CN106389373B - A kind of xylene monosulfonic acid Lapatinib tablet and preparation method thereof - Google Patents
A kind of xylene monosulfonic acid Lapatinib tablet and preparation method thereof Download PDFInfo
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Abstract
The present invention provides a kind of xylene monosulfonic acid Lapatinib tablets, are prepared by the bulk pharmaceutical chemicals xylene monosulfonic acid Lapatinib and auxiliary material colloidal silicon dioxide that match containing following weight: 45~60 parts of active constituent, 0.25~2 part of colloidal silicon dioxide.The present invention also provides the preparation methods of the tablet.The formulation and technology of Tablets, strong operability, midbody particle good fluidity, tablet weight variation are stablized, and compressibility is strong, and compared with former triturate, the In Vitro Dissolution feature under different medium is consistent with stability test；Preliminary pharmacological testing has been carried out simultaneously, and drug effect and original are ground unanimously.
Description
Technical field
The present invention relates to a kind of xylene monosulfonic acid Lapatinib tablets, belong to field of pharmaceutical preparations.
Background technique
N- { the chloro- 4- of 3- [(3- chlorobenzyl) oxygroup] phenyl } -6- [5- ({ [2- (mesyl) ethyl] amino } methyl) -
2- furyl] -4- quinazoline amine xylenesulfonate monohydrate, also known as one hydration xylene monosulfonic acid Lapatinib, as one
The 4- quinazoline of kind protein tyrosine kinase EGFR (EGF-R ELISA-abbreviation erbB-1) and erbB-2 double inhibitor
Amine compounds were published in patent (WO02/02552) on 01 10th, 2002.Being proved to the compound simultaneously can be used for controlling
Treat various cancers, including breast cancer, lung cancer, bladder cancer, head-neck carcinoma and gastric cancer.The compound is within the scope of physiology correlation pH
Soluble special poor, specification is larger simultaneously for difference special for this dissolubility, drug of poor fluidity, using routine preparation process not
High Dissolution behaviours and good flow behavior [CN200680021941.7, pharmaceutical composition] required for capable of obtaining.Original is developed
Agent patent (CN200680021941.7) is by using fluidized bed granulation technology, using microcrystalline cellulose as filler, PVP K30
Wetting agent, carboxyrnethyl starch sodium for fluidized bed prilling are additional disintegrating agent, the preparation process that magnesium stearate is lubricant, in technique
In the process, it can preferably guarantee the mobility of material, the dissolution rate of tablet is also higher, can reach acceptable biology benefit
Expenditure.The prescription proportion listed in its Central Plains triturate patent is as follows:
Although above-mentioned patent solves the problems, such as material fluidity using fluidization, particle is loose, final dissolution rate compared with
Height, but still have very big problem.It finds during the test, N- { the chloro- 4- of 3- [(3- chlorobenzyl) oxygroup] phenyl } -6-
[5- ({ [2- (mesyl) ethyl] amino } methyl) -2- furyl] -4- quinazoline amine xylenesulfonate monohydrate is viscous
Property it is strong, dissolubility is poor, reaches higher bioavilability and needs to carry out stringent granularity control.Generally for the type drug,
Need to carry out micronization processes, but this compound granularity is meticulous when will lead to stripping analysis that sample flocculates, and is unfavorable for product
Final dissolution, therefore only need to control active constituent in certain particle size range.The too big material of viscosity directly carries out simultaneously
Micronization processes or shaking screen sieving processing are not allowed easy to operate, therefore develop suitable active constituent size controlling method and are
The critical issue of the smooth industrialized production of this product, however original grinds patent and does not give specific solution.
Therefore a kind of mature and stable xylene monosulfonic acid Lapatinib tablet is developed, Chinese pharmaceutical enterprises are widely popularized
Have great importance.
Summary of the invention
In order to solve the above-mentioned technical problems, the present invention provides a kind of xylene monosulfonic acid Lapatinib tablets.The present invention is another
There is provided the preparation methods of the tablet for one technical solution.
The present invention provides a kind of xylene monosulfonic acid Lapatinib tablets, it contains bulk pharmaceutical chemicals xylene monosulfonic acid Lapatinib
It is prepared with auxiliary material colloidal silicon dioxide, weight proportion are as follows:
45~60 parts of xylene monosulfonic acid Lapatinib, 0.25~2 part of colloidal silicon dioxide.
