CN102462679A - Iloperidone medicinal oral preparation and preparation method thereof - Google Patents
Iloperidone medicinal oral preparation and preparation method thereof Download PDFInfo
- Publication number
- CN102462679A CN102462679A CN2010105449502A CN201010544950A CN102462679A CN 102462679 A CN102462679 A CN 102462679A CN 2010105449502 A CN2010105449502 A CN 2010105449502A CN 201010544950 A CN201010544950 A CN 201010544950A CN 102462679 A CN102462679 A CN 102462679A
- Authority
- CN
- China
- Prior art keywords
- iloperidone
- preparation
- grams
- microns
- raw material
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of medicinal preparations containing organic active ingredients, in particular to an iloperidone medicinal oral preparation and a preparation method thereof. The iloperidone medicinal oral preparation comprises iloperidone, a filler, a disintegrant, a lubricant, a glidant and a binder, wherein the iloperidone reaches extra fine particle diameters through special treatment; 90 percent of the particle diameters is below 25 micrometers and 99 percent of the particle diameters is below 45 micrometers; and the distribution of the particle diameters is narrower, so that the dissolubility, the stability, the dissolution amount and the dissolution speed of the medicinal preparation are greatly increased; and the iloperidone medicinal oral preparation can be effectively and rapidly released without adding any cosolvent, so the bioavailability of the preparation is greatly improved, and the iloperidone medicinal oral preparation is suitable for mass production.
Description
Technical field
The present invention relates to contain the pharmaceutical product technical field of organic effective ingredient, be specially iloperidone oral formulations and preparation method thereof.
Background technology
Along with the development of society, the pressure of people's life and work is increasing, and increasing people receives the puzzlement of spirit type disease, brings greatly burden for society and family.According to statistics, the whole world has 400,000,000 people to suffer from spirit type disease in various degree approximately at present, and this disease has become first of the world's ten big kinds of Diseases.Spirit type disease is the same with cardiovascular and cerebrovascular vessel, respiratory system disease and malignant tumor, becomes one of several big diseases occurred frequently of China.Understand according to investigations, China psychotic has 1,600 ten thousand people approximately, and the sickness rate of spirit type disease is in rising trend at home, has every year 250000 people to die from suicide approximately.Schizophrenia is the highest a kind of of prevalence in the mental sickness, and the sickness rate in city is apparently higher than the rural area.According to statistics, China's schizophrenia prevalence reaches 6.55%, and the patient has 7,800,000 more than.Schizophrenia is a kind ofly to be separated with ergasia and actual environment; Cognitive process, affective process, inharmonious mutually, the mutual splitted characteristic symptom of will process are outstanding behaviours, and also reflect the psychosis of other symptoms of " division " characteristic to a certain extent with hallucination, vain hope, tension syndrome etc.The market of antischizophrinic thing (call in the following text anti-smart divide medicine) is through for many years exploitation, and is quite ripe.2006, the anti-smart sales volume of medicine in the world market of dividing reached 16,200,000,000 dollars, becomes global the fifth-largest medicine classification.
At present; " atypiaization " of psychosis medication becomes clear day by day; By 2008, the whole world had 13 atypical antipsychotic listings, wherein has 7 to go on the market in China; Be respectively gone on the market clozapine for many years and the Paliperidone that goes on the market recently, and olanzapine, risperidone, Quetiapine, Aripiprazole and Ziprasidone.In China; Atypical antipsychotic has become a clinical line medication in recent years; The sales volume of risperidone, olanzapine, Quetiapine, Aripiprazole and Ziprasidone five big kinds has accounted for 95% of domestic psychosis prescription drug market; This 5 big kind strides into " cookle " rank every year 2008, global annual sales amount reached 46.9 hundred million, 34.4 hundred million, 44.5 hundred million, 21.5 hundred million and 10.1 hundred million dollars respectively in 2008.At home, 5 big kind sample hospital gross sales amounts also reach 2.876 hundred million yuan, account for 96.6% of psychosis market, and the annual rate of growth in 2008 73.6% of 5 big kinds also become the primary factor of antipsychotic drug rapid growth.
