CN105434388B - Mei Suoshuli Film coated tablets - Google Patents
Mei Suoshuli Film coated tablets Download PDFInfo
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- CN105434388B CN105434388B CN201410438406.8A CN201410438406A CN105434388B CN 105434388 B CN105434388 B CN 105434388B CN 201410438406 A CN201410438406 A CN 201410438406A CN 105434388 B CN105434388 B CN 105434388B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
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- 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
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- 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
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Abstract
The invention discloses Mei Suoshuli Film coated tablets, the Mei Suoshuli Film coated tablets includes：Mei Suoshuli and pharmaceutically acceptable auxiliary material.The Mei Suoshuli Film coated tablets dissolution rate of the present invention 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.In addition, the preparation method the present invention also provides Mei Suoshuli Film coated tablets.
Description
Technical field
The present invention relates to pharmaceutical fields, are related to Mei Suoshuli Film coated tablets, and in particular, to Mei Suoshuli Film coated tablets,
And the preparation method of Mei Suoshuli Film coated tablets.
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 the Mei Suoshuli of a kind of good effect, dissolution rate height, bioavilability height, stable quality, Small side effects
Preparation.
In one aspect of the invention, the present invention provides a kind of Mei Suoshuli Film coated tablets.Implementation according to the present invention
Example, the Mei Suoshuli Film coated tablets include：Mei Suoshuli；And pharmaceutically acceptable auxiliary material.Inventor has found, of the invention
Mei Suoshuli Film coated tablets dissolution rate is high, disintegration time is short, Small side effects, stable quality, can effectively play anti-inflammatory, analgesia,
The effect of antipyretic, 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 be selected from cornstarch, microcrystalline cellulose, mannitol at least one
Kind.Thereby, it is possible to improve the compressibility of drug, the dose deviations of main component are reduced, promote disintegration and dissolution.Particularly, it sends out
A person of good sense has found that, when selecting microcrystalline cellulose for filler, only drugs compressibility is not good, and disintegration rate is fast, and dissolution rate is high, and can
Improve the hardness of Film coated tablets and unilateral finish.
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 film-coatings can be promoted
The disintegration and dissolution of piece.Particularly, inventor has found, when using PVP K30 as adhesive, Mei Suoshuli Film coated tablets
Disintegration rate it is very fast, dissolution rate is higher.
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 Film coated tablets can fater disintegration, be conducive to U.S.
The dissolution of Suo Shuli.Particularly, inventor has found, when using crospovidone for disintegrant, Mei Suoshuli Film coated tablets
Disintegration rate is very fast, and dissolution rate is higher.
According to an embodiment of the invention, the lubricant is magnesium stearate.The unilateral light of Mei Suoshuli Film coated 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 Core formulation composition of the Mei Suoshuli Film coated tablets can
To 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 parts by weight, the lubricant 0.8-4 parts by weight.The disintegration rate of Mei Suoshuli is fast as a result, dissolution rate
Height, bioavilability is high, and stable quality, toxic side effect are small.
According to a particular embodiment of the invention, according to parts by weight, the Core formulation group of the Mei Suoshuli Film coated tablets
Into can include：Mei Suoshuli 25-150 parts by weight, microcrystalline cellulose 50-200 parts by weight, PVP K30 6-12 parts by weight are handed over
Join povidone 5-20 parts by weight, magnesium stearate 0.8-4 parts by weight.The disintegration rate of Mei Suoshuli is fast as a result, dissolution rate is high, raw
Object availability is high, and stable quality, toxic side effect are small.
A specific example according to the present invention, according to parts by weight, the Core formulation of the Mei Suoshuli Film coated tablets
Composition includes：50 parts by weight of Mei Suoshuli, 170 parts by weight of microcrystalline cellulose, 8 parts by weight of PVP K30,12 weight of crospovidone
Measure part, 2.5 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Core formulation of the Mei Suoshuli Film coated tablets
Composition includes：50 parts by weight of Mei Suoshuli, 150 parts by weight of microcrystalline cellulose, 8 parts by weight of PVP K30,12 weight of crospovidone
Measure part, 2.4 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Core formulation of the Mei Suoshuli Film coated tablets
Composition includes：50 parts by weight of Mei Suoshuli, 120 parts by weight of microcrystalline cellulose, 10 parts by weight of PVP K30,5 weight of crospovidone
Measure part, 1 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Core formulation of the Mei Suoshuli Film coated tablets
Composition includes：25 parts by weight of Mei Suoshuli, 200 parts by weight of microcrystalline cellulose, 6 parts by weight of PVP K30,16 weight of crospovidone
Measure part, 0.8 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Core formulation of the Mei Suoshuli Film coated tablets
Composition includes：75 parts by weight of Mei Suoshuli, 150 parts by weight of microcrystalline cellulose, 12 parts by weight of PVP K30, crospovidone 20
Parts by weight, 4 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Core formulation of the Mei Suoshuli Film coated tablets
Composition includes：100 parts by weight of Mei Suoshuli, 120 parts by weight of microcrystalline cellulose, 7 parts by weight of PVP K30, crospovidone 12
Parts by weight, 2.5 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Core formulation of the Mei Suoshuli Film coated tablets
Composition includes：100 parts by weight of Mei Suoshuli, 120 parts by weight of microcrystalline cellulose, 10 parts by weight of PVP K30, crospovidone 14
Parts by weight, 3 parts by weight of magnesium stearate.