It is further preferred that the weight proportion of the bulk pharmaceutical chemicals and colloidal silicon dioxide are as follows:
45~60 parts of xylene monosulfonic acid Lapatinib, 0.5~1.5 part of colloidal silicon dioxide.
It is further preferred that the weight proportion of the bulk pharmaceutical chemicals and colloidal silicon dioxide are as follows:
45~60 parts of xylene monosulfonic acid Lapatinib, 0.8~1.2 part of colloidal silicon dioxide.
Colloidal silicon dioxide in the amount ranges is added, and facilitates the dispersion dissolution of drug, to guarantee development
With the bioequivalence of former triturate.
Wherein, the auxiliary material further includes mannitol, microcrystalline cellulose, disintegrating agent, adhesive, lubricant, coating premix
Agent, weight proportion are as follows:
10~30 parts of mannitol, 15~35 parts of microcrystalline cellulose, 1~8 part of disintegrating agent, 1.5~6 parts of adhesive, lubricant
0.3~1.8 part, 0.5~6 part of pre-mixing agent of coating.
Wherein, the disintegrating agent be croscarmellose sodium or carboxyrnethyl starch sodium, adhesive be PVP K30 or
Hydroxypropyl methylcellulose；The lubricant is sodium stearyl fumarate, magnesium stearate, stearic acid, talcum powder；The tablet be by
The bulk pharmaceutical chemicals and auxiliary material of following weight proportion are prepared:
45~54 parts of xylene monosulfonic acid Lapatinib, 0.5~1.5 part of colloidal silicon dioxide, 15-25 parts of mannitol, crystallite
20~30 parts of cellulose, 2~6 parts of croscarmellose sodium, 2.5~3.5 parts of hydroxypropyl methylcellulose, magnesium stearate 0.8~
1.5 parts, 1~6 part of pre-mixing agent of coating.
It is further preferred that it is prepared by the bulk pharmaceutical chemicals and auxiliary material of following weight proportion: xylene monosulfonic acid draws pa
For 45~54 parts of Buddhist nun, 0.8~1.2 part of colloidal silicon dioxide, 15~20 parts of mannitol, 22~26 parts of microcrystalline cellulose, crosslinking carboxylic
2~4 parts of sodium carboxymethylcellulose pyce, 2.5~3.5 parts of hydroxypropyl methylcellulose, 0.8~1.5 part of magnesium stearate, coating pre-mixing agent 1~4
Part；
It is further preferred that it is prepared by the bulk pharmaceutical chemicals and auxiliary material of following weight proportion:
49~50 parts of xylene monosulfonic acid Lapatinib, 0.9~1 part of colloidal silicon dioxide, 18~19 parts of mannitol, crystallite are fine
Tie up plain 24~25 parts, 2~3 parts of croscarmellose sodium, 3~3.5 parts of hydroxypropyl methylcellulose, magnesium stearate 0.8~1.2
Part, 1~3 part of pre-mixing agent of coating；The coating pre-mixing agent is Opadry 17B620000.
Wherein, 50% partial size is lower than 100 μm in the mannitol, and 90% partial size is lower than 250 μm, using such partial size
After can preferably guarantee to be sufficiently mixed with active constituent, while to large dosage insoluble drug play preferably dispersion make
With；50% partial size is lower than 150 μm in the microcrystalline cellulose, and 90% partial size is lower than 250 μm；The microcrystalline cellulose model is
Microcrystalline cellulose pH101, it is highly preferred that the microcrystalline cellulose model is microcrystalline cellulose KG802.Cross-linked carboxymethyl fiber
The dosage of plain sodium, a certain range of dosage increase, it is ensured that tablet preferably dissolves out, but is more than a certain range, dosage
It is bigger, more it is unfavorable for final dissolution.The hydroxypropyl methylcellulose is preferably hydroxypropyl methylcellulose E5, and suitable adhesive is molten
Degree and dosage can guarantee the more preferable dissolution of this product.
