CN106539768B - A kind of Lurasidone HCl oral disnitegration tablet and preparation method thereof - Google Patents
A kind of Lurasidone HCl oral disnitegration tablet and preparation method thereof Download PDFInfo
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- CN106539768B CN106539768B CN201510600600.6A CN201510600600A CN106539768B CN 106539768 B CN106539768 B CN 106539768B CN 201510600600 A CN201510600600 A CN 201510600600A CN 106539768 B CN106539768 B CN 106539768B
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Abstract
The present invention provides a kind of oral disnitegration tablet of Lurasidone HCl containing insoluble drug, it includes: 8~24% Lurasidone HCls, 8~48% carriers, 0.8~4% adhesive, 24~76.2% fillers, 4~10% disintegrating agents, 2~6% corrigents, 1~4% lubricant, oral disnitegration tablet disintegration is rapid, for patient especially old man, children, comatose patient and inconvenient patient's medication of fetching water provide convenience, and dissolution in 5 minutes can reach 85% or more, its disintegration absorption rapidly in the oral cavity in addition, substantially increase its bioavilability, and it is easy to operate in production technology, production cost is low, it is suitable for industrialized large-scaled production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, it is related to a kind of Lurasidone HCl oral disnitegration tablet and preparation method thereof.
Background technique
Schizophrenia (schizophrenia) is a kind of psychiatric condition, is a kind of lasting, usually chronic great essence
Refreshing disease is one kind of most serious in mental disease, be with basic individual character, thinking, emotion, behavior division, cerebration and ring
The uncoordinated most common mental disease of one kind for main feature in border, more between twenty and fifty morbidities, and then influence behavior and emotion.Spirit
The primary symptom of Split disease is considered as that basic thinking structure and cognition are chipping.This dissociation phenomenon will cause thinking shape
Formula obstacle simultaneously leads to not differentiate inherent and external experience.The people of suffering from schizophrenia oneself may indicate illusion,
Alternatively, other people can be found that their performance is influenced by illusion.Patient may also express obvious vain hope conviction.
Lurasidone HCl (lurasidone hydrochloride, trade name) it is by SUMITOMO CHEMICAL system
The antipsychotic agent with double action of drug column type commercial firm exploitation, it is to 5-HT2AReceptor and dopamine D2Receptor is equal
With high affinity, significant curative effect is all had to the positive and negative symptoms of mental patient.It was on October 28th, 2010
Through Food and Drug Adminstration of the US (FDA) approval in U.S.'s listing for treating adult schizophrenia, Chinese chemical name:
(3aR, 4S, 7R, 7aS) -2- { (1R, 2R) -2- [4- (1,2- benzisothiazole -3- base) piperazine -1- ylmethyl] cyclohexyl first
Base } hexahydro -1H-4,7- methyl iso-indoles -1,3- dione hydrochloride；Molecular formula: C28H36N4O2S.HCl, molecular weight: 529.14,
Its structural formula are as follows:
Compared with other antipsychotic drugs, Lurasidone HCl has the advantage that 1, it is to dopamine D2Receptor, 5-
Hydroxytryptamine (5-HT7、5-HT2A、5-HT1A) and adrenaline α 2c receptor all have high affinity, to the positive of mental patient
Significant curative effect is all had with negative symptoms；2, Lurasidone is in addition to having height parent to the above-mentioned receptor that can improve memory defects
Outside power, acetylcholinergic receptor, histamine H are nor affected on1Receptor both be believed to destroy learning and memory function
Receptor, therefore also make moderate progress for the cognitive disorder of schizophreniac, in clinical research, by with other antipsychotics
The comparative study of drug, the mental patient that discovery Lurasidone has cognition dysfunction for treatment have extraordinary curative effect；
3, the adverse reaction (extrapyramidal symptom) of Lurasidone HCl is weaker, is not easy to cause the adverse reactions such as weight gain, hyperlipemia [envelope
Space flies, the pharmacology and clinical progress of antipsychotic new drug Lurasidone, Chinese Journal of New Drugs the 10th phase of volume 20 in 2011,
853-856 pages], therefore Lurasidone HCl is most one of the product of advantage in current antipsychotics, before the application of market
Scape is wide.
In the Lurasidone HCl listed at present, there is the ordinary tablet of five kinds of specifications of 20mg, 40mg, 60mg, 80mg, 120mg
Agent, drug release is slower, and disintegration rate is slow, is not suitable for having the patient of dysphagia or special circumstances to take, and for essence
Mind division patient is then more distinct issues because its mostly with dysphagia or " vacation is taken medicine " the characteristics of.Oral disnitegration tablet
Then have many advantages, such as that disintegration rate is fast, drug effect performance is fast, bioavilability is high, patient's compliance can be effectively improved, solve essence
Refreshing patient " vacation medication " problem, thus develop a kind of disintegration rapidly, dissolution rate height, simple production process, be suitble to it is industrial
Lurasidone HCl oral disnitegration tablet has very great meaning for expanding its clinical application range.
However, Lurasidone HCl is a kind of insoluble drug, and it is slightly molten in methyl alcohol, it is slightly soluble in ethyl alcohol, in acetone
Soluble,very slightly, this dissolution properties cause the dissolution of its preparation and disintegration to be restricted, the SUMITOMO CHEMICAL pharmacy strain of Yuan Yan company
Formula commercial firm discloses a kind of oral preparation using Lurasidone HCl as active constituent, but its in patent (CN101184489B)
Dosage form still falls within conventional tablet, does not have the characteristic of intraorally rapidly disintegrating, and its 10min dissolution rate is about 70-80%,
15min dissolution rate is about 80-90%, however can be seen that 5min dissolution rate is only 50% or so from its dissolution curve,
It is unable to reach the effect of Fast Stripping.A kind of Lurasidone HCl Orally disintegrating is disclosed in Chinese patent (CN103054824A)
Tablet preparation and preparation method thereof, using wet granule compression tablet after bulk pharmaceutical chemicals and hydrophilicity condiment are pulverized, to reach
To the purpose of Fast Stripping, this method operating process is complicated, and technique more falls behind, and preparation cost is high, and 15min dissolution can make molten
Out-degree reaches 90% or so, is unable to get rapid dissolution, and dissolution can be remarkably decreased under conditions of high humidity.
Summary of the invention
Fast Stripping and disintegration problem in view of insoluble drug, the present invention provide that a kind of disintegration rate is fast, dissolution rate
High, Lurasidone HCl oral disnitegration tablet that compressibility is strong, tablet stability is good and preparation method thereof.
Lurasidone HCl oral disnitegration tablet disclosed in this invention, by following weight percent at being grouped as: 8~
24% Lurasidone HCl, 8~48% carriers, 0.8~4% adhesive, 24~76.2% fillers, 4~10% disintegrating agents, 2
~6% corrigent, 1~4% lubricant.
Lurasidone HCl oral disnitegration tablet provided by the present invention, preferably by following weight percent at grouping
At: 12~20% Lurasidone HCls, 12~36% carriers, 1.6~3% adhesives, 38~60% fillers, 6~9% disintegrations
Agent, 2.5~5% corrigents, 1~3% lubricant.
Lurasidone HCl oral disnitegration tablet provided by the present invention, wherein Lurasidone HCl weight percent be preferably
16%.
