CN106389373A - Lapatinib ditosylate tablet and preparation method thereof - Google Patents

Abstract

The present invention provides a lapatinib ditosylate tablet, which is prepared from a bulk drug lapatinib ditosylate and an auxiliary material colloidal silicon dioxide according to a certain weight ratio, wherein the active ingredient is 45-60 parts, and the colloidal silicon dioxide is 0.25-2 parts. The present invention further provides a preparation method of the tablet. According to the present invention, the operability of the process is strong, the fluidity of the intermediate particles is good, the tablet weight difference is stable, the compressibility is strong, and the in vitro dissolution characteristics under different medias and the stability test results of the lapatinib ditosylate tablet of the present invention are consistent with the originally-researched preparation; and the primary pharmacological test results show that the efficacy is consistent with the original research.

Description

A kind of xylene monosulfonic acid Lapatinib tablet and preparation method thereof

Technical field

The present invention relates to a kind of xylene monosulfonic acid Lapatinib tablet, belong to field of pharmaceutical preparations.

Background technology

N- { the chloro- 4- of 3- [(3- chlorobenzyl) epoxide] phenyl } -6- [5- ({ [2- (mesyl) ethyl] amino } first Base) -2- furyl] -4- quinazoline amine xylenesulfonate monohydrate, draws also known as a hydration xylene monosulfonic acid Handkerchief replaces Buddhist nun, as a kind of protein tyrosine kinase EGFR (EGF-R ELISA-abbreviation erbB-1) With the 4- quinazoline amines of erbB-2 double inhibitor, it was published in patent on 01 10th, 2002 (WO02/02552).Be proved to this compound to can be used for treating various cancers simultaneously, including breast carcinoma, Pulmonary carcinoma, bladder cancer, incidence cancer and gastric cancer.Solubility in the range of physiology correlation pH for this compound is special Difference, for this dissolubility special difference larger, poor fluidity the medicine of specification simultaneously, using conventional preparation Technique can not obtain required high Dissolution behaviours and good flow behavior [CN200680021941.7, medicine Compositions].Former triturate patent (CN200680021941.7) is passed through using fluidized bed granulation technology, With Microcrystalline Cellulose as filler, the wetting agent as fluidized bed prilling for the Povidone K 30, carboxymethylstach sodium be Additional disintegrating agent, magnesium stearate are the preparation technology of lubricant, in technical process, can preferably protect The mobility of exhibit material, the dissolution of tablet is also higher, can reach acceptable bioavailability. The prescription proportioning listed in its Central Plains triturate patent is as follows：

Although above-mentioned patent solves Flow of Goods and Materials sex chromosome mosaicism using fluidization, granule is loose, finally Dissolution is higher, but yet suffers from very big problem.Process of the test finds, N- { 3- chloro- 4- [(3- Chlorobenzyl) epoxide] phenyl } -6- [5- ({ [2- (mesyl) ethyl] amino } methyl) -2- furyl] -4- quinoline Oxazoline amine xylenesulfonate monohydrate viscosity is strong, and dissolubility is poor, and reaching higher bioavailability needs Carry out strict Task-size Controlling.Generally for the type medicine, need to carry out micronization processes, but This compound granularity is meticulous to lead to sample flocculation during stripping analysises, be unfavorable for the final dissolution of product, because This only needs to control active component in certain particle size range.The too big material of viscosity is directly carried out simultaneously The process of sieving of micronization processes or shaking screen is not all allowed easy to operate, therefore develops suitable active component grain Footpath control method is the key issue of the smooth industrialized production of this product, however former grind patent do not give bright True solution.

Therefore develop a kind of mature and stable xylene monosulfonic acid Lapatinib tablet, for Chinese pharmaceutical enterprises It is widely popularized and have great importance.

Content of the invention

In order to solve above-mentioned technical problem, the invention provides a kind of xylene monosulfonic acid Lapatinib tablet. Another technical scheme of the present invention there is provided the preparation method of this tablet.