But; Although the safety of medicine significantly improves; But still there are some problems in existing atypical psychosis medicine; As be difficult to radical curing of disease, need take medicine for a long time even all the life,, drug withdrawal easy relapse not good enough or the like for severe mental sickness effect of drugs, therefore, the research of industry expectation psychosis medicine novel form, novel targets etc. can have bigger breakthrough.Iloperidone (Iloperidone) is schizoid first gene target property medicine of treatment, and iloperidone has carried out 35 III phase clinical researches, and sum surpasses 3000 people, and III phase clinical research confirmation iloperidone has better curative effect.Develop this medicine and will bring good economic benefit and market prospect.
Yi Panli ketone is that structural formula is following between the crystalline powder of white or off-white color:
Molecular formula: C
24H
27FN
2O
4, molecular weight: 426.48, can not be water-soluble, the atomic 0.1mol/l hydrochloric acid that is dissolved in is prone to be dissolved in chloroform, ethanol, methanol, acetonitrile.Because the chemical property of iloperidone defines iloperidone onset immediately, stripping is difficult to solve, and has greatly limited the iloperidone bioavailability; The preparation of listing is that specification is respectively 1mg, 2mg, 4mg, 6mg, 8mg, 10mg, 12mg at the conventional tablet of U.S.'s listing at present, and the inventor finds that through the listing preparation is investigated the said preparation stripping is very fast; It is thus clear that solved this difficult problem of stripping difficulty abroad, to domestic crude drug, the inventor is through attempting; According to the adjuvant of external listing preparation is lactose one water and thing, microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel, magnesium stearate; Take hypromellose, wet granulation carries out common technology tabletting; Outward appearance is good, but can't reach the fast requirement of its stripping at all.The preparation that possibly abroad go on the market has been taked special technology, does not just embody at all.
One Chinese patent application number is a CN201010184547.3 (title: a kind of Iloperidone drug composition and preparation method thereof; Applicant: Beijing DeZhong Wanquan Pharmaceutical Technology Co., Ltd; In please day: also mention in order to improve result of extraction in the patent application document on May 27th, 2010); The method of having mentioned micronization processes iloperidone raw material increases stripping, and the iloperidone raw material particle size scope of qualification is below 75 microns, just below 200 orders.Through inventor's experiment, general pulverizing can reach this particle diameter below 200 orders, takes the method among the patent application CN201010184547.3; Particle diameter is micronized to below 75 microns; And the most preferred embodiment according to embodying in the patent application document experimentizes, and the result is investigated, even in preparation, added cosolvent; The result does not reach the corresponding result of extraction of listing preparation; And the mode that the elution test method of this invention indicates on the net with U.S. FDA not～cause, can not show as concordance so stripping discharges the same city of result preparation, the stripping investigation method among the patent application CN201010184547.3 adopts quantity of solvent more; Be almost a times of solvent in U.S.'s listing preparation elution test method that U.S. FDA shows on the net; And rotating speed is faster, although so the stripping result of patent application CN201010184547.3 in its patent, embody relatively good, if down more at all can't be consistent with the preparation stripping curve that goes on the market at equal testing conditions; And through the present invention's confirmation, its preparation stripping curve that goes on the market relatively is slower.
In order to reach and the approaching result of extraction of external listing preparation, the inventor has taked the raw material iloperidone is carried out the mode of special handling, utilizes high pressure draught to pulverize the mode of crude drug having been carried out comminution by gas stream; Filter out an only particle size distribution simultaneously; Make iloperidone crude drug particle size distribution littler,, thereby greatly solved this difficult problem then according to common preparation process pelletizing press sheet or encapsulating capsule; Under the situation that does not add any cosolvent; Through with the contrast of external listing preparation, reached and the immediate releasing effect of listing preparation, stripping curve is approaching; Bioavailability is improved greatly, in clinical practice, reached and the approaching effect of listing preparation.
Technology of the present invention is simple, is easy to amplify, and is fit to large-scale production.
Summary of the invention
The purpose of this invention is to provide a kind of stripping discharges fast; Preparation technology is simple, is fit to the pharmaceutical preparation that the schizophrenia patient takes, and is mainly tablet and hard capsule; Overcome stripping and discharged the problem slow, that bioavailability is low; Not only stripping is rapid, and bioavailability is high, and suitable suitability for industrialized production.
Iloperidone drug oral preparation according to the invention comprises 90% particle diameter below 25 microns, and 99% particle diameter is at the iloperidone below 45 microns.
The dosage form of the drug oral of iloperidone described in the present invention preparation is tablet or hard capsule.