Lurasidone HCl oral disnitegration tablet provided by the present invention, preferably by following weight percent at grouping
At: 16% Lurasidone HCl, 24% carrier, 2.4% adhesive, 45.6% filler, 7.5% disintegrating agent, 2.5% flavoring
Agent, 2% lubricant.
In above-mentioned Lurasidone HCl oral disnitegration tablet, the carrier be selected from lactose, mannitol, starch milk saccharide complex,
One of mannitol composites of starch is a variety of, preferably lactose and mannitol, further preferably mannitol.
In above-mentioned Lurasidone HCl oral disnitegration tablet, described adhesive is hydroxypropyl cellulose, hydroxypropyl methylcellulose, gathers
Vinylpyrrolidone it is one or more, preferably hydroxypropyl methylcellulose, polyvinylpyrrolidone it is one or more, further
Preferably hydroxypropyl methylcellulose.
In above-mentioned Lurasidone HCl oral disnitegration tablet, it is compound that the filler is selected from lactose, mannitol, starch lactose
The combination of object, mannitol composites of starch, microcrystalline cellulose, preferably mannitol, starch milk saccharide complex one or two
The combination of the combination of microcrystalline cellulose, further preferably mannitol and microcrystalline cellulose.
In above-mentioned Lurasidone HCl oral disnitegration tablet, the disintegrating agent is selected from carboxyrnethyl starch sodium, Croscarmellose
One of sodium, crospovidone are a variety of, preferably the one or two of crospovidone and croscarmellose sodium.
In above-mentioned Lurasidone HCl oral disnitegration tablet, the corrigent be selected from aspartame, Sucralose, acesulfame potassium,
One of lemon extract, Mint Essence, strawberry essence are a variety of.
In above-mentioned Lurasidone HCl oral disnitegration tablet, the lubricant is in silica, magnesium stearate, talcum powder
It is one or more.
In above-mentioned Lurasidone HCl oral disnitegration tablet, the Lurasidone average grain diameter is 0.1~10 μm, preferably
0.1~5 μm.
In above-mentioned Lurasidone HCl oral disnitegration tablet, the D of the diameter of carrier50It is 30 μm~200 μm, preferably 75~
160 μm, further preferably 160 μm.
Lurasidone oral disnitegration tablet provided by the invention, prescription is preferably by following weight percent at grouping
At: Lurasidone HCl 16%, carrier mannitol 12~36%, hydroxypropyl methylcellulose 1.6~3%, mannitol and microcrystalline cellulose
Element 38~60%, crospovidone 6~9%, corrigent 2.5~5%, lubricant 1~3%；The wherein Lurasidone HCl
Average grain diameter be 0.1~10 μm, the D of mannitol50It is 75~160 μm.
Lurasidone oral disnitegration tablet provided by the invention, prescription be further preferably by following weight percent at
It is grouped as: Lurasidone HCl 16%, carrier mannitol 24%, hydroxypropyl methylcellulose 2.4%, filler mannitol 20.6%,
Microcrystalline cellulose 25%, crospovidone 7.5%, Sucralose 2%, Mint Essence 0.5%, magnesium stearate 1%, silica
1%；Wherein the average grain diameter of the Lurasidone HCl is 0.1~5 μm, the D of mannitol50It is 160 μm.
Above-mentioned Lurasidone HCl oral disnitegration tablet, preparation method are as follows: it is molten that Lurasidone HCl is suspended in adhesive
Drug containing suspension is made in liquid, then is wrapped on carrier to be formed by spraying by drug containing suspension by fluidized bed and carries medicine particle, then
Be added remaining auxiliary material be uniformly mixed, tabletting to obtain the final product.
In above-mentioned Lurasidone HCl oral disnitegration tablet, described adhesive solution is that adhesive is dissolved in solvent to make
?.
In above-mentioned Lurasidone HCl oral disnitegration tablet, the solvent is the mixed solvent of ethyl alcohol and water composition.
In above-mentioned Lurasidone HCl oral disnitegration tablet, the ethyl alcohol and water composition mixed solvent concentration be 10%~
45%, preferably 40%.
In above-mentioned Lurasidone HCl oral disnitegration tablet, the weight ratio of described adhesive solution and Lurasidone HCl is 3:
1~8:1, preferably 5:1.
Preferred Lurasidone HCl oral disnitegration tablet provided by the invention, preparation methods steps are as follows:
(1) it takes recipe quantity hydroxypropyl methylcellulose to be dissolved in the mixed solution of suitable second alcohol and water, weighs the salt of recipe quantity
Sour Lurasidone is added in above-mentioned solution, and drug containing suspension is made in mechanical stirring, by the drug containing suspension by fluidized bed to carry
Body is spraying for bottom material, wraps up, dry, is made and carries medicine particle；
(2) it takes load medicine particle, recipe quantity filler obtained by step (1) to cross 50 meshes, takes recipe quantity disintegrating agent, flavoring
65 meshes are crossed in agent, lubricant, by after sieving remove lubricant all auxiliary materials be uniformly mixed, then plus mix lubricant it is uniform, tabletting
To obtain the final product.
Lurasidone HCl oral disnitegration tablet provided by the invention compared with prior art, has following advantage:
1, Lurasidone HCl oral disnitegration tablet of the invention disintegration is that patient especially old man, children, stupor are suffered from rapidly
Person and inconvenient patient's medication of fetching water provide convenience.
2, Lurasidone HCl oral disnitegration tablet of the invention significantly improves the dissolution rate of drug, and oral cavity is made and collapses
Solution dissolution in piece 5 minutes can reach 85% or more, it is disintegrated rapidly absorbs in the oral cavity in addition, substantially increase its biology benefit
Expenditure.
3, Lurasidone HCl Orally disintegrating tablet recipe of the invention is simple, and simple in production process operation, production cost
It is low, it is more suitable for industrialized production.
Below by specific embodiment, the present invention is described further:
In embodiment of the present invention and specific embodiment, dissolution rate involved in Lurasidone HCl oral disnitegration tablet is surveyed
It is specific as follows to determine method:
It is measured according to high performance liquid chromatography (two V D of annex of Chinese Pharmacopoeia version in 2010).
Chromatographic condition and system suitability are using octadecylsilane chemically bonded silica as packed column, with acetonitrile-
0.005mol/L dipotassium hydrogen phosphate solution (takes dipotassium hydrogen phosphate 0.87g, adds water to 1000ml, triethylamine 5ml is added, uses phosphoric acid
Adjust pH to 3.0) (50:50) be mobile phase, Detection wavelength 230nm, 30 DEG C of column temperature, flow velocity 1.0ml/min.Theoretical cam curve
2000 should be not less than by calculating by Lurasidone HCl.
This product is taken, according to dissolution method (two annex of Chinese Pharmacopoeia version in 2010, Ⅹ the second method of C), with McIlvaine
Buffer 3.8900ml is dissolution medium, and revolving speed is 50 turns per minute, operates according to methods, when through 5 minutes, 10 minutes, 15 minutes, takes
Dissolution fluid 6ml, filtration, takes subsequent filtrate as test solution, while the temperature such as supplement, isometric Jie into stripping rotor immediately
Matter.Lurasidone HCl reference substance about 22mg separately is taken, it is accurately weighed, it sets in 250ml measuring bottle, 5ml methanol is added to make to dissolve, then with molten
Medium dissolves and is diluted to scale out, shakes up, and precision measures 5ml, sets in 10ml measuring bottle, is diluted to scale with dissolution medium, shakes
It is even, as reference substance solution, above-mentioned test solution and contrast solution are taken, precision 20 μ l of amount injection liquid chromatograph simultaneously records chromatography
Figure, by external standard method with calculated by peak area to get.