The present invention provides a kind of preparation methods for preparing the tablet, it includes the following steps:
1) xylene monosulfonic acid Lapatinib and colloidal silicon dioxide are crossed to the processing of 40~80 mesh screens respectively, weigh recipe quantity
Then mixing crosses the processing of 100~200 meshes, and the two is uniformly mixed；
2) microcrystalline cellulose, mannitol respectively cross 80~100 meshes, then by microcrystalline cellulose, mannitol, disintegrating agent and
Adhesive weighs respectively and according to quantity in the mixture that is added in step 1), then mixes under bulk drug of pretreatment adds with interior granulator, mixes
Even revolving speed preferably 200~400rpm, cutter rotating velocity preferably 200~800rpm；
3) softwood preparation being carried out to above-mentioned mixing powder with purified water, during softwood processed, speed of agitator is 200~
400rpm, cutter rotating velocity are 300~1200rpm；The sieve mesh number of granulation is 16~30 mesh；
4) particle of preparation is dried, drying temperature is 50~60 DEG C, drying moisture to 1.0~3.5%, drying
Whole grain mesh number preferably 20~30 mesh of grain；
5) into step 4), lubricant, mixing is added in gained particle, and incorporation time is 5~10min；
6) it is coated, obtains tablet.
The colloidal silicon dioxide has stronger hydrophilicity, and before use, colloidal silicon dioxide needs by 40~
The processing of 80 mesh screens, then mix with active constituent, the viscosity for improving active constituent is big, electrostatic by force, poor fluidity the disadvantages of,
Simultaneously for the pretreatment of active constituent, play the role of highly significant to the size controlling of active constituent.Simultaneously using appropriate
Microcrystalline cellulose and mannitol can improve the conglomeration accumulation situation of big specification insoluble drug In Vitro Dissolution test, utilize
Super-disintegrant croscarmellose sodium and high-hydrophilic adhesive hydroxypropyl methylcellulose are conducive to insoluble drug most
Dissolution eventually.Mature preparation process of the present invention is stablized, and can guarantee the stability of different batches, is suitble to the current country
Pharmaceutical industries metaplasia produces.
By above-mentioned specific preparation prescription, inventor has found this tablet by aforesaid operations, and strong operability is final
Mobility of particle is good, and tablet weight variation is stablized, and compressibility is strong.In Vitro Dissolution of the final tablet and former triturate under different medium
Situation is consistent with stability test；Preliminary pharmacological testing is carried out simultaneously, and drug effect and original are ground unanimously.
Detailed description of the invention
The dissolution curve of the tablet of Fig. 1 embodiment 1 and former triturate in+0.5% Tween medium of pH1.0 hydrochloric acid
The dissolution curve of the tablet of Fig. 2 embodiment 1 and former triturate in+0.5% Tween medium of pH4.5 acetate buffer solution
The dissolution curve of the tablet of Fig. 3 embodiment 1 and former triturate in+1.0% Tween medium of purified water
The dissolution curve of the tablet of Fig. 4 embodiment 1 and former triturate in pH6.8+2.0% Tween medium
The dissolution of the tablet of Fig. 5 comparative example 1 and comparative example 2 and former triturate in+0.5% Tween medium of pH1.0 hydrochloric acid
Curve
The dissolution curve of the tablet of Fig. 6 comparative example 1 and comparative example 2 and former triturate in pH6.8+2.0% Tween medium
Specific embodiment
In order to better illustrate the present invention and its acquired effect, it is done furtherly below in conjunction with specific embodiment
It is bright, but the scope of the present invention is not limited to the concrete scheme of embodiment.
The preparation of the xylene monosulfonic acid Lapatinib tablet of the present invention of embodiment 1
Xylene monosulfonic acid Lapatinib tablet of the invention, the ingredient including following weight proportion:
Preparation: conventional tablet pharmaceutical equipment production can be used in the dosage form, specifically the preparation method is as follows: by bulk pharmaceutical chemicals diformazan
Benzene sulfonic acid Lapatinib and colloidal silicon dioxide tentatively mix, and are uniformly mixed after sieving with 100 mesh sieve processing.Microcrystalline cellulose and sweet dew
Alcohol sieves with 100 mesh sieve respectively, then weighs respectively according to quantity with croscarmellose sodium, hydroxypropyl methylcellulose, and in order according to
It is secondary to be added in above-mentioned mixture, it is mixed under bulk drug of pretreatment adds with interior granulator, mixing revolving speed is 300rpm, and cutter rotating velocity is
500rpm；Then purified water is added and prepares softwood, during softwood processed, speed of agitator 300rpm, cutter rotating velocity 1200rpm,
It is dried to moisture 2% or so under the conditions of 55 DEG C after the granulation of 24 meshes, the stearic acid of recipe quantity is added after 24 mesh sieves
Magnesium mix, carry out intermediates content detection, determine tabletting after slice weight, with Opadry 17B620000 aqueous solution to gained label into
Row coating, obtains tablet, specification 0.25g/ piece.