The composition and the quality proportioning of the iloperidone drug oral preparation described in the present invention are: iloperidone 0.2%～20%, filler 10～96% disintegrating agents 0.1～10%, lubricant 0～3%, fluidizer 0～3%, bonding agent 0～10%.
Further, said filler is one or several the compositions in lactose, starch, microcrystalline Cellulose, mannitol, the hyprolose.Said lubricant is a kind of in magnesium stearate, stearic acid, fumaric acid stearic acid, the Pulvis Talci or two kinds.Said fluidizer is micropowder silica gel.Said disintegrating agent is one or more the compositions in carboxymethyl starch sodium, polyvinylpolypyrrolidone, the cross-linking sodium carboxymethyl cellulose.Said bonding agent is a kind of in hypromellose, starch, polyvidone, the sodium carboxymethyl cellulose.
The complete time of stripping of iloperidone drug oral preparation according to the invention is 30 seconds～15 minutes.
At present the preparation of listing is a conventional tablet in the iloperidone world wide, U.S.'s listing be the common disk of commodity " FANAPT " by name, specification is respectively 1mg, 2mg, 4mg, 6mg, 8mg, 10mg, 12mg.Through the inventor listing 12mg specification preparation is investigated discovery; The stripping of this listing preparation is very fast; Just can reach 60% in 2 minutes discharges; Just can reach complete stripping in 15 minutes, better curative effect is arranged in clinical practice, very big relation arranged and the stripping of these good curative effects and this listing preparation is rapid, bioavailability is high.Merely rely on the help of adjuvant can not solve stripping problem slowly fully; In order to address this problem; We have adopted the iloperidone raw material through high pressure draught pulverizing carrying out micronization; And filter out only particle size distribution range: 90% below 25 microns, and 99% below 45 microns, thereby improved the stripping and the dissolution rate of preparation greatly.
Operate by following technology then: the micronization raw material that will handle takes by weighing recipe quantity; The filler, the disintegrating agent mix homogeneously that add recipe quantity again; Add bonding agent and carry out wet granulation; Carry out tabletting or encapsulating capsule after adding the lubricant, fluidizer mix homogeneously of recipe quantity again, in the technology of tabletting, also can take not make the granule direct compression, in the particulate process of preparation, also can take to divide the mode that adds to carry out tabletting inside and outside the disintegrating agent.
Inquire about through the inventor; Among the one Chinese patent application CN201010184547.3 in order to improve result of extraction; The method of also having mentioned micronization processes iloperidone raw material increases stripping, and the iloperidone raw material particle size scope of its qualification is below 75 microns, just below 200 orders.Through inventor's experiment confirm; General pulverizing can reach this particle diameter below 200 orders; And take the method among the CN201010184547.3, particle diameter is micronized to below 75 microns, and experimentizes according to the most preferred embodiment that embodies in the patent; Even in preparation, added cosolvent, the result does not reach the listing corresponding result of extraction of preparation (seeing attached list 1).And,,,, can not reach too with the approaching dissolution rate of preparation that gone on the market even add cosolvent if with the preparation of particle size distribution 90% in the iloperidone feedstock production more than 25 microns with the raw material micronization through inventor's confirmation.In order to reach the similar result of extraction of the same city preparation, the present invention has carried out special high pressure gas fluidisation with raw material and has handled, and to have screened particle size range be 90% to be below 25 microns, and 99% at the active component of the iloperidone below 45 microns as preparation.
For the iloperidone oral formulations that confirms to make among the present invention can reach ideal effect, the result to be estimated, the main foundation of evaluation is the investigation that stripping discharges.Inquire about through the inventor; At the tablet of U.S.'s listing, through showing that at the online declaration material of FDA the dissolving-out method of said preparation is according to second appendix XC of 2010 editions versions of Chinese Pharmacopoeia stripping algoscopy, second method; With 500ml; 0.1NHCl be dissolution medium, rotating speed is 50 rev/mins, wherein specification below 4mg with 100ml; 0.1NHCl, carry out the investigation of stripping curve sampling in 2 minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, 60 minutes respectively for the dissolution medium rotating speed is 50 rev/mins.Because each embodiment elution test method is with 900ml among the CN201010184547.3; 0.1NHCl be dissolution medium; Rotating speed is 75 rev/mins, and solvent is more, and rotary speed is faster; Although in this detection method, can discharge basically, just seem that according to the detection method of U.S. listing preparation some is slow.
