CN104248769B - A kind of lurasidone medicine composition and preparation method thereof - Google Patents

Abstract

The present invention provides a kind of lurasidone medicine composition, and containing Lurasidone or its acid-addition salts and cyclodextrin, wherein the molar ratio of Lurasidone or its acid-addition salts and cyclodextrin is 1:1 ~ 2.Lurasidone medicine composition provided by the invention is prepared into oral solid formulation, is not required to carry out raw material particle size harsh limitation, avoids wastage of material, be prepared into injection sterile powder, can make Lurasidone excellent dissolution, avoids that organic solvent is added.

Description

A kind of lurasidone medicine composition and preparation method thereof

Technical field

The present invention relates to a kind of preparation compositions and preparation method thereof of resisting mental disease drug, and in particular to a kind of Shandong drawing The preparation compositions and preparation method thereof of western ketone.

Background technique

Lurasidone HCl, chemical name: (3aR, 4S, 7R, 7aS) -2- { (1R, 2R) -2- [4- (1,2- benzisothia Azoles -3- base) piperazine -1- ylmethyl] cyclohexyl methyl } hexahydro -4,7- methylene -2H- iso-indoles -1,3- dione hydrochloride.

This product is a kind of atypical antipsychotic, and U.S. FDA in October, 2010 ratifies SUMITOMO CHEMICAL drugmaker The listing of Lurasidone HCl tablet, trade name Latuda, suitable for the treatment of schizophreniac, the effect of Lurasidone Mechanism is not yet clear.It has been suggested that validity of the Lurasidone in schizophrenia is by 2 type dopamine of maincenter (D2) and the joint antagonism of 2 type five hydroxytryptamine (5HT2A) receptors and mediate, it is equal to the positive and negative symptoms of mental patient With significant curative effect, in addition Lurasidone can also improve cognitive function.Recommendation initial dose is 40mg/d, effective dosage ranges For 40 ~ 120mg/d, maximum recommended dosage is 80mg/d；Lurasidone should be taken simultaneously with food.Lurasidone is less to cause body Increase again, glucose, lipid (lipoid), ECG and QT interphase is not caused to change.

In order to play so that quick-acting, onset time is short, the drug effect of desired Lurasidone characterized by duration, said preparation Expect that there is immediate release.The administration of oral preparation, especially solid pharmaceutical preparation are often thought of as most common and in many diseases Disease treatment in it is preferable to use.But since Lurasidone is insoluble drug, can not be obtained under many prescription formulation conditions Sufficient immediate release.It is mainly the following solution at present, one kind is formed into containing pre-gelatinized starch, water soluble excipient With the preparation of water-soluble copolymer adhesive, and 0.1-8 μm is limited to the average grain diameter of Lurasidone (CN200680018223.4 and division CN201010564784.2)；Second of preparation includes Lurasidone, cellulose derivative And sugar alcohol.The Lurasidone tablet of preparation not only has good release performance, but also has good mechanical performance (CN201210206844.2)；Or surfactant (CN 201210206877.7) is added on this basis, reduce Lurasidone The contact angle on pharmaceutical composition surface and water is more advantageous to drug release, and wherein the average grain diameter of Lurasidone is limited to 0.1-8μm；The third preparation contains the micronized particle, microcrystalline cellulose and water-soluble polymer of Lurasidone and dispersible carrier Adhesive after this method first mixes Lurasidone with dispersible carrier, disperses to form micro mist using grinding and the method crushed Change particle, is granulated after microcrystalline cellulose is then added using adhesive, wherein the micronized particle of Lurasidone and dispersible carrier Average grain diameter be 0.1-12 μm；4th kind of preparation is Lurasidone oral disintegrating tablet, and same Lurasidone and water-soluble filler are mixed Micronization processes after conjunction, partial size are 0.1-10 μm.