In embodiment of the present invention and specific embodiment, to disintegration time limited involved in Lurasidone HCl oral disnitegration tablet
Measuring method is referring to (two revision annex XA of " Chinese Pharmacopoeia " version third enlarged edition in 2010).
It is uniform to content involved in Lurasidone HCl oral disnitegration tablet in embodiment of the present invention and specific embodiment
It is specific as follows to spend measuring method:
It is measured according to high performance liquid chromatography (two V D of annex of Chinese Pharmacopoeia version in 2010).
Chromatographic condition and system suitability are filler with octadecylsilane chemically bonded silica；With acetonitrile-
0.005mol/L dipotassium hydrogen phosphate solution (with phosphorus acid for adjusting pH to 7.0) (85:15) is mobile phase；Detection wavelength is 230nm；Reason
It is calculated by plate number by Lurasidone HCl peak and is not less than 2000.
Measuring method takes this product 1, sets in 100ml measuring bottle, adds diluent (60% acetonitrile-aqueous solution) in right amount, 20 points of ultrasound
Clock dissolves main ingredient, places room temperature, then be diluted to scale with diluent, shakes up, and filters, and precision measurement subsequent filtrate is appropriate, adds dilute
Releasing agent and concentration is quantitatively made is that hydrochloric Lurasidone is the solution of 40 μ g as test solution in every 1ml.Separately take hydrochloric acid Shandong
Draw western ketone reference substance about appropriate, it is accurately weighed, add diluent (60% acetonitrile-aqueous solution) that hydrochloric Lu Laxi in every 1ml is made
Ketone is the solution of 40 μ g as reference substance solution.Precision measures above-mentioned 20 μ l of solution injection liquid chromatograph and records chromatogram,
By external standard method with calculated by peak area to get.
In embodiment of the present invention and specific embodiment, the Lurasidone HCl oral disnitegration tablet the preparation method comprises the following steps:
Taking adhesive is dissolved in the mixed solution of second alcohol and water, then Lurasidone macro powder is added in the solution, mechanical stirring, system
At drug containing suspension, which is sprayed carrier, carries medicine, it is dry, it is made and carries medicine particle；By obtained load medicine
Grain, filler cross 50 meshes, and disintegrating agent, corrigent, lubricant cross 65 meshes, and all auxiliary materials that lubricant is removed after sieving are mixed
Uniformly, then plus mix lubricant it is uniform, tabletting to obtain the final product.
In embodiment of the present invention and specific embodiment, used material, drug, reagent, instrument are as follows:
Table 1 tests material
| Test material | Source | Lot number |
| Lurasidone HCl | Beijing Sun-Novo Pharmaceutical Research Co., Ltd. | 150324 |
| Mannitol | French Roquette Freres | 150101 |
| Lactose | French Roquette Freres | 100245410 |
| Starch | Anhui Shanhe Medicinal Subsidiary Material Co., Ltd. | 150203 |
| Microcrystalline cellulose | Japanese Asahi Kasei Corporation | 141201 |
| Lactose starch compound | French Roquette Freres | YM044 |
| Mannitol composites of starch | French Roquette Freres | 150203 |
| Methylcellulose | Shanghai Colorcon Coating Technology Co., Ltd | SH354288 |
| Hydroxypropyl cellulose | Look forward to pharmaceutcal corporation, Ltd in Hunan | 150102 |
| Hydroxypropyl methylcellulose | Shanghai Colorcon Coating Technology Co., Ltd | PD384202 |
| Sodium carboxymethylcellulose | Look forward to pharmaceutcal corporation, Ltd in Hunan | 141115 |
| Polyvinylpyrrolidone | German BASF group | 140608 |
| Ethyl cellulose | Shanghai Colorcon Coating Technology Co., Ltd | F20141110 |
| Carboxyrnethyl starch sodium | French Roquette Freres | 141204 |
| Low-substituted hydroxypropyl cellulose | Anhui Shanhe Medicinal Subsidiary Material Co., Ltd. | 130405 |
| Crospovidone | Japanese Asahi Kasei Corporation | 140506 |
| Croscarmellose sodium | FMC Corp., the U.S. | FN125487 |
| Aspartame | Hunan Jiudian Pharmaceutical Co., Ltd | 201410010 |
| Sucralose | Liyang Wei Xin Biotechnology Co., Ltd | 1401015SS |
| Lemon extract | Gloomy scientific and technological (China) Co., Ltd of fragrant essence pigment | 140101 |
| Mint Essence | Gloomy scientific and technological (China) Co., Ltd of fragrant essence pigment | 150102 |
| Strawberry essence | Gloomy scientific and technological (China) Co., Ltd of fragrant essence pigment | 141103 |
| Talcum powder | The medicinal talcum Co., Ltd of space flight | 150202 |
| Superfine silica gel powder | Look forward to pharmaceutcal corporation, Ltd in Hunan | 140302 |
| Magnesium stearate | Anhui Shanhe Medicinal Subsidiary Material Co., Ltd. | 150101 |
| Ethyl alcohol | Sichuan Kingsoft pharmaceutical Co. Ltd | 14100326 |
2 reference substance of table
| Reference substance title | Source | Lot number |
| Lurasidone HCl | PCL | 20150121C |
3 reagent of table
| Reagent name | Source | Lot number |
| Dipotassium hydrogen phosphate | Chengdu Ke Long chemical reagent factory | 20140203 |
| Citric acid | Hu'nan Erkang Pharmaceutical Co., Ltd. | 100820121201 |
| Disodium hydrogen phosphate | Chengdu Ke Long chemical reagent factory | 20150101 |
| Acetonitrile | Honeywell | 100269 |
| Methanol | Honeywell | 100296 |
| Triethylamine | Chongqing Chuan Dong chemical industry (group) Co., Ltd | 20130401 |
| Phosphoric acid | Chengdu Ke Long chemical reagent factory | 2013111501 |
| Purified water | Self-control | — |
4 instrument of table
| Instrument title | Producer | Model |
| High performance liquid chromatograph | Shimadzu (China) Co., Ltd | LC-2010CHT |
| Oral disintegrating tablet disintegration tester | Tianjin Tianda Tianfa Science and Technology Co. Ltd. | KB-1 |
| Digestion instrument | Tianjin Tianda Tianfa Science and Technology Co. Ltd. | RCZ-8M |
| Tablet press machine | Beijing Gylongli Sci.&Tech. Co., Ltd. | DP30A |
| Three-dimensional mixer | Precious mechanical (Shenzhen) Co., Ltd in Wall | T2F |
| Tablet hardness meter | Shanghai Huanghai Sea medicine inspection Instrument Ltd. | YPD-200C |
| Fluidized bed | Yingge Granulating Covering Technology Co., Ltd., Chongqing | WBF-3G |
| Airslide disintegrating mill | Shanghai Sai Shan powder machinery Co., Ltd | YQ50 |
| Laser particle size analyzer | Jinan Winner Particle Technology Co., Ltd. | Winner2308 |
| Powder general performance test | German PHARMA-TEST company | PTG S4 |
Judgment criteria:
In terms of disintegration time limited, its inspection is specified in two revision annex XA of " Chinese Pharmacopoeia " version third enlarged edition in 2010
Survey method and judgment criteria should be disintegrated completely in 60 seconds.