The invention provides a kind of xylene monosulfonic acid Lapatinib tablet, it contains crude drug xylene monosulfonic acid Lapatinib and adjuvant silica sol are prepared from, and its weight proportion is：

45～60 parts of xylene monosulfonic acid Lapatinib, 0.25～2 part of silica sol.

It is further preferred that the weight proportion of described crude drug and silica sol is：

45～60 parts of xylene monosulfonic acid Lapatinib, 0.5～1.5 part of silica sol.

It is further preferred that the weight proportion of described crude drug and silica sol is：

45～60 parts of xylene monosulfonic acid Lapatinib, 0.8～1.2 part of silica sol.

Colloidal silica in this amount ranges adds, and contributes to the dispersion dissolution of medicine, thus ensureing Development and the bioequivalence of former triturate.

Wherein, described adjuvant also includes Mannitol, Microcrystalline Cellulose, disintegrating agent, binding agent, lubrication Agent, coating pre-mixing agent, its weight proportion is：

10～30 parts of Mannitol, 15～35 parts of Microcrystalline Cellulose, 1～8 part of disintegrating agent, binding agent 1.5～6 Part, 0.3～1.8 part of lubricant, 0.5～6 part of coating pre-mixing agent.

Wherein, described disintegrating agent is cross-linking sodium carboxymethyl cellulose or carboxymethylstach sodium, binding agent are poly- Dimension ketone K30 or Hypromellose；Described lubricant is sodium stearyl fumarate, magnesium stearate, Hard Fat Acid, Pulvis Talci；Described tablet is to be prepared from by the crude drug of following weight proportioning and adjuvant：

45～54 parts of xylene monosulfonic acid Lapatinib, 0.5～1.5 part of silica sol, Mannitol 15-25 Part, 20～30 parts of Microcrystalline Cellulose, 2～6 parts of cross-linking sodium carboxymethyl cellulose, Hypromellose 2.5～3.5 Part, 0.8～1.5 part of magnesium stearate, 1～6 part of coating pre-mixing agent.

It is further preferred that it is to be prepared from by the crude drug of following weight proportioning and adjuvant：Dimethylbenzene 45～54 parts of sulfonic acid Lapatinib, 0.8～1.2 part of silica sol, 15～20 parts of Mannitol, crystallite 22～26 parts of cellulose, 2～4 parts of cross-linking sodium carboxymethyl cellulose, 2.5～3.5 parts of Hypromellose, 0.8～1.5 part of magnesium stearate, 1～4 part of coating pre-mixing agent；

It is further preferred that it is to be prepared from by the crude drug of following weight proportioning and adjuvant：

49～50 parts of xylene monosulfonic acid Lapatinib, 0.9～1 part of silica sol, Mannitol 18～19 Part, 24～25 parts of Microcrystalline Cellulose, 2～3 parts of cross-linking sodium carboxymethyl cellulose, Hypromellose 3～3.5 Part, 0.8～1.2 part of magnesium stearate, 1～3 part of coating pre-mixing agent；Described coating pre-mixing agent is OPADRY 17B620000.

Wherein, in described Mannitol, 50% particle diameter is less than 100 μm, and 90% particle diameter is less than 250 μm, adopts With can preferably ensure after such particle diameter to be sufficiently mixed with active component, simultaneously to heavy dose of indissoluble Property medicine plays more preferable peptizaiton；In described Microcrystalline Cellulose, 50% particle diameter is less than 150 μm, and 90% Particle diameter is less than 250 μm；Described Microcrystalline Cellulose model is Microcrystalline Cellulose pH101, it is highly preferred that institute The Microcrystalline Cellulose model stated is Microcrystalline Cellulose KG802.The consumption of cross-linking sodium carboxymethyl cellulose, one Determining consumption in scope increases it is ensured that the more preferable dissolution of tablet, but exceedes certain limit, consumption Bigger, more it is unfavorable for final dissolution.Described Hypromellose is preferably Hypromellose E5, Suitable binding agent solubility and consumption can ensure that the more preferable dissolution of this product.