Consistent for as much as possible with the listing preparation; The disk that the inventor has bought listing preparation " FANAPT " 12mg specification compares, through to stripping among each embodiment the same city preparation of the present invention and the Chinese patent CN201010184547.3 the most rapidly among embodiment 6 and the CN201010184547.3 this inventor with reference to the embodiment 1 of listing preparation prescription to have carried out the contrast of stripping curve.The result sees attached list 1.
Simultaneously the outward appearance of tablet and capsule outward appearance, mobility of particle, uniformity of dosage units are carried out integrated survey, have confirmed the quality of outward appearance by following standard:
Outward appearance mainly waits and takes all factors into consideration from surface smoothness, broken brittleness: excellently do ++ ++, very do +++, be generally ++, difference for+
The result shows: present composition outward appearance can reach requirement; And improved the dissolution rate of iloperidone oral formulations greatly; Through contrast stripping curve and listing preparation basically identical; Stripping than each embodiment that embodies among the one Chinese patent application CN201010184547.3 is rapider, makes medicine onset rapidly in vivo to let clinical effectiveness improve.
The specific embodiment:
Embodiment 1
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, lactose monohydrate 220 grams, microcrystalline Cellulose 110 grams, the polyvinylpolypyrrolidone 12 gram mix homogeneously of handling by 1000 amounts; Add 5% hypromellose and prepare wet granular as binding agent in right amount; Oven dry adds magnesium stearate 2 grams, micropowder silica gel 2 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 350mg.
Hardness: 7.2kg
Outward appearance: ++ ++
Embodiment 2
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, starch 150 grams, microcrystalline Cellulose 180 grams, the carboxymethyl starch sodium 18 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 10% starch slurry prepares wet granular as binding agent in right amount; Oven dry adds magnesium stearate 4 grams, micropowder silica gel 2 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 356mg.
Hardness: 5.8kg
Outward appearance: +++
Embodiment 3
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 0.6 gram, lactose 60 grams, microcrystalline Cellulose 100 grams, the polyvinylpolypyrrolidone 3 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 5% (W/V) hypromellose aqueous solution prepares wet granular as binding agent in right amount; Oven dry adds magnesium stearate 4 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 170mg.
Hardness: 9.1kg
Outward appearance: ++ ++
Embodiment 4
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, hyprolose 100 grams, microcrystalline Cellulose 110 grams, starch 10 grams, the polyvinylpolypyrrolidone 10 gram mix homogeneously of handling by 1000 amounts; Adding concentration is 5% (W/V) polyvidone alcoholic solution, prepares wet granular as binding agent in right amount, oven dry; Add magnesium stearate 6 grams, micropowder silica gel 2 gram mix homogeneously behind the granulate; Tabletting, pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 236mg.
Hardness: 6.5kg
Outward appearance: +++
Embodiment 5
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, mannitol 20 grams, starch 20 grams, microcrystalline Cellulose 180 grams, the polyvinylpolypyrrolidone 12 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 5% (W/V) hypromellose aqueous solution prepares wet granular as binding agent in right amount; Oven dry adds magnesium stearate 2 grams, micropowder silica gel 2 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 239mg.
Hardness: 6.4kg
Outward appearance: ++
Embodiment 6
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 5 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, starch 20 grams, microcrystalline Cellulose 250 grams, the polyvinylpolypyrrolidone 10 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 5% (W/V) hypromellose prepares wet granular as binding agent in right amount; Oven dry adds magnesium stearate 2 grams, micropowder silica gel 2 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 286mg.
Hardness: 6.0kg
Outward appearance: ++
Embodiment 7
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, lactose monohydrate 220 grams, microcrystalline Cellulose 110 grams, the polyvinylpolypyrrolidone 12 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 5% (W/V) hypromellose aqueous solution prepares wet granular as binding agent in right amount; Oven dry adds Pulvis Talci 6 grams, micropowder silica gel 2 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 352mg.
Hardness: 6.7kg
Outward appearance: +++
Embodiment 8
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 0.1 gram, lactose 2 grams, microcrystalline Cellulose 30 grams, the polyvinylpolypyrrolidone 1 gram mix homogeneously of handling by 1000 amounts; Add suitable quantity of water or ethanol and prepare wet granular as binding agent; Oven dry adds magnesium stearate 0.16 gram, micropowder silica gel 0.16 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 35mg.