Uniformity of dosage units evaluation index: A+1.8S value should be less than 15.
Comparative example 1
According to different prescriptions, the Lurasidone HCl oral disnitegration tablet (slice weight 250mg) of different prescriptions is prepared, specifically
Prescription is shown in Table 5.Preparation method are as follows: take partial size to be that 0.1~5 μm of Lurasidone HCl crosses 65 meshes spare, take mannitol, cream
It is spare that sugar, microcrystalline cellulose cross 50 meshes, take croscarmellose sodium, crospovidone, aspartame, Mint Essence,
Magnesium stearate, silica cross that 65 meshes are spare, all auxiliary materials in addition to lubricant are uniformly mixed, then plus mix lubricant
Uniformly, tabletting to obtain the final product.
5 Lurasidone HCl Orally disintegrating tablet recipe of table
Comparative example 2
Lurasidone HCl oral disnitegration tablet (slice weight 250mg) is prepared according to different prescriptions, prescription is shown in Table 6, preparation
Method: taking partial size to be that 0.1~5 μm of Lurasidone HCl crosses 65 meshes spare, and filler is taken to cross 50 sieves, disintegrating agent, corrigent,
It is spare that lubricant crosses 65 meshes；Lurasidone HCl macro powder, filler and disintegrating agent are mixed in wet granulator by prescription
It closes uniform.Binder solution is added into mixture, pelletizes；After taking out drying, corrigent is added and is lubricated in addition to magnesium stearate
Agent is uniformly mixed, then stiffened fatty acid magnesium is uniformly mixed, and tabletting to obtain the final product.
6 Lurasidone HCl Orally disintegrating tablet recipe of table
7 Lurasidone HCl oral disnitegration tablet testing result of table
Comparative example 3
According to different prescriptions, Lurasidone HCl oral disnitegration tablet (slice weight 250mg) is prepared, specific prescription is shown in Table 8,
The preparation method comprises the following steps: taking adhesive, is dissolved in the mixed solution of second alcohol and water, then Lurasidone HCl Lurasidone macro powder is set
In the solution, drug containing suspension is made in mechanical stirring.The suspension is sprayed carrier, carries medicine, it is dry, it is made and carries
Medicine particle；Obtained load medicine particle, filler are crossed into 50 meshes, takes disintegrating agent, corrigent, lubricant to cross 65 mesh, will be sieved
Afterwards except all auxiliary materials of magnesium stearate are uniformly mixed, then stiffened fatty acid magnesium is uniformly mixed, and tabletting to obtain the final product.
The different Lurasidone HCl Orally disintegrating tablet recipes of table 8
The different Lurasidone HCl oral disnitegration tablet testing results of table 9
Comparative example 4
Lurasidone HCl oral disnitegration tablet (slice weight 250mg) is prepared according to different prescriptions, prescription is shown in Table 10, specific to make
Preparation Method are as follows: taking adhesive is dissolved in the mixed solution of second alcohol and water, then Lurasidone macro powder is added in the solution, machine
Tool stirring, is made drug containing suspension, which is sprayed lactose carrier, carries medicine, dry, is made and carries medicine particle；It will
Obtained load medicine particle, filler cross 50 meshes, and disintegrating agent, corrigent, lubricant cross 65 meshes, and lubricant will be removed after sieving
All auxiliary materials be uniformly mixed, then plus mix lubricant it is uniform, tabletting to obtain the final product.
The different Lurasidone HCl Orally disintegrating tablet recipes of table 10
Dissolution rate and disintegration time limited detection are carried out to above-mentioned prescription, testing result is shown in Table 11.
The different Lurasidone HCl Orally disintegrating tablet dissolutions of table 11 and disintegration time limited testing result
(1) Lurasidone HCl partial size screens
It adjusts airslide disintegrating mill and crushes pressure, Lurasidone HCl bulk pharmaceutical chemicals are crushed to different-grain diameter range, by following
Prescription prepares Lurasidone HCl oral disnitegration tablet (slice weight 250mg), and detects to its dissolution rate, the different prescription groups in part
At being shown in Table 12, dissolution rate testing result is shown in Table 13.
The different Lurasidone HCl Orally disintegrating tablet recipes of table 12
| Supplementary material title | Prescription 1 (g) | Prescription 2 (g) | Prescription 3 (g) | Prescription 4 (g) |
| Lurasidone HCl (0.1~5 μm) | 40 | — | — | — |
| Lurasidone HCl (5~10 μm) | 40 | — | — | |
| Lurasidone HCl (10~15 μm) | — | — | 40 | — |
| Lurasidone HCl (15~20 μm) | — | — | — | 40 |
| Lactose (carrier) (D50It is 120 μm) | 80 | 80 | 80 | 80 |
| Hydroxypropyl methylcellulose | 8 | 8 | 8 | 8 |
| Mannitol composites of starch | 55.5 | 55.5 | 55.5 | 55.5 |
| Microcrystalline cellulose | 40 | 40 | 40 | 40 |
| Croscarmellose sodium | 10 | 10 | 10 | 10 |
| Aspartame | 6 | 6 | 6 | 6 |
| Mint Essence | 1.5 | 1.5 | 1.5 | 1.5 |
| Magnesium stearate | 3 | 3 | 3 | 3 |
| Silica | 6 | 6 | 6 | 6 |
| It is total | 250 | 250 | 250 | 250 |
The Lurasidone HCl Orally disintegrating tablet dissolution testing result of the different prescriptions of table 13
With the increase of partial size it can be seen from the above results, the dissolution of Lurasidone HCl oral disnitegration tablet significantly becomes
Slowly, when Lurasidone HCl partial size is in 0.1~10 μ m, dissolution rate is higher, therefore, controls its partial size in 0.1~10 μ
Within the scope of m, preferably 0.1~5 μm.
(2) diameter of carrier screens
Select different average grain diameter (D50) lactose as carrier, be former with the Lurasidone HCl that partial size is 0.1~5 μm
Material, prepares Lurasidone HCl oral disnitegration tablet (slice weight 250mg) by following prescription, to load medicine particle yield, hydrochloric acid obtained
The uniform situation of Lurasidone oral disnitegration tablet content and dissolution rate and disintegration time limited are detected, and the optimal of carrier is filtered out
Particle size range, the different compositions in part are shown in Table 14, and testing result is shown in Table 15.
14 Lurasidone HCl Orally disintegrating tablet recipe of table
The different prescription Lurasidone HCl oral disnitegration tablet testing results of table 15
It can be seen that from upper result as carrier average grain diameter D50When being 30~240 μm, self-control Lurasidone HCl oral cavity collapses
Solving piece, it is dissolved out fastly, and disintegration meets regulation.Diameter of carrier D in prescription 550When being 30 μm, the loss of fluidized bed drug incorporation is big, yield
It is low.As carrier average grain diameter D50When being 240 μm, although carrying, medicine particle yield is higher, and uniformity of dosage units is against regulation, when
Carrier average grain diameter D50When being 75 μm~200 μm, yield is higher, the tablet content uniformity meets regulation.Therefore, control vector is flat
Equal partial size D50It is 30 μm~200 μm, preferably 75 μm~160 μm, further preferably 160 μm.