The invention provides a kind of preparation method preparing described tablet, it comprises the steps：

1) xylene monosulfonic acid Lapatinib and silica sol are crossed 40～80 eye mesh screens respectively to process, claim Take recipe quantity to mix, then cross 100～200 mesh sieves and process, and will the two mix homogeneously；

2) Microcrystalline Cellulose, Mannitol cross 80～100 mesh sieves respectively, then by Microcrystalline Cellulose, manna Alcohol, disintegrating agent and binding agent weigh respectively according to quantity and are added to step 1) in mixture in, then in height Mix under shearing wet granulator, mix rotating speed preferably 200～400rpm, cutter rotating velocity is preferred 200～800rpm；

3), during carrying out soft material preparation, soft material processed with purified water to above-mentioned mixing powder, speed of agitator is 200～400rpm, cutter rotating velocity is 300～1200rpm；The sieve number pelletized is 16～30 mesh；

4) granule of preparation is dried, drying temperature is 50～60 DEG C, drying moisture to 1.0～3.5%, Dry granulate mesh number preferably 20～30 mesh of granule；

5) to step 4) in gained granule add lubricant, mixing, incorporation time be 5～10min；

6) coating, obtains tablet.

Described silica sol has stronger hydrophilicity, and using before, silica sol needs logical Cross 40～80 eye mesh screens to process, then mix with active component, the viscosity improving active component is big, quiet Electricity is strong, poor fluidity the shortcomings of, simultaneously for the pretreatment of active component, the particle diameter control to active component System plays the effect of highly significant.Can be improved this using appropriate Microcrystalline Cellulose and Mannitol big simultaneously The conglomeration of specification insoluble drug In Vitro Dissolution test piles up situation, using super-disintegrant cross-linked carboxymethyl Sodium cellulosate and high-hydrophilic binding agent Hypromellose are conducive to the final dissolution of insoluble drug.This Invent adopted mature preparation process stable, ensure that the stability of different batches, be suitable for current state Interior pharmaceutical industries metaplasia is produced.

By above-mentioned specific preparation prescription, inventor finds this tablet through aforesaid operations, operability By force, final mobility of particle is good, and tablet weight variation is stable, and compressibility is strong.Final tablet and former development In Vitro Dissolution situation under different medium for the agent is consistent with stability test；Carry out preliminary pharmacology examination simultaneously Test, drug effect with former grind consistent.

Brief description

The tablet of Fig. 1 embodiment 1 and dissolution in pH1.0 hydrochloric acid+0.5% Tween medium for the former triturate Curve

The tablet of Fig. 2 embodiment 1 and former triturate are in pH4.5 acetate buffer solution+0.5% Tween medium Stripping curve

The dissolution in purified water+1.0% Tween medium of the tablet of Fig. 3 embodiment 1 and former triturate is bent Line

The tablet of Fig. 4 embodiment 1 and stripping curve in pH6.8+2.0% Tween medium for the former triturate

The tablet of Fig. 5 comparative example 1 and comparative example 2 is situated between in pH1.0 hydrochloric acid+0.5% tween with former triturate Stripping curve in matter

The tablet of Fig. 6 comparative example 1 and comparative example 2 and former triturate are in pH6.8+2.0% Tween medium Stripping curve

Specific embodiment

In order to the present invention and its acquired effect are better described, to do below in conjunction with specific embodiment Further illustrate, but the scope of the present invention is not limited to the concrete scheme of embodiment.

The preparation of embodiment 1 xylene monosulfonic acid Lapatinib tablet of the present invention

The xylene monosulfonic acid Lapatinib tablet of the present invention, including the composition of following weight proportion：

Preparation：This dosage form can be produced using conventional tablet pharmaceutical equipment, and concrete preparation method is as follows：Will Crude drug xylene monosulfonic acid Lapatinib and colloidal silica tentatively mix, and cross after 100 mesh sieves are processed and mix Uniformly.Microcrystalline Cellulose and Mannitol cross 100 mesh sieves, respectively then with cross-linking sodium carboxymethyl cellulose, hydroxyl Third methylcellulose weighs according to quantity respectively, and is added sequentially in order in above-mentioned mixture, in high shear Mix under wet granulator, mixing rotating speed is 300rpm, cutter rotating velocity is 500rpm；It is subsequently adding purification Water prepares soft material, and during soft material processed, speed of agitator is 300rpm, and cutter rotating velocity is 1200rpm, 24 mesh Sieve series grain is dried to moisture 2% about under the conditions of 55 DEG C, adds recipe quantity after 24 mesh sieve granulate Magnesium stearate mixes, and carries out intermediates content detection, determines tabletting after piece weight, uses OPADRY 17B620000 Aqueous solution is coated to gained label, obtains tablet, specification 0.25g/ piece.