Hardness: 6.5
Outward appearance: +++
Embodiment 9
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 0.1 gram, lactose monohydrate 100 grams, microcrystalline Cellulose 50 grams, the polyvinylpolypyrrolidone 5 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 5% (W/V) hypromellose aqueous solution prepares wet granular as binding agent in right amount; Oven dry; Add magnesium stearate 1 gram, micropowder silica gel 1 gram mix homogeneously behind the granulate, encapsulating capsule, every about 158mg.
Outward appearance: +++
Embodiment 10
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, starch 220 grams, microcrystalline Cellulose 110 grams, the polyvinylpolypyrrolidone 12 gram mix homogeneously of handling by 1000 amounts; Dry method system granule behind the mix homogeneously; Add magnesium stearate 2 grams, micropowder silica gel 2 gram mix homogeneously again; Tabletting, pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 348mg.
Hardness: 5.8kg
Outward appearance: ++
Embodiment 11
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, starch 50 grams, microcrystalline Cellulose 210 grams, the polyvinylpolypyrrolidone 5 gram mix homogeneously of handling by 1000 amounts; Add magnesium stearate 10 grams, micropowder silica gel 5 gram mix homogeneously behind the mix homogeneously; Direct compression; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 282mg.
Hardness: 6.7kg
Outward appearance: ++
Embodiment 12
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, lactose monohydrate 220 grams, microcrystalline Cellulose 110 grams, the polyvinylpolypyrrolidone 4 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 5% hypromellose prepares wet granular as binding agent in right amount; Oven dry adds polyvinylpolypyrrolidone 3g, magnesium stearate 2 grams, micropowder silica gel 2 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 339mg.
Hardness: 7.5kg
Outward appearance: +++
Embodiment 13
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, lactose monohydrate 220 grams, microcrystalline Cellulose 110 grams, the cross-linking sodium carboxymethyl cellulose 10 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 10% (W/V) starch slurry prepares wet granular as binding agent in right amount; Oven dry adds magnesium stearate 4 grams, micropowder silica gel 2 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 346mg.
Hardness: 6.3kg
Outward appearance: ++ ++
Embodiment 14
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 15 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, lactose 3 grams, microcrystalline Cellulose 40 grams, the polyvinylpolypyrrolidone 1 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 5% (W/V) hypromellose prepares wet granular as binding agent; Oven dry adds magnesium stearate 0.16 gram, micropowder silica gel 0.16 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 46mg.
Hardness: 9.0kg
Outward appearance: ++
Embodiment 15
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 25 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 1.2 grams, lactose monohydrate 200 grams, starch 20 grams, microcrystalline Cellulose 110 grams, the cross-linking sodium carboxymethyl cellulose 10 gram mix homogeneously of handling by 1000 amounts; Adding concentration is that 5% (W/V) hypromellose aqueous solution prepares wet granular as binding agent in right amount; Oven dry adds Pulvis Talci 4 grams, fumaric acid stearic acid 1 gram, micropowder silica gel 1 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 346mg.
Hardness: 6.6kg
Outward appearance: ++ ++
Embodiment 16
With the iloperidone raw material through comminution by gas stream, make particle size distribution range more than 90% less than 5 microns,, subsequent use more than 99% less than 45 microns.Take by weighing iloperidone raw material 0.1 gram, lactose 3 grams, microcrystalline Cellulose 30 grams, the polyvinylpolypyrrolidone 3 gram mix homogeneously of handling by 1000 amounts; Add ethanol and prepare wet granular as binding agent; Oven dry adds fumaric acid stearic acid 0.32 gram mix homogeneously, tabletting behind the granulate; Pressure is controlled at 4.5kg～10kg, every agreement that contracts a film or TV play to an actor or actress 38mg.
Hardness: 6.7kg
Outward appearance: ++ ++
Subordinate list 1
Stripping discharges investigates the result
Claims (6)
1. the drug oral preparation that active component is an iloperidone is characterized in that, said preparation comprises 90% particle diameter at the iloperidone below 25 microns.
2. iloperidone drug oral preparation according to claim 1 is characterized in that the particle diameter 99% of iloperidone is less than 45 microns.
3. iloperidone drug oral preparation according to claim 2 is characterized in that its dosage form is tablet or hard capsule.