Present invention applicant is found through experiments that, when Lurasidone HCl is lower than 20mg, can also be obtained using this method compared with
The oral disnitegration tablet of good dissolution and disintegration effect, but comprehensive preparation carries medicine demand and considers, select Lurasidone HCl content for
20mg~60mg, preferably 30mg~50mg, further preferably 40mg.
Present invention applicant is further found through experiments that, when carrier is starch or microcrystalline cellulose, obtained mouth
The dissolution rate of cavity disintegrating tablet or disintegration time limited significantly reduce, when carrier is lactose, mannitol, starch milk saccharide complex, mannitol
When composites of starch, obtained Orally disintegrating tablet dissolution and disintegration time limited are more excellent, optimal when wherein carrier is mannitol；
When adhesive be methylcellulose, sodium carboxymethylcellulose, ethyl cellulose when, the dissolution rate of obtained oral disnitegration tablet or
Disintegration time limited significantly reduces, obtained when adhesive is polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose
Orally disintegrating tablet dissolution or disintegration time limited it is more excellent, wherein adhesive be hydroxypropyl methylcellulose when it is optimal；When used
When filler is starch, the dissolution rate of obtained oral disnitegration tablet or disintegration time limited are significantly reduced, when filler is lactose, sweet
Reveal alcohol, starch milk saccharide complex, mannitol composites of starch, microcrystalline cellulose when, obtained Orally disintegrating tablet dissolution or
Disintegration time limited is more excellent, and when filler is the combination of mannitol or starch lactose and microcrystalline cellulose, oral disintegrating tablet obtained is molten
Out-degree or disintegration time limited are more excellent, and the ratio of mannitol or starch lactose and microcrystalline cellulose is 1:3~1:0.5 at this time, wherein filling out
Fill optimal when the combination that agent is mannitol and microcrystalline cellulose, the ratio of mannitol and microcrystalline cellulose is 1:1.21 at this time；When
When disintegrating agent is low-substituted hydroxypropyl cellulose, the dissolution rate of obtained oral disnitegration tablet or disintegration time limited are significantly reduced, when collapsing
When solution agent is croscarmellose sodium, crospovidone, carboxyrnethyl starch sodium, obtained Orally disintegrating tablet dissolution and collapse
The solution time limit is more excellent, optimal when wherein disintegrating agent is crospovidone.
Applicant also selects the solvent for preparing binder solution in technical process, is found by many experiments
When the mixed solution for using ethyl alcohol and water to form is as solvent, Lurasidone HCl disperses more fast in binder solution
Speed, forms that drug containing suspension is more uniform, and when using 10%~45% ethyl alcohol as solvent, Lurasidone HCl is being bonded
Dispersion effect is more preferable in agent solution, is suspended more uniformly, when using 40% ethanol solution as solvent, Lurasidone HCl
Dispersion effect is best in binder solution；When Lurasidone HCl and binder solution mass ratio are 1:3~1:8, drug containing
Suspension stability is good, without sedimentation phenomenon in technical process, but considers production efficiency and stabilization and reliability in continuous production,
It is preferred that Lurasidone HCl and binder solution mass ratio are 1:5.
Applicant by many experiments, also in prescription corrigent and its dosage selected, discovery when use 2~
One of 6% aspartame, Sucralose, acesulfame potassium, lemon extract, Mint Essence, strawberry essence are a variety of as rectifying
When taste agent, it can make Lurasidone HCl oral disnitegration tablet obtained that there is excellent mouthfeel.
Applicant by many experiments, also in prescription lubricant and its dosage selected, discovery when use 1~
One of 4% silica and magnesium stearate, talcum powder or it is a variety of as lubricant when, can obtain good
Lubricant effect.
Specific embodiment:
For the understanding convenient for technical solution of the present invention, invention is illustrated With reference to embodiment, but this hair
Bright range is not limited only to the range of these embodiments.
Embodiment 1
Prescription: Lurasidone HCl 10mg lactose (carrier) 20mg polyvinylpyrrolidone 2mg lactose 143mg
Microcrystalline cellulose 50mg croscarmellose sodium 17.5mg aspartame 4.5mg Mint Essence 0.5mg is stearic
Sour magnesium 2.5mg
Adhesive solvent: 40% ethanol solution 50mg
Embodiment 2
Prescription: Lurasidone HCl 10mg mannitol composites of starch (carrier) 60mg polyvinylpyrrolidone 4mg
Mannitol 93.5mg microcrystalline cellulose 50mg carboxyrnethyl starch sodium 15mg acesulfame potassium 13mg strawberry essence 2mg talcum powder
2.5mg
Adhesive solvent: 40% ethanol solution 30mg
Embodiment 3
Prescription: Lurasidone HCl 10mg mannitol (carrier) 105mg polyvinylpyrrolidone 6mg starch lactose
Compound 90mg sodium carboxymethyl starch 20mg acesulfame potassium 4mg lemon extract 6mg talcum powder 9mg
Adhesive solvent: 40% ethanol solution 60mg
Embodiment 4
Prescription: Lurasidone HCl 10mg lactose (carrier) 80mg hydroxypropyl methylcellulose 4mg mannitol starch is multiple
Close object 79mg microcrystalline cellulose 50mg crospovidone 12mg acesulfame potassium 8mg lemon extract 2mg magnesium stearate
2.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 80mg
Embodiment 5
Prescription: Lurasidone HCl 20mg mannitol (carrier) 55mg hydroxypropyl methylcellulose 4mg starch lactose is multiple
Close object 89mg microcrystalline cellulose 50mg crospovidone 16mg Sucralose 7mg lemon extract 2mg magnesium stearate
2.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 80mg
Embodiment 6
Prescription: Lurasidone HCl 20mg starch milk saccharide complex (carrier) 90mg polyvinylpyrrolidone 6mg
Starch milk saccharide complex 107.75mg croscarmellose sodium 15mg aspartame 6.25mg talcum powder 5mg
Adhesive solvent: 40% ethanol solution 60mg
Embodiment 7
Prescription: Lurasidone HCl 20mg mannitol (carrier) 60mg hydroxypropyl methylcellulose 6mg mannitol 84mg
Microcrystalline cellulose 50mg crospovidone 18.75mg Sucralose 5mg lemon extract 1.25mg magnesium stearate 2.5mg
Silica 2.5mg
Adhesive solvent: 40% ethanol solution 140mg
Embodiment 8
Prescription: Lurasidone HCl 40mg lactose (carrier) 60mg hydroxypropyl cellulose 6mg mannitol starch is multiple