A specific example according to the present invention, according to parts by weight, the Core formulation of the Mei Suoshuli Film coated tablets
Composition includes：125 parts by weight of Mei Suoshuli, 90 parts by weight of microcrystalline cellulose, 7 parts by weight of PVP K30,10 weight of crospovidone
Measure part, 2 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.And microcrystalline cellulose not only serves as filler,
And have the performance of disintegrant, it chooses microcrystalline cellulose and can reach good result of extraction.And inventor has found, works as selection
When microcrystalline cellulose is filler, only drugs compressibility is not good, and disintegration rate is fast, and dissolution rate is high, and can improve Film coated tablets
Hardness and unilateral finish.In addition, it according to an embodiment of the invention, as adhesive and is used when using PVP K30
When crospovidone is disintegrant, the disintegration rate of Mei Suoshuli Film coated tablets is very fast, and dissolution rate is higher.
In another aspect of this invention, the present invention provides the methods for preparing foregoing Mei Suoshuli Film coated tablets.
According to an embodiment of the invention, this method includes the following steps：Mei Suoshuli is subjected to micronization processes, and the U.S. that will be obtained
Suo Shuli micro powder granules and the mixing of pharmaceutically acceptable auxiliary material, to obtain medicinal mixture；By the medicinal mixture into
Row tabletting, to obtain Mei Suoshuli labels；Processing is coated to the Mei Suoshuli plain pieces, it is thin to obtain Mei Suoshuli
Film garment piece.Inventor has found, using this method of the present invention, can fast and effeciently prepare foregoing Mei Suoshuli
Film coated tablets, preparation process is simple, easy to operate, easily controllable, is suitble to industrialized production, while the Mei Suoshu prepared
Sharp Film coated tablets disintegration rate is fast, and dissolution rate is high, and stable quality, Small side effects, can effective for treatment inflammation, analgesia or
Analgesic.In the preceding processing of supplementary material, first Mei Suoshuli and filler are mixed after being micronized, then Mei Suoshuli obtained
Film coated tablets, relative to Mei Suoshuli Film coated tablets made from the Mei Suoshuli without micronizing, dissolution rate notable can obtain
To improvement.
According to an embodiment of the invention, the method for preparing Mei Suoshuli Film coated tablets may further include：Using polychlorostyrene
Ethylene bubble-cap+two-sided composite aluminium film bag packs the Mei Suoshuli Film coated tablets.Leakproofness is preferable as a result, Neng Gouyou
Effect prevents the Mei Suoshuli Film coated tablets moisture absorptions, is conducive to the long-term storage of Mei Suoshuli Film coated tablets.
According to an embodiment of the invention, the method for preparing Mei Suoshuli Film coated 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 Film coated tablets,
According to an embodiment of the invention, it may further include：
(9) the Mei Suoshuli Film coated tablets is packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.
Thereby, it is possible to quickly and effectively prepare foregoing Mei Suoshuli Film coated tablets.Wherein, by by U.S. rope
Shu Li carries out micronization processes, and Mei Suoshuli is enabled to uniformly disperse the dissolution rate in auxiliary material, effectively improving Mei Suoshuli,
Disintegrant is added in two times, the dissolution rate of Mei Suoshuli Film coated tablets can also be greatly improved.
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 Film coated tablets.Result described in the embodiment of the present invention can be seen that the work using addition inside and outside disintegrant
Skill, relative to disintegrant only with the technique of interior addition, dissolution rate significantly improves.Therefore determine dosage and the addition side of disintegrant
Formula is：The interior dosage of disintegrant is the 1/2 of disintegrant recipe quantity, and outer dosage is another the 1/2 of disintegrant recipe quantity.According to the present invention
Embodiment, when tabletting controls piece again in the range of theoretical piece weight ± 5%, and hardness is controlled in 5~7kg.The U.S. obtained as a result,
Suo Shuli Film coated tablets appearance, piece meet the requirements, and disintegration rate is fast again etc., and dissolution rate is high.