The tablet that prepare embodiment 1 and former triturate (Britain's GlaxoSmithKline PLC company, trade name) carry out Dissolution Rate Testing together.Dissolution Rate Testing method is with reference to FDA dissolution data base recommendation side Method, and compare the In Vitro Dissolution situation of four kinds of different mediums together with former triturate.Dissolution side used Method is paddle method, 55rpm, and dissolution medium is respectively pH1.0 hydrochloric acid solution+0.5% tween of 900ml, pH4.5 Acetate buffer solution+0.5% tween, pH6.8 phosphate buffer+2% tween and purified water+2% tween.Different The dissolution medium of pH is the physiological environment in order to simulate internal different parts, the dissolution characteristic ratio of different medium The quality conformance with former triturate relatively can be reflected to a certain extent.Result is as shown in figures 1-4, real The tablet applying example 1 is consistent in the dissolution characteristic of different medium with former triturate.

Prepare three batch samples, the In Vitro Dissolution curve of prepared tablet so that the formulation and technology of above-described embodiment is continuous It is consistent (Fig. 1～4), the tablet of embodiment 1 and xylene monosulfonic acid Lapatinib piece (former are ground simultaneously Preparation, 0.25g/ piece, Britain's GlaxoSmithKline PLC company) synchronization carries out influence factor and long-time stability are tried Test, investigation content, the change about the Key Quality attribute such as material, dissolution, testing result such as table 1 below, Shown in 2.As can be seen that the tablet stability of embodiment 1 is good, relatively former triturate, or even have more Good stability.

Also the tablet of the embodiment of the present invention 1 and former triturate (specification have been investigated simultaneously：0.25g/ piece, English State's GlaxoSmithKline PLC company) relative bioavailability in beasle dog body.Given by single oral The different xylene monosulfonic acid Lapatinib preparation of two kinds of Beagle dog, in different time points collection blood sample, LC-MS/MS measure administration after the blood drug level of Lapatinib calculate relevant pharmacokinetic parameter, obtain The result such as table 1 below obtaining：

Table 1 Beagle dog single oral gives internal pharmacokinetic results after embodiment 1 tablet or former triturate

By experimental result as can be seen that after beasle dog gives tablet and the former triturate of embodiment 1, blood plasma Concentration peak time is all in 8.0h；90% credibility interval of the AUC of the tablet of embodiment 1 is in former development In the range of the 80～125% of agent AUC；Simultaneously through paired t-test, the pharmacokinetic parameters of Lapatinib piece are being subject to No difference of science of statistics (P between test preparation and former triturate>0.05).To sum up can determine whether, the tablet of embodiment 1 With former triturate bioequivalence.

The preparation of embodiment 2 xylene monosulfonic acid Lapatinib tablet of the present invention

The xylene monosulfonic acid Lapatinib tablet of the present invention, including the composition of following weight proportion：

Preparation：This dosage form can be produced using conventional tablet pharmaceutical equipment, and concrete preparation method is as follows：Will Crude drug xylene monosulfonic acid Lapatinib and silica sol are crossed 150 mesh sieves and are processed, mix homogeneously.Crystallite Cellulose and Mannitol cross 100 mesh sieves respectively, then press with cross-linking sodium carboxymethyl cellulose, Hydroxypropyl Cellulose Amount is added sequentially to mix in above-mentioned mixture in order, mixes under bulk drug of pretreatment adds with interior granulator, mixes Even rotating speed is 200rpm, and cutter rotating velocity is 600rpm；It is subsequently adding purified water and prepare soft material, the soft material phase processed Between, speed of agitator is 400rpm, and cutter rotating velocity is 1000rpm, and 20 mesh sieves are pelletized under the conditions of 50 DEG C Dry to moisture 2% about, add the sodium stearyl fumarate of recipe quantity to mix after 24 mesh sieve granulate, enter Row intermediates content detects, determines tabletting after piece weight, with OPADRY 17B620000 aqueous solution to obtained sheet Core is coated, coating weight gain 2%, obtains tablet, specification 0.25g/ piece, final coated tablet is in polyethylene Plastic bottle is packed.