Close object 114mg sodium carboxymethyl starch 18.75mg Sucralose 5mg lemon extract 1.25mg silica 5mg
Adhesive solvent: 40% ethanol solution 120mg
Embodiment 9
Prescription: Lurasidone HCl 40mg lactose (carrier) 75mg polyvinylpyrrolidone 4mg lactose 51mg
Microcrystalline cellulose 55mg croscarmellose sodium 15mg Sucralose 4.5mg Mint Essence 0.5mg stearic acid
Magnesium 2.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 160mg
Embodiment 10
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 90mg hydroxypropyl cellulose 7mg is sweet
Reveal alcohol composites of starch 49mg microcrystalline cellulose 30mg sodium carboxymethyl starch 20mg acesulfame potassium 8mg strawberry essence 1mg
Silica 2mg talcum powder 3mg
Adhesive solvent: 40% ethanol solution 240mg
Embodiment 11
Prescription: Lurasidone HCl 40mg mannitol composites of starch (carrier) 60mg hydroxypropyl methylcellulose 10mg
Starch milk saccharide complex 58.5mg mannitol 50mg crospovidone 18mg aspartame 5mg strawberry essence 1mg
Magnesium stearate 2.5mg silica 5mg
Adhesive solvent: 40% ethanol solution 240mg
Embodiment 12
Prescription: Lurasidone HCl 40mg mannitol (carrier) 30mg mannitol composites of starch (carrier) 30mg
Hydroxypropyl methylcellulose 4mg microcrystalline cellulose 50mg mannitol 70mg croscarmellose sodium 17.5mg aspa
Smooth 5mg Mint Essence 1mg magnesium stearate 2.5mg
Adhesive solvent: 40% ethanol solution 200mg
Embodiment 13
Prescription: Lurasidone HCl 40mg mannitol (carrier) 60mg hydroxypropyl cellulose 4mg lactose 35mg
Starch milk saccharide complex 35mg microcrystalline cellulose 50mg crospovidone 17.5mg aspartame 5mg Mint Essence 1mg
Magnesium stearate 2.5mg
Adhesive solvent: 40% ethanol solution 280mg
Embodiment 14
Prescription: Lurasidone HCl 20mg mannitol composites of starch (carrier) 40mg hydroxypropyl cellulose 6mg
Mannit S .5mg microcrystalline cellulose 45mg crospovidone 17.5mg acesulfame potassium 8mg lemon extract 1mg is stearic
Sour magnesium 1.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 160mg
Embodiment 15
Prescription: Lurasidone HCl 20mg starch (carrier) 40mg hydroxypropyl cellulose 6mg mannit S .5mg
Microcrystalline cellulose 45mg crospovidone 17.5mg acesulfame potassium 8mg lemon extract 1mg magnesium stearate 1.5mg bis-
Silica 2.5mg
Adhesive solvent: 40% ethanol solution 80mg
Embodiment 16
Prescription: Lurasidone HCl 20mg microcrystalline cellulose (carrier) 40mg hydroxypropyl cellulose 6mg mannitol
108.5mg microcrystalline cellulose 45mg crospovidone 17.5mg acesulfame potassium 8mg lemon extract 1mg magnesium stearate
1.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 80mg
Embodiment 17
Prescription: Lurasidone HCl 20mg lactose (carrier) 10mg polyvinylpyrrolidone 2mg mannitol starch
Compound 140.5mg microcrystalline cellulose 60mg crospovidone 10mg Sucralose 4mg Mint Essence 1mg is stearic
Sour magnesium 2.5mg
Adhesive solvent: 40% ethanol solution 80mg
Embodiment 18
Prescription: Lurasidone HCl 20mg lactose (carrier) 20mg polyvinylpyrrolidone 2mg mannitol starch
Compound 130.5mg microcrystalline cellulose 60mg crospovidone 10mg Sucralose 4mg Mint Essence 1mg is stearic
Sour magnesium 2.5mg
Adhesive solvent: 40% ethanol solution 60mg
Embodiment 19
Prescription: Lurasidone HCl 20mg lactose (carrier) 20mg polyvinylpyrrolidone 1mg lactose 134mg
Microcrystalline cellulose 50mg croscarmellose sodium 17.5mg Sucralose 4mg Mint Essence 1mg magnesium stearate
2.5mg
Adhesive solvent: 40% ethanol solution 60mg
Embodiment 20
Prescription: Lurasidone HCl 20mg starch milk saccharide complex (carrier) 90mg polyvinylpyrrolidone 6mg
Lactose 64.25mg microcrystalline cellulose 42mg croscarmellose sodium 18.75mg aspartame 4mg Mint Essence
1mg magnesium stearate 2.5mg silica 1 .5mg
Adhesive solvent: 40% ethanol solution 80mg
Embodiment 21
Prescription: Lurasidone HCl 20mg mannitol composites of starch (carrier) 120mg hydroxypropyl cellulose 10mg
Mannitol composites of starch 30mg microcrystalline cellulose 30mg sodium carboxymethyl starch 25mg Sucralose 8mg Mint Essence
1mg strawberry essence 1mg magnesium stearate 2.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 40mg
Embodiment 22
Prescription: Lurasidone HCl 20mg mannitol composites of starch (carrier) 120mg hydroxypropyl cellulose 12mg
Mannitol composites of starch 28mg microcrystalline cellulose 30mg sodium carboxymethyl starch 25mg Sucralose 8mg Mint Essence
1mg strawberry essence 1mg magnesium stearate 2.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 100mg
Embodiment 23
Prescription: Lurasidone HCl 20mg mannitol composites of starch (carrier) 130mg hydroxypropyl cellulose 12mg
Mannitol composites of starch 20mg microcrystalline cellulose 30mg sodium carboxymethyl starch 25mg Sucralose 8mg Mint Essence
1mg strawberry essence 1mg magnesium stearate 2.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 140mg
Embodiment 24
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 40mg polyvinylpyrrolidone 8mg
Mannitol 82mg microcrystalline cellulose 50mg crospovidone 18mg aspartame 7mg strawberry essence 0.5mg is stearic
Sour magnesium 1.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 160mg
Embodiment 25
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 40mg methylcellulose 8mg sweet dew
Alcohol 82mg microcrystalline cellulose 50mg crospovidone 18mg aspartame 7mg strawberry essence 0.5mg magnesium stearate
1.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 120mg
Embodiment 26
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 40mg sodium carboxymethylcellulose 8mg
Mannitol 82mg microcrystalline cellulose 50mg crospovidone 18mg aspartame 7mg strawberry essence 0.5mg is stearic
Sour magnesium 1.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 120mg
Embodiment 27
Prescription: Lurasidone HCl 40mg mannitol composites of starch (carrier) 40mg ethyl cellulose 8mg is sweet
Reveal alcohol 82mg microcrystalline cellulose 50mg crospovidone 18mg aspartame 7mg strawberry essence 0.5mg stearic acid
Magnesium 1.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 120mg
Embodiment 28
Prescription: Lurasidone HCl 40mg mannitol composites of starch (carrier) 80mg hydroxypropyl cellulose 7.5mg
Mannitol 98mg crospovidone 10mg acesulfame potassium 8.5mg lemon extract 0.5mg silica 2.5mg talcum powder
3mg
Adhesive solvent: 40% ethanol solution 160mg
Embodiment 29
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 80mg hydroxypropyl cellulose 7.5mg
Mannitol 100mg crospovidone 8mg acesulfame potassium 8.5mg lemon extract 0.5mg silica 2.5mg talcum powder
3mg
Adhesive solvent: 40% ethanol solution 200mg