According to an embodiment of the invention, piece is controlled again during tabletting in the range of theoretical piece weight ± 5%, hardness is controlled 5
~7kg.The Mei Suoshuli Film coated tablets appearance that obtains 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 Film coated tablets it is unilateral bright and clean, appearance meets the requirements.
By the preparation-obtained Mei Suoshuli Film coated tablets of the present invention, character, hardness, friability, tablet weight variation accord with
Requirement is closed, and dissolution rate is higher, and can reach 90%, meets the requirements.
10 days influence factor result of the tests of Mei Suoshuli Film coated tablets show：Film coated tablets is under high temperature, high humidity, illumination
It places 10 days, content, related substance change without conspicuousness, and quality is basicly stable, shows that prescription science is feasible, rational technology, again
Existing property is good.But there is the slight moisture absorption on 10 days Film coated tablets surfaces of high humidity, and dissolution rate is declined, and prompt during selection packaging it is noted that preventing
Tide.Therefore, product needs to store at hermetically drying.
Further, according to an embodiment of the invention, the interior packaging material of Mei Suoshuli Film coated tablets of the present invention is carried out
Selection, packs the Mei Suoshuli Film coated tablets using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.It seals as a result,
Property is preferable, can effectively prevent the Mei Suoshuli Film coated tablets moisture absorptions, the long-time stability of this product can be effectively ensured, be conducive to Mei Suo
The long-term storage of Shu Li Film coated tablets.
A specific example according to the present invention, the method for preparing Mei Suoshuli Film coated tablets include the following steps：
(1) Mei Suoshuli with 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 is obtained, by crospovidone, PVP K30 and magnesium stearate point
80 mesh sieve is not smashed it through, 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 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 stirs paddle stirring 45 minutes with screw type, then using common transformation coating pan to Mei Suoshu
Sharp label carries out the Cotton seeds, to obtain the Mei Suoshuli Film coated 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 Film coated tablets is packed using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag.
According to an embodiment of the invention, the invention has the advantages that：
1st, according to an embodiment of the invention, by using microcrystalline cellulose as filler, only drugs compressibility is not good, collapses
It is fast to solve speed, dissolution rate is high, and can improve the hardness of Film coated tablets and unilateral finish, accelerates Mei Suoshuli Film coated tablets
Disintegration, so as to improve the dissolution rate of Mei Suoshuli.When use PVP K30 as adhesive and use crospovidone for
During disintegrant, the disintegration rate of Mei Suoshuli Film coated tablets is very fast, and dissolution rate is higher.
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 filler, then mix, adopt with other auxiliary materials again
Manufactured Mei Suoshuli Film coated tablets, dissolution rate can significantly be improved in this way.
3rd, according to an embodiment of the invention, the present invention by crospovidone by adding (i.e. interior addition and outer addition) twice
Into medicinal mixture, additional disintegrant can promote the disintegration of particle, and interior plus disintegrant can then accelerate the dispersion of particle, this side
Method 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 particle are conducive to improve dissolution rate.
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 Film coated tablets appearance that obtains 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 Film coated tablets, and do not influence the disintegration time and dissolution rate of Mei Suoshuli Film coated tablets, also
Preferable shaded effect can be played.
6th, using this method of the present invention, foregoing Mei Suoshuli film-coatings can fast and effeciently be prepared
Piece, preparation process is simple, easy to operate, easily controllable, is suitble to industrialized production, while the Mei Suoshuli films prepared
Garment piece disintegration rate 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：Formulation study
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 Film coated tablets of 100mg/ pieces is ground
Study carefully, specifically, due to Mei Suoshuli raw materials aqueous solubility and mobility inequality, consider that adding in water soluble adjuvant and disintegrant promotees
Into dissolution, 9 prescriptions are devised, are shown in Table 1.
The different Formulation of table 1
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 to be configured to 8% PVP K30 aqueous solution (g/g), and "-" expression is without respective sets
Point.
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 makes the tablet hardness of Film coated tablets, and tabletting within 5~7kg 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 2.