The preparation of embodiment 3 xylene monosulfonic acid Lapatinib tablet of the present invention

The xylene monosulfonic acid Lapatinib tablet of the present invention, including the composition of following weight proportion：

Preparation：This dosage form can be produced using conventional tablet pharmaceutical equipment, and concrete preparation method is as follows：Will Crude drug xylene monosulfonic acid Lapatinib and colloidal silica are crossed 200 mesh sieves and are processed, mix homogeneously.Crystallite Cellulose KG802 and Mannitol cross 80 mesh sieves, respectively then with cross-linking sodium carboxymethyl cellulose, hydroxypropyl first Cellulose is added sequentially to above-mentioned mixture in order and mixes under bulk drug of pretreatment adds with interior granulator, mixes and turns Fast 400rpm, cutter rotating velocity 600rpm；It is subsequently adding purified water and prepares soft material, speed of agitator is 400rpm, Cutter rotating velocity is 800rpm, and 16 mesh sieves are pelletized and dried under the conditions of 50 DEG C to moisture 2% about, pass through The magnesium stearate adding recipe quantity after 24 mesh sieve granulate mixes, and carries out intermediates content detection, determines piece weight Tabletting afterwards, is coated to gained label with OPADRY 17B620000 aqueous solution, and coating weight gain 3% obtains Tablet, specification 0.25g/ piece, final coated tablet is packed in vinyon bottle.

The preparation of embodiment 4 xylene monosulfonic acid Lapatinib tablet of the present invention

The xylene monosulfonic acid Lapatinib tablet of the present invention, including the composition of following weight proportion：

Preparation：This dosage form can be produced using conventional tablet pharmaceutical equipment, and concrete preparation method is as follows：Will Crude drug xylene monosulfonic acid Lapatinib and colloidal silica are crossed 200 mesh sieves and are processed, mix homogeneously.Crystallite Cellulose and Mannitol cross 100 mesh sieves respectively, then press with cross-linking sodium carboxymethyl cellulose, Povidone K 30 Amount is added sequentially to mix under bulk drug of pretreatment adds with interior granulator in above-mentioned mixture in order, mixes rotating speed 400rpm, the preferred 600rpm of cutter rotating velocity；It is subsequently adding purified water and prepares soft material, speed of agitator is 400rpm, cutter rotating velocity is 600rpm；24 mesh sieves are pelletized and are dried under the conditions of 55 DEG C to moisture 2% left side The right side, adds the magnesium stearate of recipe quantity to mix after 24 mesh sieve granulate, carries out intermediates content detection, Determine tabletting after piece weight, with OPADRY 17B620000 aqueous solution, gained label is coated, coating increases Weigh 2%, obtain tablet, specification 0.25g/ piece, final coated tablet is packed in vinyon bottle.

Test proves, embodiment 2-4 has the experiment effect being equal to embodiment 1.

Embodiment 5 xylene monosulfonic acid Lapatinib additive of tablet comparative selection of the present invention is tested

Inventor is by the partial supplementary material such as silica sol in xylene monosulfonic acid Lapatinib tablet of the present invention Save, and adjust the consumption of other adjuvants, be prepared into comparative example 1 and comparative example 2；And enter with the former medicine that grinds Row contrast, concrete test is as follows：

Comparative example 1

A kind of xylene monosulfonic acid Lapatinib tablet, including the composition of following weight proportion：