Embodiment 30
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 80mg hydroxypropyl cellulose 7.5mg
Mannitol 98mg low-substituted hydroxypropyl cellulose 10mg acesulfame potassium 8.5mg lemon extract 0.5mg silica 2.5mg
Talcum powder 3mg
Adhesive solvent: 40% ethanol solution 240mg
Embodiment 31
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 80mg hydroxypropyl methylcellulose 6mg is sweet
Reveal 45 carboxyrnethyl starch sodium 20mg Sucralose 6mg lemon extract 1mg of alcohol composites of starch 49.5mg microcrystalline cellulose
Magnesium stearate 2.5mg
Adhesive solvent: 40% ethanol solution 240mg
Embodiment 32
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 80mg hydroxypropyl methylcellulose 6mg forms sediment
45 carboxyrnethyl starch sodium 20mg Sucralose 6mg lemon extract 1mg magnesium stearate of powder 49.5mg microcrystalline cellulose
2.5mg
Adhesive solvent: 40% ethanol solution 200mg
Embodiment 33
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 60mg polyvinylpyrrolidone 12mg
Starch milk saccharide complex 51.5mg microcrystalline cellulose 65mg croscarmellose sodium 12.5mg aspartame 5mg
Mint Essence 1mg magnesium stearate 1.5mg silica 1 .5mg
Adhesive solvent: 40% ethanol solution 240mg
Embodiment 34
Prescription: Lurasidone HCl 40mg mannitol (carrier) 60mg hydroxypropyl methylcellulose 6mg mannitol
51.5mg microcrystalline cellulose 62.5mg crospovidone 18.75mg aspartame 5mg Mint Essence 1.25mg is hard
Fatty acid magnesium 2.5mg silica 2.5mg
Adhesive solvent: 40% ethanol solution 200mg
Embodiment 35
Prescription: Lurasidone HCl 40mg mannitol (carrier) 90mg hydroxypropyl methylcellulose 6mg mannitol 40mg
Microcrystalline cellulose 50mg crospovidone 12.5mg aspartame 5mg Mint Essence 1.5mg magnesium stearate 2.5mg
Silica 2.5mg
Adhesive solvent: 40% ethanol solution 160mg
Embodiment 36
Prescription: Lurasidone HCl 40mg mannitol (carrier) 40mg hydroxypropyl methylcellulose 6mg mannitol 78mg
Microcrystalline cellulose 72mg crospovidone 18.75mg aspartame 7mg Mint Essence 3.25mg magnesium stearate 2.5mg
Silica 2.5mg
Adhesive solvent: 40% ethanol solution 240mg
Embodiment 37
Prescription: Lurasidone HCl 40mg starch milk saccharide complex (carrier) 90mg hydroxypropyl methylcellulose 7.5mg
Mannitol 83.5mg crospovidone 15mg acesulfame potassium 8mg strawberry essence 1mg silica 2mg talcum powder 3mg
Adhesive solvent: 40% ethanol solution 280mg
Embodiment 38
Prescription: Lurasidone HCl 40mg mannitol (carrier) 70mg hydroxypropyl methylcellulose 4mg microcrystalline cellulose
63mg mannitol 50mg crospovidone 15mg Sucralose 5mg lemon extract 0.5mg magnesium stearate 2.5mg
Adhesive solvent: 40% ethanol solution 200mg
Embodiment 39
Prescription: Lurasidone HCl 60mg mannitol (carrier) 60mg polyvinylpyrrolidone 8mg lactose
54.5mg microcrystalline cellulose 45mg sodium carboxymethylcellulose 15mg aspartame 5mg magnesium stearate 2.5mg
Adhesive solvent: 40% ethanol solution 180mg
Embodiment 40
Prescription: Lurasidone HCl 60mg starch milk saccharide complex (carrier) 80mg hydroxypropyl methylcellulose 10mg is sweet
Reveal alcohol 35mg microcrystalline cellulose 35mg crospovidone 20mg acesulfame potassium 6mg lemon extract 1mg magnesium stearate
1.5mg silica 1 .5mg
Adhesive solvent: 40% ethanol solution 240mg
Embodiment 41
Prescription: Lurasidone HCl 80mg lactose (carrier) 80mg hydroxypropyl methylcellulose 8mg mannitol starch is multiple
Close object 31mg microcrystalline cellulose 30mg croscarmellose sodium 13mg acesulfame potassium 5mg talcum powder 3mg
Adhesive solvent: 40% ethanol solution 320mg
Embodiment 42
Prescription: Lurasidone HCl 80mg starch milk saccharide complex (carrier) 70mg hydroxypropyl cellulose 4mg is sweet
Reveal alcohol 38.5mg microcrystalline cellulose 30mg croscarmellose sodium 20mg acesulfame potassium 5mg talcum powder 3mg
Adhesive solvent: 40% ethanol solution 400mg
Embodiment 43
Prescription: Lurasidone HCl 40mg mannitol (carrier) 80mg hydroxypropyl methylcellulose 5mg microcrystalline cellulose
40.5mg mannitol 54mg crospovidone 22.5mg Sucralose 5mg lemon extract 0.5mg magnesium stearate
2.5mg
Adhesive solvent: 40% ethanol solution 200mg
Embodiment 44
Prescription: Lurasidone HCl 40mg mannitol (carrier) 50mg hydroxypropyl methylcellulose 7.5mg microcrystalline cellulose
Plain 81mg mannitol 42mg crospovidone 20mg Sucralose 5mg lemon extract 0.5mg magnesium stearate
2.5mg
Adhesive solvent: 40% ethanol solution 200mg
。
Claims (26)
1. a kind of Lurasidone HCl oral disnitegration tablet, it is characterised in that by following weight percent at being grouped as: 8~24%
Lurasidone HCl, 8~48% carriers, 0.8~4% adhesive, 24~76.2% fillers, 4~10% disintegrating agents, 2~6%
Corrigent, 1~4% lubricant；The carrier is in lactose, mannitol, starch milk saccharide complex, mannitol composites of starch
It is one or more；Described adhesive is one kind or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone
Kind.
2. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that the weight hundred of each component
Divide ratio are as follows: 12~20% Lurasidone HCls, 12~36% carriers, 1.6~3% adhesives, 38~60% fillers, 6~9%
Disintegrating agent, 2.5~5% corrigents, 1~3% lubricant.
3. Lurasidone HCl oral disnitegration tablet according to claim 2, it is characterised in that the Lurasidone HCl weight
Measuring percentage is 16%.
4. Lurasidone HCl oral disnitegration tablet according to claim 3, it is characterised in that the weight hundred of each component
Divide ratio are as follows: 16% Lurasidone HCl, 24% carrier, 2.4% adhesive, 45.6% filler, 7.5% disintegrating agent, 2.5% rectifys
Taste agent, 2% lubricant.
5. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that the carrier be selected from lactose with
Mannitol.
6. Lurasidone HCl oral disnitegration tablet according to claim 5, it is characterised in that the carrier is mannitol.
7. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that described adhesive is hydroxypropyl first
Cellulose, polyvinylpyrrolidone it is one or more.
8. Lurasidone HCl oral disnitegration tablet according to claim 7, it is characterised in that described adhesive is hydroxypropyl first
Cellulose.
9. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that the filler be selected from lactose,
The combination of mannitol, starch milk saccharide complex, mannitol composites of starch, microcrystalline cellulose.
10. Lurasidone HCl oral disnitegration tablet according to claim 9, it is characterised in that the filler is selected from sweet dew
Alcohol, starch milk saccharide complex one or two kinds of microcrystalline celluloses combination.