The dissolution rate comparison of 2 each Film coated tablets Core formulation of table
| Prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
| Dissolution rate (%) | 80.6 | 78.8 | 74.9 | 82.3 | 80.5 | 72.0 | 82.5 | 78.6 | 77.9 |
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 5, prescription 7, dissolution rate has reached more than 80%.Due to Mei Suoshuli poorly water-solubles, and hydroxyl
Third methylcellulose has the molten effect of resistance, and dissolution rate may be influenced during sample keeps sample, it is in water needed for complete swelling in addition
Time is longer, is unfavorable for industrialized production, thus preferably its as adhesive.But due to previous experiments research shows that：Individually
During using lactose as filler, the big production of industry will appear sliver phenomenon, so the present invention does not select in the auxiliary material selection of diluent
Use lactose.And microcrystalline cellulose not only serves as filler, and has the performance of disintegrant, chooses microcrystalline cellulose and can reach
Good result of extraction.
Therefore originally determine based on prescription 4 and prescription 7, further investigate optimum amount, the bonding of screening filler
The concentration of agent and the addition manner for improving disintegrant, advanced optimize prescription and preparation process.
Embodiment 2：The Mei Suoshuli Film coated tablets prescription and process optimization of 100mg specifications
This research is promulgated according to 2010 editions dosage form requirements to Film coated tablets of Chinese Pharmacopoeia with reference to CDE《Chemicals system
Basic fundamental guideline is studied in agent》, the characteristics of combination film garment piece, with character, hardness, friability, disintegration time, dissolution rate
Deng for inspection target, the type and dosage for using this product prescription auxiliary material have carried out further screening.
(1) screening of filler
The ratio and dosage of microcrystalline cellulose are adjusted, investigating diluent, (herein, " filler " and " diluent " can be with
It is used interchangeably) influence of the different amounts to tabletting formability and dissolution rate, specific prescription and result are as follows：
Using microcrystalline cellulose as diluent, the prescription of microcrystalline cellulose different amounts is shown in Table 3, shown in table 3 for this research
To prepare the recipe quantity of 1000 Mei Suoshuli Film coated tablets.According to prescription shown in table 3 and the preparation side described in embodiment 1
Method carries out pelletizing press sheet with the batch of 1000/batches, and theoretical piece weight is 240mg, and it is thin then to measure the Mei Suoshuli prepared
Hardness, friability, disintegration time and the dissolution rate of film garment piece screen filler.It the results are shown in Table 3.
The screening prescription and measurement result of 3 filler of table
For microcrystalline cellulose by the dosage of above-mentioned 4 prescriptions, dissolution rate can reach 80% it can be seen from the result of table 3
More than, wherein best with the disintegration of prescription 12 and dissolution rate.
(2) screening of adhesive
PVP-K30 is chosen as adhesive, and the aqueous solution for preparing various concentration compares its bonding effect and grinds
Study carefully, it is specific as follows：
According to the prescription shown in table 4 and the preparation method in embodiment 1, the piece of Mei Suoshuli Film coated tablets is prepared
Core observes Mei Suoshuli dry particl situations in preparation process, and measures the label of Mei Suoshuli Film coated tablets prepared
Hardness, friability, disintegration time and dissolution rate, prescription and measurement result are shown in Table 4, wherein, prescription shown in table 4 is prepares 1000
The recipe quantity of the label of Mei Suoshuli Film coated tablets.
Wherein, in prescription 14, 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 15, 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 16,
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 17, 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 18, 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 screening of 4 adhesive of table
From the results shown in Table 4, when binder concn is 4%, softwood is done, and loosely, has been not easy to glue, due to
The dry particl arrived is small and loose, and fine powder is more, poor fluidity, be easy to cause that tablet weight variation is unqualified, and poor compressibility causes hardness
Relatively low, friability is high, can not meet coating demand；When binder dosage reaches 15%, obtained softwood is harder, is not easy
Sieve, viscous sieve is more serious, and mostly strip, and extends disintegration time；And when a concentration of the 6%~12% of adhesive,
Obtained softwood dry and wet degree is moderate, the particle rounding for being easily sieved and obtaining, and uniformly, good fluidity is easy to carry out tabletting, obtain
The inspection targets such as tablet hardness, friability, disintegration time to Film coated tablets are qualified, therefore, select adhesive as PVPK30,
Its a concentration of 6%~12%, the dosage of adhesive PVPK30 is in prescription：6g~12g/1000 pieces.
(3) screening of disintegrant
In the present embodiment, the dosage of disintegrant and the addition manner of disintegrant have been investigated to Mei Suoshuli Film coated tablets
The influence of label, it is specific as follows：
According to the formula shown in table 5 and the preparation method in embodiment 1, Mei Suoshuli Film coated tablets pieces are prepared
Core.It should be noted that in the present embodiment, the addition manner of disintegrant is two kinds：Interior addition and outer addition, interior addition be
Disintegrant is added in step (3), outer addition refers to add in disintegrant in step (7).Then the Mei Suoshu prepared is measured
Hardness, friability, disintegration time and the dissolution rate of sharp Film coated tablets label, measurement result are shown in Table 6.Wherein, the formula shown in table 5
To prepare the recipe quantity of 100 Mei Suoshuli Film coated tablets labels.