Tablet and former triturate (Britain's GlaxoSmithKline PLC company, trade name prepared by embodiment 1) together
Carry out Dissolution Rate Testing.Dissolution Rate Testing method dissolves out database recommended method with reference to FDA, and compares together with former triturate
The In Vitro Dissolution situations of four kinds of different mediums.Dissolving-out method used is paddle method, 55rpm, and dissolution medium is respectively 900ml's
+ 0.5% tween of pH1.0 hydrochloric acid solution ,+0.5% tween of pH4.5 acetate buffer solution ,+2% tween of pH6.8 phosphate buffer and pure
Change+2% tween of water.The dissolution medium of different pH is the dissolution of different medium for the physiological environment of different parts in analogue body
Property comparison can reflect the quality conformance with former triturate to a certain extent.As a result as shown in figures 1-4, embodiment 1
Tablet and former triturate are consistent in the dissolution characteristic of different medium.
Three batches of samples are continuously prepared with the formulation and technology of above-described embodiment, the In Vitro Dissolution curve of prepared tablet keeps one
It causes (Fig. 1~4), while by the tablet of embodiment 1 and xylene monosulfonic acid Lapatinib piece (former triturate, 0.25g/ piece, Britain Pueraria lobota
The SmithKline Lan Su company) progress influence factor and long-term stable experiment are synchronized, investigate the keys such as content, related substance, dissolution rate
The variation of qualitative attribute, testing result is as shown in the following table 1,2.As can be seen that the tablet stability of embodiment 1 is good, it is relatively former
Triturate, or even there is better stability.
The tablet and original triturate (specification: 0.25g/ piece, Britain's Ge Lansu history of the embodiment of the present invention 1 have also been investigated simultaneously
Gram company) in the intracorporal relative bioavailability of beasle dog.Two kinds of Beagle dog different dimethylbenzene sulphurs are given by single oral
Sour Lapatinib preparation, in different time points acquisition blood sample in, LC-MS/MS measurement administration after Lapatinib blood concentration simultaneously
Relevant pharmacokinetic parameter is calculated, the result of acquisition such as the following table 1:
1 Beagle dog single oral of table gives internal pharmacokinetic results after 1 tablet of embodiment or former triturate
By experimental result as can be seen that beasle dog gives the tablet of embodiment 1 with after former triturate, plasma concentration reaches peak
Time is in 8.0h or so；80~125% ranges of 90% credibility interval of the AUC of the tablet of embodiment 1 in former triturate AUC
It is interior；Simultaneously through paired t-test, the pharmacokinetic parameters of Lapatinib piece are in no difference of science of statistics (P between by test preparation and former triturate
>0.05).It to sum up can determine whether, the tablet of embodiment 1 and former triturate bioequivalence.
The preparation of the xylene monosulfonic acid Lapatinib tablet of the present invention of embodiment 2
Xylene monosulfonic acid Lapatinib tablet of the invention, the ingredient including following weight proportion:
Preparation: conventional tablet pharmaceutical equipment production can be used in the dosage form, specifically the preparation method is as follows: by bulk pharmaceutical chemicals diformazan
Benzene sulfonic acid Lapatinib and colloidal silicon dioxide cross the processing of 150 meshes, are uniformly mixed.Microcrystalline cellulose and mannitol mistake respectively
Then 100 meshes are added sequentially in above-mentioned mixture in order according to quantity with croscarmellose sodium, hydroxypropylcellulose
It mixes, is mixed under bulk drug of pretreatment adds with interior granulator, mixing revolving speed is 200rpm, cutter rotating velocity 600rpm；Then purifying is added
Water prepares softwood, during softwood processed, speed of agitator 400rpm, cutter rotating velocity 1000rpm, in 50 DEG C of items after the granulation of 20 meshes
Moisture 2% or so is dried under part, the sodium stearyl fumarate that recipe quantity is added after 24 mesh sieves mixes, and carries out intermediate
Content detection determines tabletting after slice weight, is coated with Opadry 17B620000 aqueous solution to gained label, coating weight gain
2%, tablet, specification 0.25g/ piece are obtained, final coating tablet is packed in vinyon bottle.