CN200680018223.4 and division CN201010564784.2: the present invention relates to a kind of oral administration preparations, should Preparation contains: pre-gelatinized starch, and Lurasidone HCl is as active constituent, water soluble excipient, water-soluble copolymer adhesive, The preparation has constant dissolution characteristic, even if being also such when the content of its active constituent changes.Lurasidone 10- 160mg content 20-45% weight, the combined amount of pre-gelatinized starch are 10-50%.Its division is further to the average grain of Lurasidone Diameter has carried out being limited to 0.1-8 μm；It is defined with the amount of water soluble excipient as 30-80%.

CN201210206844.2: the invention discloses Lurasidone tablets and preparation method.Lurasidone tablet, packet It includes: Lurasidone, cellulose derivative and sugar alcohol.The preparation of the Lurasidone of preparation especially tablet not only has good release Performance is put, but also there is good mechanical performance.

CN201210206877.7: the invention discloses the pharmaceutical composition of Lurasidone and preparation methods.The Lu Laxi Ketone pharmaceutical composition comprising: Lurasidone, sugar alcohol, disintegrating agent, adhesive and surfactant and optional water are insoluble Property filler.The contact angle of lurasidone medicine composition of the present invention, surface and water is not more than 95 degree.Lurasidone of the present invention Preparation especially tablet not only there is good release performance, but also there is good mechanical performance.The present invention is in CN 201210206844.2 surfactant is added on the basis of, reduces contact of the lurasidone medicine composition surface with water in this way Angle.

The administration of the above oral preparation, especially solid pharmaceutical preparation are often thought of as most common and in many diseases Treatment in it is preferable to use.But schizophreniac or patients with Alzheimer disease is each has extensive symptom by oneself, therefore, have When to treat such patient only by oral solid formulation not enough, for example, the schizophrenia for acute attack stage Patient refuses the patient of administration, the elderly of swallow difference, and the patient with dysphagia.In addition, this technology is adopted With wet granulation (or fluidized bed granulation) tabletting, art for coating, technique is cumbersome, higher cost.

CN201210519854.1: the invention discloses a kind of preparation and preparation method thereof containing Lurasidone HCl. Said preparation contains the micronized particle, microcrystalline cellulose and water-soluble copolymer adhesive of Lurasidone HCl and dispersible carrier, More particularly it relates to oral preparation, especially tablet, said preparation has faster dissolution characteristic, and having the same Active constituent dissolution characteristic, even if being also in this way, wherein Shandong is drawn when the content of its active constituent changes in a certain range The average grain diameter of the micronized particle of western ketone and dispersible carrier is 0.1-12 μm.

CN201210589694.8: the invention discloses Lurasidone hydrochloride orally-disintegratintablet tablets and preparation method thereof.This hair The bright oral disintegrating tablet each component and its mass percent are as follows: Lurasidone HCl 5%-60%, filler 25%-80%, disintegrating agent 5%- 20%, wetting agent 0.02%-0.15%, corrigent 0.2%-5%, lubricant 0.5%-2%, wherein Lurasidone and water-soluble filler Micronization processes after mixing, partial size are 0.1-10 μm.

As can be seen that above technical scheme has a common trait, i.e., preparation is made again after must being micronized raw material, with Accelerate the release of drug.Raw material micronization mainly uses physical crushing method in production at present, such as mechanical crushing method and air-flow crushing Method, these methods are by physical grinding comminuting matter, and process of lapping loss of material is big, and yield is low, and abrasive media is long with material Phase contact is it is also possible to pollute, and frictional heat generation destroys the pharmacological property of thermal sensitivity drug, and furthermore micronization process also increases energy consumption, Extend manufacturing cycle, reduces production efficiency.

In addition, being directed to the schizophrenic patients of acute attack stage, refuses the administration of the patient or gerontal patient of medication, also set The oral preparation or ejection preparation for having counted liquid form, mainly for the schizophrenic patients of acute attack stage, refusal medication Patient or gerontal patient administration, be such as added and at least one be selected from benzylalcohol, n,N-dimethylacetamide, lactic acid, dehydrated alcohol Make the solution type preparation (CN200680021027.2) of Lurasidone solubilising with the substance of propylene glycol；It include that Shandong is drawn there are also one kind The liquid preparation (CN201210205833.2) of western ketone, polyhydroxy alcohol and water.

