10g, crospovidone (interior to add) 7g, crospovidone are (outer Adding) 7g, magnesium stearate 4g be made 1000 altogether.
Preparation method：
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and auxiliary material filler mannitol are mixed and are micronized (grain size At 5 microns to 100 microns), remaining each auxiliary material smash it through respectively 80 mesh sieve, it is spare；
(2) with adhesive：10 grams of adhesive methylcellulose are weighed in beaker, adds 90 grams of purified water, stirs to clarify, The binder aqueous solution I of 10% hydroxypropyl methylcellulose is obtained, it is spare；
(3) it mixes：By Mei Suoshuli and filler after mixing, the disintegrant crospovidone mixing that Inner is needed to add is added in Uniformly, mixture II is obtained；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into 2h at 60 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：The additional disintegrant crospovidone of the need of recipe quantity is added in dry particl, adds recipe quantity tristearin Sour magnesium is uniformly mixed, and is obtained and is always mixed particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, control pressure make tablet hardness within 5~7kg, and tabletting to obtain the final product.
(9) it is coated：Coating powder white stomach dissolution type Opadry 81W68907 is added in purified water, is configured to solid content For 20% Coating Solution, paddle stirring is stirred 45 minutes with screw type.Label is carried out using common transformation coating pan Coating, get Mei Suoshuli Film coated tablets.Wherein, the major parameter of coating process is as follows：Average inlet air temperature is 85 DEG C, average piece Bed tempertaure is 41 DEG C, atomizing pressure 2.5bar, and average coating pan rotating speed is 15~23rpm, 3~4g/ of average material flow Min, weightening 3%~3.5%, obtains the Mei Suoshuli tablets.
(10) it packs：The Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.
Embodiment 13：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 125g, lactose 60g, microcrystalline cellulose 60g, PVP K30 10g, sodium carboxymethyl starch (interior to add) 10g, sodium carboxymethyl starch (additional) 10g, magnesium stearate 3g are made 1000 altogether.
Preparation method：.
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and auxiliary material filler mannitol are mixed and are micronized (grain size At 5 microns to 100 microns), remaining each auxiliary material smash it through respectively 80 mesh sieve, it is spare；
(2) with adhesive：10 grams of adhesive methylcellulose are weighed in beaker, adds 90 grams of purified water, stirs to clarify, The binder aqueous solution I of 10% hydroxypropyl methylcellulose is obtained, it is spare；
(3) it mixes：By Mei Suoshuli and filler after mixing, the disintegrating agent carboxymethyl base sodium starch that adding in needs Inner to add is mixed It closes uniformly, obtains mixture II；
(4) softwood processed and granulation：The binder aqueous solution I of recipe quantity is added in mixture II, softwood is made, by gained Softwood crosses 18 mesh stainless steel sieve series grains, obtains wet granular；
(5) it is dry：Drug wet granular obtained in step (4) is dried into 2h at 60 DEG C；
(6) whole grain：18 mesh stainless steels sieve whole grain will be crossed by dry drug granule, obtain dry particl；
(7) it is total mixed：The additional disintegrating agent carboxymethyl base sodium starch of the need of recipe quantity is added in dry particl, it is hard to add recipe quantity Fatty acid magnesium is uniformly mixed, and is obtained and is always mixed particle；
(8) tabletting：According to content of dispersion measured by total mixed particle, calculate the theoretical tablet weight, tablet press machine is adjusted to suitable fills out Charge, control pressure make tablet hardness within 5~7kg, and tabletting to obtain the final product.
(9) it is coated：Coating powder white stomach dissolution type Opadry 81W68907 is added in purified water, is configured to solid content For 20% Coating Solution, paddle stirring is stirred 45 minutes with screw type.Label is carried out using common transformation coating pan Coating, get Mei Suoshuli Film coated tablets.Wherein, the major parameter of coating process is as follows：Average inlet air temperature is 85 DEG C, average piece Bed tempertaure is 41 DEG C, atomizing pressure 2.5bar, and average coating pan rotating speed is 15~23rpm, 3~4g/ of average material flow Min, weightening 3%~3.5%, obtains the Mei Suoshuli tablets.
(10) it packs：The Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.