The preparation of the xylene monosulfonic acid Lapatinib tablet of the present invention of embodiment 3
Xylene monosulfonic acid Lapatinib tablet of the invention, the ingredient including following weight proportion:
Preparation: conventional tablet pharmaceutical equipment production can be used in the dosage form, specifically the preparation method is as follows: by bulk pharmaceutical chemicals diformazan
Benzene sulfonic acid Lapatinib and colloidal silicon dioxide cross the processing of 200 meshes, are uniformly mixed.Microcrystalline cellulose KG802 and mannitol point
80 meshes are not crossed, are then added sequentially to above-mentioned mixture in order with croscarmellose sodium, hydroxypropyl methylcellulose
It is mixed under bulk drug of pretreatment adds with interior granulator, mixes revolving speed 400rpm, cutter rotating velocity 600rpm；Then addition purified water is prepared soft
It is left to be dried to moisture 2% after the granulation of 16 meshes under the conditions of 50 DEG C by material, speed of agitator 400rpm, cutter rotating velocity 800rpm
The right side, the magnesium stearate that recipe quantity is added after 24 mesh sieves mix, carry out intermediates content detection, press after determining slice weight
Piece is coated gained label with Opadry 17B620000 aqueous solution, coating weight gain 3%, obtains tablet, specification 0.25g/ piece,
Final coating tablet is packed in vinyon bottle.
The preparation of the xylene monosulfonic acid Lapatinib tablet of the present invention of embodiment 4
Xylene monosulfonic acid Lapatinib tablet of the invention, the ingredient including following weight proportion:
Preparation: conventional tablet pharmaceutical equipment production can be used in the dosage form, specifically the preparation method is as follows: by bulk pharmaceutical chemicals diformazan
Benzene sulfonic acid Lapatinib and colloidal silicon dioxide cross the processing of 200 meshes, are uniformly mixed.Microcrystalline cellulose and mannitol mistake respectively
Then 100 meshes are added sequentially in above-mentioned mixture in order according to quantity with croscarmellose sodium, PVP K30
It is mixed under bulk drug of pretreatment adds with interior granulator, mixes revolving speed 400rpm, the preferred 600rpm of cutter rotating velocity；Then purified water preparation is added
Softwood, speed of agitator 400rpm, cutter rotating velocity 600rpm；Moisture 2% is dried under the conditions of 55 DEG C after the granulation of 24 meshes
Left and right, the magnesium stearate that recipe quantity is added after 24 mesh sieves mix, carry out intermediates content detection, press after determining slice weight
Piece is coated gained label with Opadry 17B620000 aqueous solution, coating weight gain 2%, obtains tablet, specification 0.25g/ piece,
Final coating tablet is packed in vinyon bottle.
Test proves that embodiment 2-4 has and the equivalent experiment effect of embodiment 1.
The test of the xylene monosulfonic acid Lapatinib additive of tablet comparative selection of the present invention of embodiment 5
Inventor saves the partial supplementary material such as colloidal silicon dioxide in xylene monosulfonic acid Lapatinib tablet of the present invention, and
The dosage for adjusting other auxiliary materials is prepared into comparative example 1 and comparative example 2；And grind medicine with original and compare, specific test is as follows:
Comparative example 1
A kind of xylene monosulfonic acid Lapatinib tablet, the ingredient including following weight proportion:
Preparation: conventional tablet pharmaceutical equipment production can be used in the dosage form, specifically the preparation method is as follows: by bulk pharmaceutical chemicals diformazan
Benzene sulfonic acid Lapatinib crosses the processing of 200 meshes.Then and cross-linked carboxymethyl microcrystalline cellulose and mannitol sieve with 100 mesh sieve respectively,
Sodium cellulosate, hydroxypropyl methylcellulose are weighed respectively by recipe quantity, and are added sequentially to mix in above-mentioned bulk pharmaceutical chemicals in order, so
Purified water is added afterwards and prepares softwood, speed of agitator 300rpm, cutter rotating velocity 1200rpm, in 55 DEG C of items after the granulation of 20 meshes
Moisture 2% or so is dried under part, the magnesium stearate that recipe quantity is added after 24 mesh sieves mixes, and carries out intermediates content
Detection, determine after slice weight tabletting to get.Gained label is coated with Opadry 17B620000 aqueous solution, coating weight gain
3%, tablet, specification 0.25g/ piece are obtained, final coating tablet is packed in vinyon bottle.