CN200680021027.2: the present invention relates to a kind of solution type preparation, containing Lurasidone free form or its Pharmaceutically acceptable acid addition salts are as active constituent, wherein at least one selected from benzylalcohol, n,N-dimethylacetamide, cream by being added Acid, dehydrated alcohol and propylene glycol substance and keep active constituent solubilized.

CN201210205833.2: the invention discloses a kind of lurasidone medicine composition and preparation methods.Composition includes: Lurasidone, polyhydroxy alcohol and water.Preparation method includes being dissolved in Lurasidone in suitable polyhydroxy-alcohol, and water is added, adds Enter optional other additives, adds polyhydroxy-alcohol to prescription full dose, optionally gained liquid composition is sterilized or removed Bacterium, sealed package to get.Lurasidone medicine composition of the present invention is suitble to gerontal patient and the ill-matched patient that takes medicine.

If the free form of the Lurasidone of indissoluble or its acid-addition salts can be prepared to solution type preparation, it can be with In extensive formulation art application, including parenteral preparation (such as injection) or oral liquid, and can provide a variety of Method that is convenient and effectively treating more patients.But since Lurasidone or its free form in water solubility less than Several mcg/mls are difficult to prepare so far the aqueous solution type preparation containing high concentration Lurasidone or its free form, also not The method of solubilized Lurasidone and its free form in research water outlet.Both the above invention mainly using be added organic solvent into Row solubilising, potential problem is that organic solvent may damage patient, generates such as local stimulation, haemolysis, neurotoxicity Deng therefore, the type of organic solvent, dosage or content are restricted in solution.In addition there are great hidden in terms of production safety Suffer from, harm is also resulted in the health of the operator in production process, so should be avoided as far as possible in production process using.

To sum up, lack a kind of scheme in the prior art, it is difficult to provide a kind of increase on the basis of not limiting raw material particle size Soluble drug Lurasidone solubility, improves the lurasidone medicine composition of the dissolution rate of Lurasidone.

Summary of the invention

The present invention is based on the disadvantages mentioned above of the prior art, provide a kind of pharmaceutical composition containing Lurasidone inclusion compound And preparation method thereof, the present invention does not need raw material micronization, significant loss is small, the Lu Laxi of preparation without controlling raw material particle size One compositions, release is fast, quality and has good stability.

The object of the present invention is achieved like this: the present invention provides a kind of lurasidone medicine composition, it is characterised in that Containing Lurasidone or its acid-addition salts and cyclodextrin, wherein the molar ratio of Lurasidone or its acid-addition salts and cyclodextrin is 1: 1~2。

In a preferred embodiment, lurasidone medicine composition provided by the invention, it is characterised in that by Lurasidone Or its acid-addition salts, cyclodextrin, filler, disintegrating agent, adhesive and lubricant composition, wherein Lurasidone or its acid-addition salts Account for ratio 20 ~ 30% in composition, the ratio 50 ~ 70% of cyclodextrin, the ratio 10 ~ 25% of filler, the ratio 1 ~ 4% of disintegrating agent, The ratio 1 ~ 4% of adhesive, ratio < 1% of lubricant.

It is further preferred that Lurasidone or its acid-addition salts account in composition in above-mentioned lurasidone medicine composition Ratio 20%, the ratio 50% of cyclodextrin, the ratio 25% of filler, the ratio 1% of disintegrating agent, 1% in adhesive tablet, lubricant 0.5%。

One kind more preferably scheme is a kind of lurasidone medicine composition of the invention, it is characterised in that contain Shandong Western ketone or its acid-addition salts and cyclodextrin are drawn, wherein the molar ratio of Lurasidone or its acid-addition salts and cyclodextrin is 1:1 ~ 2, institute It states composition to be made of Lurasidone or its acid-addition salts, cyclodextrin, filler, disintegrating agent, adhesive and lubricant, wherein Shandong Western ketone or its acid-addition salts is drawn to account for ratio 20% in composition, the ratio 51.8% of cyclodextrin, the ratio 25.7% of filler, disintegration The ratio 1% of agent, 1% in adhesive tablet, lubricant 0.5%, wherein Lurasidone or its acid-addition salts are Lurasidone HCl, Cyclodextrin is hydroxypropyl-β-cyclodextrin, and filler is starch, and disintegrating agent is crospovidone, and adhesive is hydroxypropyl methylcellulose Element, lubricant are magnesium stearate.