11. Lurasidone HCl oral disnitegration tablet according to claim 10, it is characterised in that the filler is sweet dew
The combination of alcohol and microcrystalline cellulose.
12. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that the disintegrating agent is selected from carboxylic first
One of sodium starch, cross-linked carboxymethyl cellulose sodium, crospovidone are a variety of.
13. Lurasidone HCl oral disnitegration tablet according to claim 12, it is characterised in that the disintegrating agent is crosslinking
The one or two of povidone and croscarmellose sodium.
14. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that the corrigent is selected from A Si
One of Pa Tan, Sucralose, acesulfame potassium, lemon extract, Mint Essence, strawberry essence are a variety of.
15. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that the lubricant is selected from dioxy
One of SiClx, magnesium stearate, talcum powder are a variety of.
16. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that the Lurasidone is averaged grain
Diameter is 0.1~10 μm.
17. Lurasidone HCl oral disnitegration tablet according to claim 16, it is characterised in that the Lurasidone is average
Partial size is 0.1~5 μm.
18. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that the D of the diameter of carrier50For
30 μm~200 μm.
19. Lurasidone HCl oral disnitegration tablet according to claim 18, it is characterised in that the D of the diameter of carrier50
It is 75~160 μm.
20. Lurasidone HCl oral disnitegration tablet according to claim 19, it is characterised in that the D of the diameter of carrier50
It is 160 μm.
21. Lurasidone HCl oral disnitegration tablet according to claim 1, it is characterised in that the weight hundred of each component
Divide ratio are as follows: Lurasidone HCl 16%, carrier mannitol 12~36%, hydroxypropyl methylcellulose 1.6~3%, mannitol and crystallite
Cellulose 38~60%, crospovidone 6~9%, corrigent 2.5~5%, lubricant 1~3%；Wherein the hydrochloric acid Shandong is drawn
The average grain diameter of western ketone is 0.1~10 μm, the D of mannitol50It is 75~160 μm.
22. Lurasidone HCl oral disnitegration tablet according to claim 21, it is characterised in that the weight of each component
Percentage are as follows: Lurasidone HCl 16%, carrier mannitol 24%, hydroxypropyl methylcellulose 2.4%, filler mannitol
20.6%, microcrystalline cellulose 25%, crospovidone 7.5%, Sucralose 2%, Mint Essence 0.5%, magnesium stearate 1%,
Silica 1 %；Wherein the average grain diameter of the Lurasidone HCl is 0.1~5 μm, the D of mannitol50It is 160 μm.
23. Lurasidone HCl oral disnitegration tablet described in any one of -22 according to claim 1, it is characterised in that described
Preparation method are as follows: Lurasidone HCl is suspended in binder solution, drug containing suspension is made, then will contained by fluidized bed
Medicine suspension be wrapped in by spraying on carrier formed carry medicine particle, add remaining auxiliary material be uniformly mixed, tabletting to obtain the final product.
24. the Lurasidone HCl oral disnitegration tablet according to claim 23, it is characterised in that described adhesive solution
It is made for adhesive to be dissolved in solvent；The solvent is the mixed solvent of ethyl alcohol and water composition；The ethyl alcohol and water form
Mixed solvent concentration be 10%~45%；The weight ratio of described adhesive solution and Lurasidone HCl is 3:1~8:1.
25. the Lurasidone HCl oral disnitegration tablet according to claim 24, it is characterised in that described adhesive solution
It is made for adhesive to be dissolved in solvent；The solvent is the mixed solvent of ethyl alcohol and water composition；The ethyl alcohol and water form
Mixed solvent concentration be 40%；The weight ratio of described adhesive solution and Lurasidone HCl is 5:1.
26. Lurasidone HCl oral disnitegration tablet described in any one of -22 according to claim 1, it is characterised in that described
Steps are as follows for the preparation method of Lurasidone HCl oral disnitegration tablet: (1) recipe quantity hydroxypropyl methylcellulose being taken to be dissolved in suitable second
In the mixed solution of alcohol and water, the Lurasidone HCl for weighing recipe quantity is added in above-mentioned solution, and it is mixed that drug containing is made in mechanical stirring
The drug containing suspension is sprayed by fluidized bed by bottom material of carrier by suspension, is wrapped up, dry, is made and is carried medicine particle；(2) step is taken
Suddenly load medicine particle, recipe quantity filler obtained by (1) cross 50 meshes, and recipe quantity disintegrating agent, corrigent, lubricant is taken to cross 65 mesh
Sieve, by after sieving remove lubricant all auxiliary materials be uniformly mixed, then plus mix lubricant it is uniform, tabletting to obtain the final product.
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| CN108926541A (en) * | 2017-05-26 | 2018-12-04 | 万全万特制药（厦门）有限公司 | Ziprasidone oral disintegrating tablet and preparation method thereof |
| CN107854446A (en) * | 2017-12-19 | 2018-03-30 | 佛山市弘泰药物研发有限公司 | A kind of Lurasidone HCl oral disintegrating tablet and preparation method thereof |
| CN115715766A (en) * | 2018-09-03 | 2023-02-28 | 正大天晴药业集团股份有限公司 | Solid pharmaceutical composition comprising 1,3,5-triazine derivative or salt thereof |
| CN110833532A (en) * | 2019-12-19 | 2020-02-25 | 赵洁 | Rapidly-released lurasidone hydrochloride tablet and preparation process thereof |
| AT17300U3 (en) * | 2020-12-03 | 2022-02-15 | G L Pharma Gmbh | Solid oral pharmaceutical composition |
| WO2023080854A1 (en) * | 2021-11-03 | 2023-05-11 | Santa Farma Ilac Sanayii A.S. | Lurasidone hydrochloride compositions |
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| CN103054824A (en) * | 2012-12-21 | 2013-04-24 | 北京万全德众医药生物技术有限公司 | Lurasidone hydrochloride orally-disintegrating tablet preparation and preparation method thereof |
| CN103536568A (en) * | 2012-07-12 | 2014-01-29 | 成都康弘药业集团股份有限公司 | Orally disintegrating tablets containing lurasidone and preparation method thereof |
| CN103751139A (en) * | 2013-12-31 | 2014-04-30 | 北京万全德众医药生物技术有限公司 | Lurasidone orally disintegrating tablet |
| CN104337790A (en) * | 2014-11-02 | 2015-02-11 | 石家庄四药有限公司 | Lurasidone hydrochloride oral preparation and preparing method of lurasidone hydrochloride oral preparation |
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|---|---|---|---|---|
| CN103536568A (en) * | 2012-07-12 | 2014-01-29 | 成都康弘药业集团股份有限公司 | Orally disintegrating tablets containing lurasidone and preparation method thereof |
| CN103054824A (en) * | 2012-12-21 | 2013-04-24 | 北京万全德众医药生物技术有限公司 | Lurasidone hydrochloride orally-disintegrating tablet preparation and preparation method thereof |
| CN103751139A (en) * | 2013-12-31 | 2014-04-30 | 北京万全德众医药生物技术有限公司 | Lurasidone orally disintegrating tablet |
| CN104337790A (en) * | 2014-11-02 | 2015-02-11 | 石家庄四药有限公司 | Lurasidone hydrochloride oral preparation and preparing method of lurasidone hydrochloride oral preparation |
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