Preparation：This dosage form can be produced using conventional tablet pharmaceutical equipment, and concrete preparation method is as follows：Will Crude drug xylene monosulfonic acid Lapatinib is crossed 200 mesh sieves and is processed.Microcrystalline Cellulose and Mannitol cross 100 respectively Mesh sieve, is then weighed respectively by recipe quantity with cross-linking sodium carboxymethyl cellulose, Hypromellose, and presses Order is added sequentially to mix in above-mentioned crude drug, is subsequently adding purified water and prepares soft material, speed of agitator For 300rpm, cutter rotating velocity is 1200rpm, and 20 mesh sieves are pelletized and dried to moisture 2% under the conditions of 55 DEG C Left and right, adds the magnesium stearate of recipe quantity to mix after 24 mesh sieve granulate, carries out intermediates content detection, Determine tabletting after piece weight, obtain final product.With OPADRY 17B620000 aqueous solution, gained label is coated, Coating weight gain 3%, obtains tablet, specification 0.25g/ piece, final coated tablet is wrapped in vinyon bottle Dress.

Comparative example 2

A kind of xylene monosulfonic acid Lapatinib tablet, including the composition of following weight proportion：

Preparation：This dosage form can be produced using conventional tablet pharmaceutical equipment, and concrete preparation method is as follows：Will Crude drug xylene monosulfonic acid Lapatinib is crossed 150 mesh sieves and is processed.Microcrystalline Cellulose and Mannitol cross 100 respectively Mesh sieve, then weighs according to quantity respectively with cross-linking sodium carboxymethyl cellulose, Hypromellose, and in order It is added sequentially to mix in crude drug, mix rotating speed 200rpm, cutter rotating velocity 400rpm；It is subsequently adding pure Change water and prepare soft material, speed of agitator is 400rpm, cutter rotating velocity is 800rpm.20 mesh sieves are pelletized after 50 DEG C Under the conditions of dry to moisture 2% about, after 24 mesh sieve granulate add recipe quantity sodium stearyl fumarate mix Even, carry out intermediates content detection, determine tabletting after piece weight, with OPADRY 17B620000 aqueous solution pair Gained label is coated, coating weight gain 2%, obtains tablet, specification 0.25g/ piece, final coated tablet in Vinyon bottle is packed.

Tablet (specification prepared by comparative example 1 and comparative example 2：0.25g/ piece) and former triturate (specification： 0.25g/ piece, Britain's GlaxoSmithKline PLC company, trade name) carry out Dissolution Rate Testing together. Dissolution Rate Testing method with reference to FDA dissolution data base recommend method, dissolving-out method used be paddle method, 55rpm, dissolution medium is respectively pH1.0 hydrochloric acid solution+0.5% tween of 900ml, pH6.8 phosphoric acid delays Rush liquid+2% tween.The dissolution medium of different pH is the physiological environment in order to simulate internal different parts, The dissolution characteristic of different medium relatively can reflect the quality conformance with former triturate to a certain extent. (see Fig. 5, Fig. 6)

Shown by above-mentioned result of the test, comparative example 1, the sample of comparative example 2 and former triturate are in pH1.0 Stripping curve under hydrochloric acid and pH6.8 phosphate buffer differs greatly, and final dissolution is significantly lower than former grinding Preparation.

Claims (10)

1. a kind of xylene monosulfonic acid Lapatinib tablet it is characterised in that：By containing following weight proportioning Crude drug xylene monosulfonic acid Lapatinib and adjuvant silica sol are prepared from：

45～60 parts of xylene monosulfonic acid Lapatinib, 0.25～2 part of silica sol.

2. tablet according to claim 1 it is characterised in that：Described crude drug and adjuvant colloid The weight proportion of silicon dioxide is：

45～60 parts of xylene monosulfonic acid Lapatinib, 0.5～1.5 part of silica sol.