The above lurasidone medicine composition is for being administered orally.

Above-mentioned lurasidone medicine composition can also be coated, and carry out film coating using Opadry II, coating increases Weight is about the 2% of label weight.

In another preferred embodiment, lurasidone medicine composition provided by the invention, it is characterised in that by Lu Laxi Ketone or its acid-addition salts, cyclodextrin and filler composition, wherein Lurasidone or its acid-addition salts account for ratio 20 in composition ~ 30%, cyclodextrin 30 ~ 60%, the ratio 25 ~ 45% of filler.

The lurasidone medicine composition is used for drug administration by injection.

In lurasidone medicine composition provided by the invention, the Lurasidone acid-addition salts select Lurasidone hydrochloric acid One of salt, sulfate, malate, oxalates or tartrate, preferably Lurasidone HCl.

The cyclodextrin selects alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, hydroxypropyl-β-cyclodextrin, sulfobutyl ether- Any one or more mixtures, preferably beta-cyclodextrin or hydroxypropyl-β-cyclodextrin in beta-cyclodextrin.

The filler select starch, sucrose, dextrin, mannitol, lactose, in microcrystalline cellulose it is any one or two kinds of with On mixture.It is preferred that mannitol or lactose.

The disintegrating agent is selected from crospovidone, sodium carboxymethyl starch, calcium carboxymethylcellulose, cross-linked carboxymethyl fiber One of plain sodium, low substituted hydroxy-propyl methylcellulose and dried starch are a variety of, preferably crospovidone, sodium carboxymethyl starch Or croscarmellose sodium.

Described adhesive selects any one of starch slurry, hydroxypropyl methylcellulose, povidone and syrup or two or more Mixture, preferably hydroxypropyl methylcellulose or povidone.

The lubricant is selected stearic acid, magnesium stearate, calcium stearate, superfine silica gel powder, talcum powder, hydrogenated vegetable oil, is gathered Any one of ethylene glycol 6000, Macrogol 4000, lauryl sodium sulfate, fumaric acid odium stearate are two or more mixed Close object, preferably magnesium stearate.

The above components percentage is weight percentage example.

Lurasidone medicine composition provided by the invention, there are two types of schemes for specific preparation method:

Preparation method one comprises the following steps:

1) Lurasidone cyclodextrin inclusion compound prepare: weigh cyclodextrin stirring and dissolving into water, weigh Lurasidone or its Ethanol solution is added in cyclodextrin aqueous solution acid-addition salts stirring and dissolving into ethyl alcohol, continues stirring to solution and clarifies, spraying It is drying to obtain Lurasidone cyclodextrin inclusion compound.

2) fluidized bed granulation: Lurasidone inclusion compound obtained by step 1) and filler, disintegrating agent are added in fluidized bed, mixed After closing uniformly, adhesive granulation is added.

3) it mixes: lubricant will be added in particle, be uniformly mixed.

4) tabletting: said mixture is tabletted.

Method one made above is obtained for for oral lurasidone medicine composition.

Preparation method two comprises the following steps:

1) preparation of Lurasidone cyclodextrin inclusion compound solution: cyclodextrin stirring and dissolving into water is weighed, Lu Laxi is weighed Ethanol solution is added in cyclodextrin aqueous solution ketone or its acid-addition salts stirring and dissolving into ethyl alcohol, and it is clear to solution to continue stirring Clearly, filler is added, stirring to all dissolutions is to get Lurasidone cyclodextrin inclusion compound solution.

2) it is freeze-dried: by step 1) acquired solution filtration sterilization, being filled into cillin bottle and be freeze-dried, seal, i.e., Obtain lurasidone medicine composition.