The prescription screening of 5 disintegrant of table
The prescription screening experimental result of 6 disintegrant of table
| Prescription | 19 | 20 | 21 | 22 | 23 |
| Hardness (kg) | 6.1 | 5.2 | 6.4 | 6.8 | 5.9 |
| Disintegration time (s) | 64 | 45 | 50 | 39 | 27 |
| Friability (%) | 0.13 | 0.18 | 0.20 | 0.17 | 0.12 |
| Dissolution rate (%) | 91.0 | 93.6 | 93.4 | 92.3 | 96.0 |
From the results shown in Table 6, prescription 20 and 21 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.Using inside and outside addition, additional disintegrant can promote
The disintegration of particle, interior plus disintegrant can then accelerate the dispersion of particle, be conducive to improve dissolution rate.It can be seen from the results above that
The disintegration time and dissolution rate of prescription 23 be attained by it is optimal, therefore determine PVPP dosage and addition manner be：Interior plus 0.7g, outside
Add 0.5g.Therefore, it is prescription 23 to fix tentatively best prescription.
In the present embodiment, the dosage of disintegrant and the addition manner of disintegrant have been investigated to Mei Suoshuli Film coated tablets
The influence of label, it is specific as follows：
According to the formula shown in table 7 and the preparation method in embodiment 1, 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 refers to add in disintegrant in mixing step, and outer addition refers to always mix in step, add in lubricant it
Before, first dry particl and disintegrant are uniformly mixed.
Specifically, when addition in disintegrant progress, it is identical with the addition manner in embodiment 1；
Inside and outside disintegrant progress during addition, by the prescription in table 7, using wet granulation technology, sample is prepared respectively, is made
Preparation Method is 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：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：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 makes Film coated tablets tablet hardness, and tabletting within 5~7kg to obtain the final product.
Then hardness, friability, disintegration time and the dissolution rate of Mei Suoshuli Film coated tablets labels prepared is measured,
Measurement result is shown in Table 7.Wherein, recipe quantity of the formula of prescription 24- prescriptions shown in table 7 28 to prepare 1000 Mei Suoshuli pieces.
The prescription screening of 7 disintegrant of table
From the results shown in Table 7, prescription 24, prescription 25 and 26 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 27 and prescription 28
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.Therefore determine that the dosage of disintegrant and addition manner are：It collapses
The interior dosage for solving agent is the 1/2 of disintegrant recipe quantity, and outer dosage is another the 1/2 of disintegrant recipe quantity.Therefore, prescription is fixed tentatively as place
Side 28.
Embodiment 3：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 28 in embodiment 2, the preparation process of the present invention is advanced optimized, to further improve
The dissolution rate of Mei Suoshuli Film coated tablets label of the present invention.
Specifically, according to prescription 28, two groups of (A groups and B groups) Mei Suoshuli Film coated tablets labels are prepared respectively, prepare A groups
The method of Mei Suoshuli Film coated tablets labels is as described below, preparation method and the A group Mei Suoshuli films of B group Mei Suoshuli tablets
Difference lies in the mixture of main ingredient Mei Suoshuli and auxiliary material filler does not carry out micronization processes to the preparation method of tablet core.
It is specific as follows：
The preparation method of A group Mei Suoshuli Film coated tablets labels is as follows：
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and filler microcrystalline cellulose 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：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 makes Film coated tablets tablet hardness, and tabletting within 5~7kg to obtain the final product.
Then the dissolution rate of Mei Suoshuli Film coated tablets labels prepared is measured, measurement result is shown in Table 8.
Table 8
As shown in Table 8, it is first that Mei Suoshuli and filler crystallite is fine relative to the Mei Suoshuli without micronizing
Dimension element mixing is micronized, then the dissolution rate of Mei Suoshuli Film coated tablets label 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 Film coated tablets piece of the hardness level control of Film coated tablets label in section shown in table 9, then measure different hardness
Friability, dissolution rate and the disintegration time of core, measurement result are shown in Table 9.
Table 9 investigates influence of the hardness to experimental result
As can be known from the results of Table 9：When range of the hardness of Film coated tablets label between 4~7kg, disintegration time and molten
Out-degree is affected by it less；And when hardness is in 7~8kg, dissolution rate reduces；And when hardness is in 4~5kg, friability is big；It examines
Consider Film coated tablets label to also need to be coated, to the more demanding of friability, therefore, the hardness control of Film coated tablets label is existed
5~7kg is comparatively ideal range.