Embodiment 14：Quality evaluation
1st, performance evaluation
To totally 9 samples described in 5- of embodiment of the present invention embodiments 13, character, hardness, friability, the piece method of double differences are carried out Different, dissolution rate inspection in order to carry out performance evaluation to the preparation-obtained Mei Suoshuli of the present invention, the results are shown in Table 11
11 Mei Suoshuli piece performances of table are evaluated
Table 11 the results show that the characters of 9 batches of samples, hardness, friability, tablet weight variation meet the requirements, and dissolution rate compared with Height, and can reach 90%, it meets the requirements.
2nd, influence factor experiment in 10 days：
Next, Mei Suoshuli pieces (Film coated tablets) are prepared to above-described embodiment 11 carries out influence factor experiment, tool Body is as follows：
The Mei Suoshuli Film coated tablets (lot number 131101) of 100mg specifications is uncovered in culture dish, high temperature (60 DEG C), It places 10 days under the conditions of high humidity (RH92.5%, 25 DEG C), strong light (4500lx ± 500lx), was sampled in the 5th, 10 day, observe preparation The projects such as appearance, content, dissolution rate, related substance, weight-loss ratio, and be compared with the inspection data of sample before investigation, it detects It the results are shown in Table 12.
12 Mei Suoshuli Film coated tablets of table (100mg/ pieces) (lot number 131101) influence factor result of the test
Influence factor result of the test shows：Film coated tablets is placed 10 days under high temperature, high humidity, illumination, content, related substance No conspicuousness variation, quality is basicly stable, shows that prescription science is feasible, rational technology, favorable reproducibility.But 10 days films of high humidity There is the slight moisture absorption on garment piece surface, and dissolution rate is declined, it is noted that moisture-proof when prompting to select to pack.Therefore, product needs to seal It is stored at dry.
3rd, the selection of interior packaging material：
Next, to the Mei Suoshuli Film coated tablets of above-mentioned 100mg specifications, 3 batches are produced, lot number is respectively 131201, 131202nd, 131203 the comparative studies of four kinds of packagings, have been carried out respectively, are intended choosing packaging for four kinds and are followed successively by：Polyvinyl chloride (PVC) steeps Cover, PVC bubble-caps+two-sided composite aluminium film bag, two-sided composite aluminium film bag and plastic bottle.Then, will be respectively adopted four kinds packaging it is thin Film garment piece is placed 6 months under the conditions of temperature is 40 DEG C ± 2 DEG C, relative humidity is 75% ± 5%, accelerate 6 months Comparison is investigated, and is sampled respectively at the 1st, 2,3, June, has been carried out the detection of each inspection target of stability test, accelerates the reality of 6 months It tests data and is shown in Table 13.
13 Mei Suoshuli Film coated tablets of table (100mg/ pieces, PVC bubble-caps+two-sided composite aluminium film bag) accelerates the experiment of 6 months As a result
After accelerating 6 months, the content of four kinds of packagings, related substance dissolution rate are all without significant changes.PVC blister packages and modeling The piece sub-pieces of material bottle packaging is significantly increased again, both slice, thin pieces packed is prompted to have the different degrees of moisture absorption, it may be possible to because For plastic bottle and the poor air-tightness of PVC blister packages, it is affected by humidity.Although each finger of two-sided composite aluminium film bag packaging Mark variation is little, but due to not easy to maintain behind Kaifeng, so not using.The slice, thin piece of PVC bubble-caps+two-sided composite membrane aluminium bag packaging, Appearance character, content, related substance and dissolution rate are all more stable.It can be seen that PVC bubble-caps+two-sided composite aluminium film bag packs water-fast steaming The long-time stability of this product can be effectively ensured in permeability to gas, favorable sealing property.Therefore, selection PVC bubble-caps+two-sided clad aluminum Film bag is packaged as the optimal interior packaging material of Mei Suoshuli Film coated tablets.
In the description of the present invention, it is to be understood that term " first ", " second " are only used for description purpose, and cannot It is interpreted as indicating or implies relative importance or imply the quantity of the technical characteristic indicated by indicating.Define as a result, " the One ", one or more this feature can be expressed or be implicitly included to the feature of " second ".In the description of the present invention, " multiple " are meant that two or more, unless otherwise specifically defined.