The method two made above lurasidone medicine composition obtained for for injection.

Lurasidone medicine composition provided by the invention is prepared into oral solid formulation, is not required to carry out raw material particle size severe Limitation is carved, wastage of material is avoided, and saves and the processing steps such as is ground up, sieved, production efficiency is improved, in addition, pharmaceutical composition of the present invention Object is prepared into injection sterile powder, can make Lurasidone excellent dissolution, avoids that organic solvent is added, reduces the poison to human body Evil.Experiment proves that stability is substantially better than commercialized product.

Specific embodiment

Following embodiment is illustrated to of the invention, should not be construed as limiting to the scope of the present invention.

Embodiment 1

Composition:

40 g of Lurasidone HCl

86 g of hydroxypropyl-β-cyclodextrin

Lactose 27.5g

3.5 g of croscarmellose sodium

2 g of hydroxypropyl methylcellulose

1 g of magnesium stearate

Preparation method: adding to stirring and dissolving in water for hydroxypropyl-β-cyclodextrin, Lurasidone HCl is added molten in ethyl alcohol Ethanol solution is added in aqueous solution solution, continues stirring to solution and clarifies, is spray-dried cyclodextrin encapsulated up to Lurasidone Object.Lurasidone inclusion compound and lactose, croscarmellose sodium are added in fluidized bed, after mixing, hydroxypropyl is added Methylcellulose granulation.Magnesium stearate is added, mixes, is pressed into 1000.

Embodiment 2

Composition:

40 g of Lurasidone HCl

114 g of hydroxypropyl-β-cyclodextrin

28.5 g of lactose

8 g of sodium carboxymethyl starch

8 g of hydroxypropyl methylcellulose

1 g of magnesium stearate

Preparation method: adding to stirring and dissolving in water for hydroxypropyl-β-cyclodextrin, Lurasidone HCl is added molten in ethyl alcohol Ethanol solution is added in aqueous solution solution, continues stirring to solution and clarifies, is spray-dried cyclodextrin encapsulated up to Lurasidone Object.Lurasidone inclusion compound and lactose, sodium carboxymethyl starch are added in fluidized bed, after mixing, hypromellose is added Element granulation.Magnesium stearate is added, mixes, is pressed into 1000.

Embodiment 3

Composition:

40 g of Lurasidone HCl

128 g of beta-cyclodextrin

22.5 g of mannitol

4 g of sodium carboxymethyl starch

4 g of povidone

1.5 g of magnesium stearate

Preparation method: adding to stirring and dissolving in water for beta-cyclodextrin, and Lurasidone HCl is added in ethyl alcohol and is dissolved, by second Alcoholic solution is added in aqueous solution, continues stirring to solution and clarifies, is spray-dried up to Lurasidone cyclodextrin inclusion compound.Shandong is drawn Western ketone inclusion compound and mannitol, sodium carboxymethyl starch are added in fluidized bed, after mixing, povidone granulation are added.It is added hard Fatty acid magnesium mixes, is pressed into 1000.

Embodiment 4

Composition:

40 g of Lurasidone HCl

103 g of hydroxypropyl-β-cyclodextrin

51 g of starch

2 g of crospovidone

2 g of hypromellose

1 g of magnesium stearate

Preparation method: adding to stirring and dissolving in water for hydroxypropyl-β-cyclodextrin, Lurasidone HCl is added molten in ethyl alcohol Ethanol solution is added in aqueous solution solution, continues stirring to solution and clarifies, is spray-dried cyclodextrin encapsulated up to Lurasidone Object.Lurasidone inclusion compound and starch, crospovidone are added in fluidized bed, after mixing, hydroxypropyl methylcellulose is added Element granulation.Magnesium stearate is added, mixes, is pressed into 1000.