Comparative example 2
A kind of xylene monosulfonic acid Lapatinib tablet, the ingredient including following weight proportion:
Preparation: conventional tablet pharmaceutical equipment production can be used in the dosage form, specifically the preparation method is as follows: by bulk pharmaceutical chemicals diformazan
Benzene sulfonic acid Lapatinib crosses the processing of 150 meshes.Then and cross-linked carboxymethyl microcrystalline cellulose and mannitol sieve with 100 mesh sieve respectively,
Sodium cellulosate, hydroxypropyl methylcellulose weigh respectively according to quantity, and are added sequentially to mix in bulk pharmaceutical chemicals in order, mix revolving speed
200rpm, cutter rotating velocity 400rpm；Then purified water is added and prepares softwood, speed of agitator 400rpm, cutter rotating velocity is
800rpm.It is dried to moisture 2% or so under the conditions of 50 DEG C after the granulation of 20 meshes, recipe quantity is added after 24 mesh sieves
Sodium stearyl fumarate mixes, and carries out intermediates content detection, tabletting after slice weight is determined, with Opadry 17B620000 aqueous solution pair
Gained label is coated, coating weight gain 2%, obtains tablet, specification 0.25g/ piece, final coating tablet in vinyon bottle into
Row packaging.
Tablet (specification: 0.25g/ piece) prepared by comparative example 1 and comparative example 2 and former triturate (specification: 0.25g/ piece,
Britain's GlaxoSmithKline PLC company, trade name) Dissolution Rate Testing is carried out together.Dissolution Rate Testing method is molten with reference to FDA
Database recommended method out, dissolving-out method used be paddle method, 55rpm, dissolution medium be respectively 900ml pH1.0 hydrochloric acid solution+
0.5% tween ,+2% tween of pH6.8 phosphate buffer.The dissolution medium of different pH is for the life of different parts in analogue body
Environment is managed, the dissolution characteristic of different medium can relatively reflect the quality conformance with former triturate to a certain extent.(see figure
5, Fig. 6)
Show comparative example 1, the sample of comparative example 2 and former triturate in pH1.0 hydrochloric acid and pH6.8 by above-mentioned test result
Dissolution curve under phosphate buffer differs greatly, and final dissolution rate is significantly lower than former triturate.
Claims (13)
1. a kind of xylene monosulfonic acid Lapatinib tablet, it is characterised in that: by the bulk pharmaceutical chemicals dimethylbenzene matched containing following weight
Sulfonic acid Lapatinib and auxiliary material colloidal silicon dioxide are prepared:
45~60 parts of xylene monosulfonic acid Lapatinib, 0.25~2 part of colloidal silicon dioxide, 10~30 parts of mannitol, microcrystalline cellulose
15~35 parts of element, 1~8 part of disintegrating agent, 1.5~6 parts of adhesive, 0.3~1.8 part of lubricant, 0.5~6 part of pre-mixing agent of coating；
The preparation method of the tablet the following steps are included:
1) xylene monosulfonic acid Lapatinib and colloidal silicon dioxide are crossed to the processing of 40~80 mesh screens respectively, it is mixed to weigh recipe quantity
It closes, then crosses the processing of 100~200 meshes, and the two is uniformly mixed；
2) microcrystalline cellulose, mannitol cross 60~100 meshes respectively, then by microcrystalline cellulose, mannitol, disintegrating agent and bonding
Agent weighs respectively and according to quantity in the mixture that is added in step 1), is then uniformly mixed under bulk drug of pretreatment adds with interior granulator；
3) softwood preparation carried out to above-mentioned mixing powder with purified water, during softwood processed, speed of agitator is 200~400rpm, is cut
Swivel speed is 300~1200rpm；The sieve mesh number of granulation is 16~30 mesh；
4) particle of preparation is dried, drying temperature is 50~60 DEG C, drying moisture to 1.0~3.5%；
5) into step 4), lubricant, mixing is added in gained particle, and incorporation time is 5~10min；
6) it is coated with coating pre-mixing agent, obtains tablet.
2. tablet according to claim 1, it is characterised in that: the weight of the bulk pharmaceutical chemicals and auxiliary material colloidal silicon dioxide
Proportion are as follows:
45~60 parts of xylene monosulfonic acid Lapatinib, 0.5~1.5 part of colloidal silicon dioxide.
3. tablet according to claim 1, it is characterised in that:
The disintegrating agent is carboxyrnethyl starch sodium, one or two mix in croscarmellose sodium；Adhesive is hydroxypropyl
Methylcellulose, PVP K30, mixing one or more kinds of in hydroxypropylcellulose；The lubricant is stearyl fumarate
The mixing of one or more of sodium, magnesium stearate, stearic acid, talcum powder.