Wherein, prescription 30 is the Mei Suoshuli pieces that specification is 50mg, and prescription is：Mei Suoshuli 50g, microcrystalline cellulose
170g, PVP K30 8g, crospovidone (interior to add) 6g, crospovidone (additional) 6g, magnesium stearate 2.5g.
Prescription 29 is the Mei Suoshuli pieces that specification is 100mg, and prescription is：Mei Suoshuli 100g, microcrystalline cellulose 120g,
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 Film coated tablets tablet hardness is made to carry out tabletting within 4~5kg, 5~6kg, 6~7kg, 7~8kg
Up to the Mei Suoshuli pieces of above-mentioned different hardness.
3rd, art for coating is studied
In order to ensure Film coated tablets quality and conveniently take, often Mei Suoshuli labels (heretofore described label, i.e.,
Refer to the Mei Suoshuli pieces not being coated in above-described embodiment) the suitable clothing layer material of surface layer package, make in Film coated tablets
Drug is isolated from the outside, and obtains in Film coated tablets of the Mei Suoshuli medical surfaces covered with film-coating, so as to reach moisture-proof, keep away
The stability that light, isolation air oxidation, enhancing drug preserve covers the bad odor in Film coated tablets and reduces medicine irritation
Purpose.
(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
130804 batches of Mei Suoshuli Film coated tablets label samples of above-mentioned preparation are taken, by the 5% of label weight, weigh coating
Powder adds purified water that the solution that solid content is 20% is made, and investigates the coating effect of different coating weight gains, and investigation the results are shown in Table 10.
The screening of 10 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 | 78 |
| 3.0% | Coating tablet is fully wrapped around, and color is uniform, and edge is complete | 105 |
| 3.5% | Coating tablet is fully wrapped around, and color is uniform, and edge is complete | 113 |
| 4.0% | Coating tablet is fully wrapped around, and color is uniform, and edge is complete | 171 |
Table 10 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 11 below that basic performance evaluation is carried out to the coating tablet that above-mentioned three kinds of appearances are met the requirements：
11 coating tablet basic performance of table is evaluated
Consider with reference to the result of table 10 and table 11, 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 4：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 50g, microcrystalline cellulose 170g, PVP K30 8g, crospovidone (interior to add) 6g, crospovidone
(additional) 6g, magnesium stearate 2.5g are made 1000 altogether.
Preparation method：
(1) supplementary material pre-treatment：Main ingredient (Mei Suoshuli) and filler microcrystalline cellulose 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：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 makes Film coated tablets tablet hardness, and tabletting within 5~7kg 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 Film coated tablets.
(10) it packs：The Mei Suoshuli Film coated tablets is wrapped using polyvinyl chloride bubble-cap+two-sided composite aluminium film bag
Dress.Embodiment 5：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 50g, microcrystalline cellulose 150g, PVP K30 8g, crospovidone (interior to add) 6g, crospovidone
(additional) 6g, magnesium stearate 2.4g are made 1000 altogether.
Preparation method：With embodiment 5.
Embodiment 6：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 50g, microcrystalline cellulose 120g, PVP K30 10g, crospovidone (interior to add) 2.5g are crosslinked poly- dimension
Ketone (additional) 2.5g, magnesium stearate 1g is made 1000 altogether.
Preparation method：With adhesive：10 grams of adhesive PVP K30s are weighed in beaker, add 90 grams of purified water, stirring is extremely
Clarification obtains the binder aqueous solution I of 10% PVP K30；Remaining preparation method is the same as embodiment 4.
Embodiment 7：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 25g, microcrystalline cellulose 200g, PVP K30 6g, crospovidone (interior to add) 8g, crospovidone
(additional) 8g, magnesium stearate 0.8g are made 1000 altogether.
Preparation method：With adhesive：6 grams of adhesive PVP K30s are weighed in beaker, add 94 grams of purified water, stirring is extremely
Clarification obtains the binder aqueous solution I of 6% PVP K30；Remaining preparation method is the same as embodiment 4.
Embodiment 8：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 75g, microcrystalline cellulose 150g, PVP K30 12g, crospovidone (interior to add) 10g are crosslinked poly- dimension
Ketone (additional) 10g, magnesium stearate 4g 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 4.
Embodiment 9：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 100g, microcrystalline cellulose 120g, PVP K30 7g, crospovidone (interior to add) 6g, crospovidone
(additional) 6g, magnesium stearate 2.5g are 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 4.