Embodiment 5

Composition:

80 g of Lurasidone HCl

172 g of beta-cyclodextrin

40 g of mannitol

3 g of croscarmellose sodium

3 g of hypromellose

2 g of magnesium stearate

Preparation method: adding to stirring and dissolving in water for beta-cyclodextrin, and Lurasidone HCl is added in ethyl alcohol and is dissolved, by second Alcoholic solution is added in aqueous solution, continues stirring to solution and clarifies, is spray-dried up to Lurasidone cyclodextrin inclusion compound.Shandong is drawn Western ketone inclusion compound and mannitol, croscarmellose sodium are added in fluidized bed, after mixing, hydroxypropyl methylcellulose are added Element granulation.Magnesium stearate is added, mixes, is pressed into 1000.

Embodiment 6

Composition:

80 g of Lurasidone HCl

132 g of hydroxypropyl-β-cyclodextrin

88 g of mannitol

Preparation method: weighing cyclodextrin stirring and dissolving into water, and Lurasidone HCl is added in ethyl alcohol and is dissolved, by ethyl alcohol Solution is added in aqueous solution, continues stirring to solution and clarifies, and mannitol is added, stirring to all dissolutions is to get Lurasidone ring Cyclodextrin inclusion compound solution；It by acquired solution filtration sterilization, is filled into cillin bottle and is freeze-dried, seal to get Lurasidone Pharmaceutical composition.

Embodiment 7

Composition:

80 g of Lurasidone HCl

100 g of beta-cyclodextrin

120 g of lactose

Preparation method: weighing cyclodextrin stirring and dissolving into water, and Lurasidone HCl is added in ethyl alcohol and is dissolved, by ethyl alcohol Solution is added in aqueous solution, continues stirring to solution and clarifies, and lactose is added, stirring to all dissolutions is to get Lurasidone ring paste Inclusion compounds solution；It by acquired solution filtration sterilization, is filled into cillin bottle and is freeze-dried, seal to get Lurasidone medicine Compositions.

Comparative example 1(CN201210206877.7 embodiment 7)

Composition:

40 g of Lurasidone HCl

60 g of mannitol

45.5 g of cornstarch

3 g of sodium carboxymethyl starch

3.5 g of hypromellose

4 g of polysorbate65

4 g of magnesium stearate

Preparation method: 0.1 ~ 5 μm of Lurasidone HCl average grain diameter

(1) prepare the solution containing hypromellose and polysorbate65: water intaking is appropriate, and the hydroxypropyl of recipe quantity is added thereto Methylcellulose and polysorbate65, the concentration 5% of hypromellose, the concentration 5.71% of polysorbate65.

(2) it pelletizes: Lurasidone (being crushed to partial size 0.2-5um in advance), mannitol and starch (is crushed and cross 80 mesh Sieve), disintegrating agent (crush and sieve with 100 mesh sieve), be fitted into high-speed stirred pelletizer and be sufficiently stirred；Then step (1) is added Binder solution, carry out high-speed stirred granulation.Obtained particle is subjected to whole grain, drying；Add into resulting particle powder Enter lubricant, mix, obtain for tableting granulation.

(3) tabletting: the hardness of tablet is controlled in 5-6kgf(i.e. 49 ~ 59 N) in the range of, it is made 1000.

Comparative example 2

Identical as the composition of comparative example 1 and preparation method, difference is that raw material is not micronized, has carried out simple powder It is broken, 50 μm of average grain diameter.

Comparative example 3(CN201010564784.2 embodiment 2)

Composition:

40 g of Lurasidone HCl

72 g of mannitol

40 g of part pre-gelatinized starch

2 g of croscarmellose sodium

4 g of hypromellose

2 g of magnesium stearate

Preparation method: 0.1 ~ 8 μm of Lurasidone HCl average grain diameter.Using fluidized bed granulation, by Lurasidone and sweet dew The auxiliary materials such as alcohol after mixing, will be made into after pelletizing and dry in certain density binder solution penetrating fluidized bed, add Additional disintegrating agent and lubricant mix well, and are pressed into 1000.

Comparative example 4

Identical as the composition of comparative example 3 and preparation method, difference is that raw material is not micronized, has carried out simple It crushes, 50 μm of average grain diameter.