3. tablet according to claim 1 and 2 it is characterised in that：Described adjuvant also includes sweet Reveal alcohol, Microcrystalline Cellulose, disintegrating agent, binding agent, lubricant, coating pre-mixing agent, its weight proportion is：

10～30 parts of Mannitol, 15～35 parts of Microcrystalline Cellulose, 1～8 part of disintegrating agent, binding agent 1.5～6 Part, 0.3～1.8 part of lubricant, 0.5～6 part of coating pre-mixing agent；

Described disintegrating agent is carboxymethylstach sodium, one or two mixing in cross-linking sodium carboxymethyl cellulose； Binding agent is Hypromellose, Povidone K 30, one or more mixing in Hydroxypropyl Cellulose； Described lubricant is one of sodium stearyl fumarate, magnesium stearate, stearic acid, Pulvis Talci or two kinds Above mixing.

4. tablet according to claim 3 it is characterised in that：Described tablet is by following weight The raw material of proportioning and adjuvant are prepared from：

45～54 parts of xylene monosulfonic acid Lapatinib, 0.5～1.5 part of silica sol, Mannitol 15～25 Part, 20～30 parts of Microcrystalline Cellulose, 2～6 parts of cross-linking sodium carboxymethyl cellulose, Hypromellose 2.5～3.5 Part, 0.8～1.5 part of magnesium stearate, 1～6 part of coating pre-mixing agent.

5. tablet according to claim 4 it is characterised in that：It is former by following weight proportioning Material medicine and adjuvant are prepared from：

45～54 parts of xylene monosulfonic acid Lapatinib, 0.8～1.2 part of silica sol, Mannitol 15～20 Part, 22～26 parts of Microcrystalline Cellulose, 2～4 parts of cross-linking sodium carboxymethyl cellulose, Hypromellose 2.5～3.5 Part, 0.8～1.5 part of magnesium stearate, 1～4 part of coating pre-mixing agent；Described coating pre-mixing agent is OPADRY 17B620000.

6. tablet according to claim 5 it is characterised in that：It is former by following weight proportioning Material medicine and adjuvant are prepared from：

49～50 parts of xylene monosulfonic acid Lapatinib, 0.9～1 part of silica sol, Mannitol 18～19 Part, 24～25 parts of Microcrystalline Cellulose, 2～3 parts of cross-linking sodium carboxymethyl cellulose, Hypromellose 3～3.5 Part, 0.8～1.2 part of magnesium stearate, 1～3 part of coating pre-mixing agent；Described coating pre-mixing agent is OPADRY 17B620000.

7. the tablet described in claim 3～6 any one it is characterised in that：In described Mannitol 50% particle diameter is less than 100 μm, and 90% particle diameter is less than 250 μm.

8. the tablet described in claim 3～6 any one it is characterised in that：Described microcrystalline cellulose In element, 50% particle diameter is less than 150 μm, and 90% particle diameter is less than 250 μm.

9. the tablet described in claim 3～6 any one it is characterised in that：Described Microcrystalline Cellulose Model Microcrystalline Cellulose pH101, it is highly preferred that described Microcrystalline Cellulose model is Microcrystalline Cellulose KG802.

10. a kind of method preparing the tablet described in claim 3～9 any one, it includes walking as follows Suddenly：

1) xylene monosulfonic acid Lapatinib and silica sol are crossed 40～80 eye mesh screens respectively to process, claim Take recipe quantity to mix, then cross 100～200 mesh sieves and process, and will the two mix homogeneously；

2) Microcrystalline Cellulose, Mannitol cross 60～100 mesh sieves respectively, then by Microcrystalline Cellulose, manna Alcohol, disintegrating agent and binding agent weigh respectively according to quantity and are added to step 1) in mixture in, then in height Mix homogeneously under shearing wet granulator, mixes rotating speed preferably 200～400rpm, and cutter rotating velocity is preferred 200～800rpm；

3), during carrying out soft material preparation, soft material processed with purified water to above-mentioned mixing powder, speed of agitator is 200～400rpm, cutter rotating velocity is 300～1200rpm；The sieve number pelletized is 16～30 mesh；

4) granule of preparation is dried, drying temperature is 50～60 DEG C, drying moisture to 1.0～3.5%, Dry granulate mesh number preferably 16～24 mesh of granule；

5) to step 4) in gained granule add lubricant, mixing, incorporation time be 5～10min；

6) coating, obtains tablet.