Embodiment 10：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 100g, microcrystalline cellulose 120g, PVP K30 10g, crospovidone (interior to add) 7g are crosslinked poly- dimension
Ketone (additional) 7g, magnesium stearate 3g is made 1000 altogether.
Preparation method：With adhesive：10 grams of adhesive PVP K30s are weighed in beaker, add 90 grams of purified water, stirring is extremely
Clarification obtains the binder aqueous solution I of 10% PVP K30；Remaining preparation method is the same as embodiment 4.
Embodiment 11：The preparation of Mei Suoshuli pieces
Prescription：
Mei Suoshuli 125g, microcrystalline cellulose 90g, PVP K30 7g, crospovidone (interior to add) 5g, crospovidone
(additional) 5g, magnesium stearate 2g are 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 4.
Embodiment 12：Quality evaluation
1st, performance evaluation
To totally 8 samples described in 4- of embodiment of the present invention embodiments 11, 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 12.
12 Mei Suoshuli piece performances of table are evaluated
Table 12 the results show that the characters of 8 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 Film coated tablets is prepared to above-described embodiment 4 carries out influence factor experiment, specifically such as
Under：
The Mei Suoshuli Film coated tablets (lot number 131205) of 50mg specifications is uncovered in culture dish, high temperature (60oC),
It places 10 days under the conditions of high humidity (RH 92.5%, 25 DEG C), strong light (4500lx ± 500lx), was sampled in the 5th, 10 day, observation system
The projects such as agent appearance, content, dissolution rate, related substance, weight-loss ratio, and be compared with the inspection data of sample before investigation, it examines
Survey the results are shown in Table 13.
Wherein, impurity 1 is compound, structure shown in the formula I disclosed in Chinese invention patent application CN103553984A
Formula is as follows：
13 Mei Suoshuli Film coated tablets of table (50mg/ pieces) (lot number 131205) influence factor experiment investigation result
3rd, the selection of interior packaging material：
Next, to the Mei Suoshuli Film coated tablets of above-mentioned 50mg specifications, 3 batches are produced, lot number is respectively 131206,
131207th, 131208 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 0th, 1,2,3, June, has been carried out the detection of each inspection target of stability test, is accelerated 6 months
Experimental data is shown in Table 14.
14 Mei Suoshuli Film coated tablets of table (50mg/ pieces, PVC bubble-caps+two-sided composite aluminium film bag) accelerates the experiment knot of 6 months
Fruit
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 Film coated tablets, including label and coating, which is characterized in that the label includes：
Mei Suoshuli 25-125 parts by weight by micronization processes；
Microcrystalline cellulose 50-200 parts by weight by 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 Film coated tablets according to claim 1, which is characterized in that according to parts by weight, the Mei Suoshu
The Core formulation composition of sharp Film coated tablets is selected from one of following：
50 parts by weight of Mei Suoshuli by micronization processes, 170 parts by weight of microcrystalline cellulose by micronization processes gather dimension
8 parts by weight of ketone K30, the crospovidone that the crospovidone and outer addition that interior addition adds in add in totally 12 parts by weight, stearic acid
2.5 parts by weight of magnesium；
50 parts by weight of Mei Suoshuli by micronization processes, 150 parts by weight of microcrystalline cellulose by micronization processes gather dimension
8 parts by weight of ketone K30, the crospovidone that the crospovidone and outer addition that interior addition adds in add in totally 12 parts by weight, stearic acid
2.4 parts by weight of magnesium；
50 parts by weight of Mei Suoshuli by micronization processes, 120 parts by weight of microcrystalline cellulose by micronization processes gather dimension
10 parts by weight of ketone K30, the crospovidone that the crospovidone and outer addition that interior addition adds in add in totally 5 parts by weight, stearic acid
1 parts by weight of magnesium；
25 parts by weight of Mei Suoshuli by micronization processes, 200 parts by weight of microcrystalline cellulose by micronization processes gather dimension
6 parts by weight of ketone K30, the crospovidone that the crospovidone and outer addition that interior addition adds in add in totally 16 parts by weight, stearic acid
0.8 parts by weight of magnesium；
75 parts by weight of Mei Suoshuli by micronization processes, 150 parts by weight of microcrystalline cellulose by micronization processes gather dimension
12 parts by weight of ketone K30, the crospovidone that the crospovidone and outer addition that interior addition adds in add in totally 20 parts by weight are stearic
Sour 4 parts by weight of magnesium；
100 parts by weight of Mei Suoshuli by micronization processes, 120 parts by weight of microcrystalline cellulose by micronization processes are gathered
7 parts by weight of ketone K30 are tieed up, the crospovidone that the crospovidone and outer addition that interior addition adds in add in totally 12 parts by weight are stearic
Sour 2.5 parts by weight of magnesium；
100 parts by weight of Mei Suoshuli by micronization processes, 120 parts by weight of microcrystalline cellulose by micronization processes are gathered
10 parts by weight of ketone K30 are tieed up, the crospovidone that the crospovidone and outer addition that interior addition adds in add in totally 14 parts by weight, firmly
3 parts by weight of fatty acid magnesium；
125 parts by weight of Mei Suoshuli by micronization processes, 90 parts by weight of microcrystalline cellulose by micronization processes gather dimension
7 parts by weight of ketone K30, the crospovidone that the crospovidone and outer addition that interior addition adds in add in totally 10 parts by weight, stearic acid
2 parts by weight of magnesium.