Comparative example 5(CN201210519854.1 embodiment 1)

Composition:

120 g of Lurasidone HCl

120 g of mannitol

195 g of microcrystalline cellulose

24 g of croscarmellose sodium

6.9 g of hydroxypropyl methylcellulose

9 g of silica

9 g of magnesium stearate

Preparation method:

1) that supplementary material is crossed 40 meshes is spare.

2) recipe quantity Lurasidone HCl and mannitol are weighed, is crushed after mixing, the micro mist of Lurasidone and dispersible carrier The average grain diameter for changing particle is 0.1-12 μm.

3) after microcrystalline cellulose, croscarmellose sodium mixing are added in above-mentioned particle, it is fine that 5% hydroxypropyl first is added Tie up plain solution softwood, the granulation of 14 mesh, 55 DEG C of dryings to weightless 1 ~ 3%, 14 mesh whole grains.

4) silica is added, magnesium stearate is uniformly mixed.

5) 1000 are pressed into.

Pass through the quality of following experiment investigation lurasidone medicine composition of the present invention.

8 dissolution rate of embodiment

Dissolution determination is carried out to embodiment 1-5 sample, comparative example 1-5 sample and commercialized product: shining dissolution method (two annex of Chinese Pharmacopoeia version in 2010, Ⅹ the second method of C), using pH3.8 Mcllvaine buffer solution 900ml as dissolution medium, Revolving speed is 50 turns per minute, is operated according to methods, and is sampled through 20 minutes, using high effective liquid chromatography for measuring.Chromatographic condition: octane is used Base silane bonded silica gel is filler, and with 0.01mol/L sodium heptanesulfonate (with phosphoric acid tune pH value to 3.0): acetonitrile (90:10) is Mobile phase A, using acetonitrile as Mobile phase B, using A:B=66:34 as mobile phase, flow velocity 1.2ml/min, Detection wavelength 230nm, Chromatogram column temperature is 40 DEG C.Dissolution results are shown in Table 1.

1 dissolution results of table

The above test result explanation, the present invention can reach and comparative example and commercially available product LATUDA without controlling raw material particle size Similar or better dissolution, release rapidly, have achieved the purpose that rapid-action.

9 study on the stability of embodiment

Lurasidone HCl medicine is investigated according to 2010 editions two annex " medicine stability test guideline " of Chinese Pharmacopoeia The stability of compositions.

A collection of sample is prepared according to the method for the embodiment of the present invention 1, carries out study on the stability, sample places condition and investigation Project is shown in Table 2.

Table 2 investigates project and condition

Sample stability experimental result is shown in Table 3.

3 stability experiment result of table

Conclusion: through study on the stability, indices change compared with 0 day without conspicuousness this product, illustrate involved in the present invention Lurasidone HCl pharmaceutical composition and preparation method stablize it is feasible.

Embodiment 10 redissolves test

Embodiment 6-7 products obtained therefrom is subjected to redissolution test, the results showed that, the products obtained therefrom of embodiment 6 and 7 can obtain clear Clear solution, Lurasidone can be effectively improved using cyclodextrin encapsulated resulting injection Lurasidone sterile lyophilized powder by, which illustrating, exists Solubility in water avoids that poisonous and hazardous organic solvent is added.

Claims (1)

1. a kind of Lurasidone tablet, which is characterized in that

Composition: Lurasidone HCl 40g, hydroxypropyl-β-cyclodextrin 86g, lactose 27.5g, croscarmellose sodium 3.5g, Hydroxypropyl methylcellulose 2g, magnesium stearate 1g；

Preparation method: adding to stirring and dissolving in water for hydroxypropyl-β-cyclodextrin, and Lurasidone HCl, which is added in ethyl alcohol, to be dissolved, will Ethanol solution is added in aqueous solution, continues stirring to solution and clarifies, is spray-dried up to Lurasidone cyclodextrin inclusion compound, by Shandong It draws western ketone inclusion compound and lactose, croscarmellose sodium to be added in fluidized bed, after mixing, hydroxypropyl methylcellulose is added Magnesium stearate is added in granulation, mixes, and is pressed into 1000, saves before dissolving in the Lurasidone HCl addition ethyl alcohol ground Sieve step.