In the description of this specification, reference term " one embodiment ", " example ", " is specifically shown " some embodiments " The description of example " or " some examples " etc. means specific features, structure, material or the spy for combining the embodiment or example description Point is contained at least one embodiment of the present invention or example.In the present specification, schematic expression of the above terms are not It must be directed to identical embodiment or example.Moreover, particular features, structures, materials, or characteristics described can be in office It is combined in an appropriate manner in one or more embodiments or example.In addition, without conflicting with each other, the skill of this field Art personnel can tie the different embodiments or examples described in this specification and the feature of different embodiments or examples It closes and combines.
Although the embodiments of the present invention has been shown and described above, it is to be understood that above-described embodiment is example Property, it is impossible to limitation of the present invention is interpreted as, those of ordinary skill in the art within the scope of the invention can be to above-mentioned Embodiment is changed, changes, replacing and modification.

Claims (7)

1. a kind of Mei Suoshuli tablets, which is characterized in that including：
Mei Suoshuli 25-125 parts by weight by micronization processes；
Microcrystalline cellulose by micronization processes and the common 50-200 parts by weight of the lactose Jing Guo micronization processes；
PVP K30 6-12 parts by weight；
The common 5-20 parts by weight of crospovidone that the crospovidone and outer addition that interior addition adds in add in；And
Magnesium stearate 0.8-4 parts by weight.
2. Mei Suoshuli tablets according to claim 1, which is characterized in that according to parts by weight, the Mei Suoshuli pieces Agent is selected from one of following：
50 parts by weight of Mei Suoshuli by micronization processes, 50 parts by weight of lactose by micronization processes, by micronizing 100 parts by weight of microcrystalline cellulose of processing, 8 parts by weight of PVP K30, the crospovidone and outer addition that interior addition adds in add The crospovidone entered totally 12 parts by weight, 2.5 parts by weight of magnesium stearate；
50 parts by weight of Mei Suoshuli by micronization processes, 113 parts by weight of lactose by micronization processes, by micronizing 57 parts by weight of microcrystalline cellulose of processing, 8 parts by weight of PVP K30, the crospovidone and outer addition that interior addition adds in add in Crospovidone totally 12 parts by weight, 2.4 parts by weight of magnesium stearate；
50 parts by weight of Mei Suoshuli by micronization processes, 135 parts by weight of lactose by micronization processes, by micronizing 45 parts by weight of microcrystalline cellulose of processing, 8 parts by weight of PVP K30, the crospovidone and outer addition that interior addition adds in add in Crospovidone totally 16 parts by weight, 2 parts by weight of magnesium stearate；
25 parts by weight of Mei Suoshuli by micronization processes, 30 parts by weight of lactose by micronization processes, by micronizing 120 parts by weight of microcrystalline cellulose of processing, 6 parts by weight of PVP K30, the crospovidone and outer addition that interior addition adds in add The crospovidone entered totally 6 parts by weight, 2 parts by weight of magnesium stearate；
100 parts by weight of Mei Suoshuli by micronization processes, 40 parts by weight of lactose by micronization processes, by micronizing 80 parts by weight of microcrystalline cellulose of processing, 12 parts by weight of PVP K30, the crospovidone and outer addition that interior addition adds in add The crospovidone entered totally 14 parts by weight, 3 parts by weight of magnesium stearate；
100 parts by weight of Mei Suoshuli by micronization processes, 80 parts by weight of lactose by micronization processes, by micronizing 40 parts by weight of microcrystalline cellulose of processing, 7 parts by weight of PVP K30, the crospovidone and outer addition that interior addition adds in add in Crospovidone totally 12 parts by weight, 2.5 parts by weight of magnesium stearate.