A kind of 3. method of Mei Suoshuli Film coated tablets prepared described in claims 1 or 2, which is characterized in that including：
(1) Mei Suoshuli and microcrystalline cellulose 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, after crospovidone, PVP K30 and magnesium stearate are crushed respectively
80 mesh sieve is crossed, 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 Film coated tablets.
4. according to the method described in claim 3, it is characterized in that, further comprise：
The Mei Suoshuli Film coated tablets is 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, the parameter of the Cotton seeds is as follows：Average inlet air temperature
It it 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, average material
3~4g/min of flow velocity.
7. according to the method described in claim 3, it is characterised in that it includes：
(1) Mei Suoshuli with microcrystalline cellulose is mixed, and obtained mixture is subjected to micronization processes, to obtain grain
Diameter is 5 microns to 100 microns of the mixture micro powder granule, and crospovidone, PVP K30 and magnesium stearate are distinguished powder
80 mesh sieve is crossed after broken, 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 Film coated 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 Film coated tablets is packed using polyvinyl chloride bubble-cap and two-sided composite aluminium film bag.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410438406.8A CN105434388B (en) | 2014-08-29 | 2014-08-29 | Mei Suoshuli Film coated tablets |
| PCT/CN2014/085784 WO2016029495A1 (en) | 2014-08-29 | 2014-09-02 | 4-methoxynimesulide thin film coated tablets |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410438406.8A CN105434388B (en) | 2014-08-29 | 2014-08-29 | Mei Suoshuli Film coated tablets |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105434388A CN105434388A (en) | 2016-03-30 |
| CN105434388B true CN105434388B (en) | 2018-06-19 |
Family
ID=55398693
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410438406.8A Expired - Fee Related CN105434388B (en) | 2014-08-29 | 2014-08-29 | Mei Suoshuli Film coated tablets |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN105434388B (en) |
| WO (1) | WO2016029495A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1511828A (en) * | 2002-12-31 | 2004-07-14 | �й������ž�����ҽѧ��ѧԺ����ҽ | Sufonic aniline derivatives and their medicinal use |
| CN101431992A (en) * | 2006-04-24 | 2009-05-13 | 万能药生物有限公司 | Novel low dose pharmaceutical compositions comprising nimesulide, preparation and use thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3840597A (en) * | 1971-02-24 | 1974-10-08 | Riker Laboratories Inc | Substituted 2-phenoxy alkane-sulfonanilides |
| CN103054872B (en) * | 2013-01-24 | 2014-06-04 | 宁夏康亚药业有限公司 | Meloxicam pharmaceutical composition and preparation method thereof |
| CN103553984B (en) * | 2013-03-14 | 2015-11-25 | 湖北生物医药产业技术研究院有限公司 | Mei Suoshuli crystal formation and preparation method thereof |
-
2014
- 2014-08-29 CN CN201410438406.8A patent/CN105434388B/en not_active Expired - Fee Related
- 2014-09-02 WO PCT/CN2014/085784 patent/WO2016029495A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1511828A (en) * | 2002-12-31 | 2004-07-14 | �й������ž�����ҽѧ��ѧԺ����ҽ | Sufonic aniline derivatives and their medicinal use |
| EP1586557A1 (en) * | 2002-12-31 | 2005-10-19 | Institute of Radiation Medicine, Academy of Military Medical Sciences Pla | 4-nitro-2- (4 -methoxy)-phenoxy -methanesulfonanilide derivates and their pharmaceutical use |
| CN101431992A (en) * | 2006-04-24 | 2009-05-13 | 万能药生物有限公司 | Novel low dose pharmaceutical compositions comprising nimesulide, preparation and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| A total synthesis of 4-hydroxynimesulide;Parmjeet Singh，et al;《Indian Journal of Chemistry》;20040630;第43B卷;1263-1264 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016029495A1 (en) | 2016-03-03 |
| CN105434388A (en) | 2016-03-30 |
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