4. tablet according to claim 3, it is characterised in that: the tablet is by the raw material and auxiliary of following weight proportion
Material is prepared:
45~54 parts of xylene monosulfonic acid Lapatinib, 0.5~1.5 part of colloidal silicon dioxide, 15~25 parts of mannitol, microcrystalline cellulose
Plain 20~30 parts, 2~6 parts of croscarmellose sodium, 2.5~3.5 parts of hydroxypropyl methylcellulose, magnesium stearate 0.8~1.5
Part, 1~6 part of pre-mixing agent of coating.
5. tablet according to claim 4, it is characterised in that: it is the bulk pharmaceutical chemicals and auxiliary material preparation by following weight proportion
It forms:
45~54 parts of xylene monosulfonic acid Lapatinib, 0.8~1.2 part of colloidal silicon dioxide, 15~20 parts of mannitol, microcrystalline cellulose
Plain 22~26 parts, 2~4 parts of croscarmellose sodium, 2.5~3.5 parts of hydroxypropyl methylcellulose, magnesium stearate 0.8~1.5
Part, 1~4 part of pre-mixing agent of coating；The coating pre-mixing agent is Opadry 17B620000.
6. tablet according to claim 5, it is characterised in that: it is the bulk pharmaceutical chemicals and auxiliary material preparation by following weight proportion
It forms:
49~50 parts of xylene monosulfonic acid Lapatinib, 0.9~1 part of colloidal silicon dioxide, 18~19 parts of mannitol, microcrystalline cellulose
24~25 parts, 2~3 parts of croscarmellose sodium, 3~3.5 parts of hydroxypropyl methylcellulose, 0.8~1.2 part of magnesium stearate, packet
1~3 part of clothing pre-mixing agent；The coating pre-mixing agent is Opadry 17B620000.
7. tablet described in claim 1~6 any one, it is characterised in that: 50% partial size is lower than 100 in the mannitol
μm, 90% partial size is lower than 250 μm.
8. tablet described in claim 1~6 any one, it is characterised in that: 50% partial size is low in the microcrystalline cellulose
In 150 μm, 90% partial size is lower than 250 μm.
9. tablet described in claim 1~6 any one, it is characterised in that: the microcrystalline cellulose model is microcrystalline cellulose
Plain pH101 or KG802.
10. a kind of method for preparing tablet described in any one of claim 1 to 9,1) it includes the following steps: dimethylbenzene
Sulfonic acid Lapatinib and colloidal silicon dioxide cross the processing of 40~80 mesh screens respectively, weigh recipe quantity mixing, then cross 100~
The processing of 200 meshes, and the two is uniformly mixed；
2) microcrystalline cellulose, mannitol cross 60~100 meshes respectively, then by microcrystalline cellulose, mannitol, disintegrating agent and bonding
Agent weighs respectively and according to quantity in the mixture that is added in step 1), is then uniformly mixed under bulk drug of pretreatment adds with interior granulator；
3) softwood preparation carried out to above-mentioned mixing powder with purified water, during softwood processed, speed of agitator is 200~400rpm, is cut
Swivel speed is 300~1200rpm；The sieve mesh number of granulation is 16~30 mesh；
4) particle of preparation is dried, drying temperature is 50~60 DEG C, drying moisture to 1.0~3.5%；
5) into step 4), lubricant, mixing is added in gained particle, and incorporation time is 5~10min；
6) it is coated with coating pre-mixing agent, obtains tablet.
11. method described in any one of claim 10, it is characterised in that:
The speed of agitator 2) being uniformly mixed under step bulk drug of pretreatment adds with interior granulator is 200~400rpm.
12. method described in any one of claim 10, it is characterised in that:
The cutter rotating velocity 2) being uniformly mixed under step bulk drug of pretreatment adds with interior granulator is 200~800rpm.
13. method described in any one of claim 10, it is characterised in that:
The whole grain mesh number of the 3) step drying particle is 16~24 mesh.
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| CN101203211A (en) * | 2005-04-19 | 2008-06-18 | 史密丝克莱恩比彻姆（科克）有限公司 | Pharmaceutical composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101203211A (en) * | 2005-04-19 | 2008-06-18 | 史密丝克莱恩比彻姆（科克）有限公司 | Pharmaceutical composition |
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| CN106389373A (en) | 2017-02-15 |
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