A kind of 3. method of Mei Suoshuli tablets prepared described in claims 1 or 2, which is characterized in that including：
(1) Mei Suoshuli, microcrystalline cellulose, lactose are mixed, and obtained mixture is subjected to micronization processes, to obtain The mixture micro powder granule that grain size is 5 microns to 100 microns is obtained, crospovidone, PVP K30 and magnesium stearate are distinguished into powder 80 mesh sieve is crossed after broken, it is spare；
(2) PVP K30 is mixed with purified water, with the PVP K30 aqueous solution that obtained mass fraction is 6%~12% I, it is spare；
(3) the mixture micro powder granule with the interior crospovidone added is mixed, obtains mixture II；
(4) the PVP K30 aqueous solution I is added in the mixture II, and softwood is made in obtained mixture, it will Gained softwood crosses 18 mesh stainless steel sieve series grains, to obtain wet granular；
(5) at 55 DEG C~65 DEG C, the wet granular is dried into 1~4h, then crosses 18 mesh stainless steels sieve whole grain, it is dry to obtain Particle；
(6) dry particl with additional crospovidone is mixed, then obtained mixture is mixed with magnesium stearate, with Just the medicinal mixture is obtained；
(7) content of dispersion of the medicinal mixture is measured, and is calculated the theoretical tablet weight, then presses the medicinal mixture Piece, to obtain the Mei Suoshuli labels；
(8) coating powder is added in purified water, is configured to the Coating Solution that solid content is 20%, it is then molten using the coating Liquid is coated processing to the Mei Suoshuli labels, to obtain the Mei Suoshuli tablets.
4. according to the method described in claim 3, it is characterized in that, further comprise：
The Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap and two-sided composite aluminium film bag.
5. according to the method described in claim 3, it is characterized in that, when tabletting piece is controlled again in theoretical piece ± 5% range of weight Interior, hardness is controlled in 5~7kg.
6. according to the method described in claim 3, it is characterized in that, using common transformation coating pan to the Mei Suoshuli labels The Cotton seeds are carried out, wherein, the parameter of the Cotton seeds is as follows：Average inlet air temperature is 85 DEG C, average piece bed tempertaure It is 41 DEG C, atomizing pressure 2.5bar, average coating pan rotating speed is 15~23rpm, averagely 3~4g/min of material flow,
Based on the gross mass of the Mei Suoshuli labels, according to mass percent meter, coating weight gain is 3.0~3.5%.
7. according to the method described in claim 3, it is characterised in that it includes：
(1) Mei Suoshuli with lactose and microcrystalline cellulose is mixed, and obtained mixture is subjected to micronization processes, so as to The mixture micro powder granule that grain size is 5 microns to 100 microns is obtained, by crospovidone, PVP K30 and magnesium stearate 80 mesh sieve is smashed it through respectively, it is spare；
(2) PVP K30 is mixed with purified water, it is standby with the PVP K30 aqueous solution I that obtained mass fraction is 6%~12% With；
(3) the mixture micro powder granule with the interior crospovidone added is mixed, obtains the mixture II；
(4) the PVP K30 aqueous solution I is added in the mixture II, and softwood is made in obtained mixture, it will Gained softwood crosses 18 mesh stainless steel sieve series grains, obtains the wet granular；
(5) at 55 DEG C~65 DEG C, the wet granular is dried into 1~4h, 18 mesh stainless steels sieve whole grain is then crossed, to obtain State dry particl；
(6) dry particl with additional crospovidone is mixed, and obtained mixture is mixed with magnesium stearate, with Just the medicinal mixture is obtained；
(7) content of dispersion of the medicinal mixture is measured, and is calculated the theoretical tablet weight, based on the theoretical piece weight, by the drug Mixture carries out tabletting, to obtain the Mei Suoshuli labels；
(8) coating powder white stomach dissolution type Opadry 81W68907 is added in purified water, it is 20% to be configured to solid content Coating Solution stirs paddle stirring 45 minutes, then using common transformation coating pan to described in label progress with screw type Cotton seeds, to obtain the Mei Suoshuli tablets,
Wherein, the parameter of the Cotton seeds is as follows：Average inlet air temperature is 85 DEG C, and average piece bed tempertaure is 41 DEG C, atomization pressure Power is 2.5bar, and average coating pan rotating speed is 15~23rpm, averagely 3~4g/min of material flow,
Coating weight gain 3%~3.5%；
(9) the Mei Suoshuli tablets are packed using polyvinyl chloride bubble-cap and two-sided composite aluminium film bag.
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