4. iloperidone drug oral preparation according to claim 2; It is characterized in that the composition of said preparation and quality proportioning are: iloperidone 0.2%--20%, filler 10～96% disintegrating agents 0.1～10%, lubricant 0～3%, fluidizer 0～3%, bonding agent 0-10%.
5. iloperidone drug oral preparation according to claim 2 is characterized in that, the complete time of said preparation stripping is 30 seconds～15 minutes.
6. according to the described iloperidone drug oral of the arbitrary claim of claim 1 to 5 preparation; It is characterized in that; Its preparation technology is following: earlier iloperidone is carried out micronization through modes such as comminution by gas stream, through detecting, it is subsequent use to make particle diameter reach said requirement back; Take by weighing the iloperidone of recipe quantity then, and other adjuvants of recipe quantity are accomplished follow-up technology.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010544950.2A CN102462679B (en) | 2010-11-15 | 2010-11-15 | A kind of iloperidone drug oral preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010544950.2A CN102462679B (en) | 2010-11-15 | 2010-11-15 | A kind of iloperidone drug oral preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102462679A true CN102462679A (en) | 2012-05-23 |
| CN102462679B CN102462679B (en) | 2015-09-30 |
Family
ID=46066990
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010544950.2A Active CN102462679B (en) | 2010-11-15 | 2010-11-15 | A kind of iloperidone drug oral preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102462679B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102784115B (en) * | 2012-07-13 | 2017-09-26 | 浙江华海药业股份有限公司 | oral tablet containing iloperidone and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101822674A (en) * | 2010-05-27 | 2010-09-08 | 北京德众万全医药科技有限公司 | Iloperidone drug composition and preparation method thereof |
| CN101822673A (en) * | 2009-03-04 | 2010-09-08 | 北京德众万全药物技术开发有限公司 | Iloperidone-containing solid medicinal composition |
| CN102440971A (en) * | 2010-10-15 | 2012-05-09 | 重庆市力扬医药开发有限公司 | Iloperidone orally disintegrating tablet |
-
2010
- 2010-11-15 CN CN201010544950.2A patent/CN102462679B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101822673A (en) * | 2009-03-04 | 2010-09-08 | 北京德众万全药物技术开发有限公司 | Iloperidone-containing solid medicinal composition |
| CN101822674A (en) * | 2010-05-27 | 2010-09-08 | 北京德众万全医药科技有限公司 | Iloperidone drug composition and preparation method thereof |
| CN102440971A (en) * | 2010-10-15 | 2012-05-09 | 重庆市力扬医药开发有限公司 | Iloperidone orally disintegrating tablet |
Non-Patent Citations (1)
| Title |
|---|
| 欧阳宇: "采用气流粉碎提高卡马西平胶囊剂溶出度", 《广东药学》, vol. 9, no. 4, 31 December 1999 (1999-12-31), pages 38 - 39 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102784115B (en) * | 2012-07-13 | 2017-09-26 | 浙江华海药业股份有限公司 | oral tablet containing iloperidone and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102462679B (en) | 2015-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2009542647A (en) | Memantine pharmaceutical composition | |
| KR101977785B1 (en) | Composite formulation for oral administration comprising ezetimibe and rosuvastatin and a process for the preparation thereof | |
| AU2010274589A1 (en) | Oral pharmaceutical composition of rasagiline and process for preparing thereof | |
| CN106580960A (en) | Preparation method of vildagliptin and metformin hydrochloride compound preparation | |
| CN103372014B (en) | A kind of energy Fast Stripping, stable Vardenafil hydrochloric acid oral solid formulation and preparation method thereof | |
| CN102600132A (en) | Oral preparation containing amisulpride | |
| CN104546686A (en) | Mosapride citrate co-grinded product, preparation method thereof and medicine composition containing mosapride citrate co-grinded product | |
| EP2645994B1 (en) | Formulations comprising methylthioninium chloride | |
| WO2012027968A1 (en) | Panaxatriol saponins enteric pellet, capsule comprising same and method for preparing same | |
| CN103263395A (en) | Telmisartan tablet preparation and preparation method thereof | |
| CN103191114A (en) | Moxifloxacin-containing oral drug solid preparation and preparation method thereof | |
| WO2023213878A1 (en) | Solid tablet dosage form of ridinilazole | |
| CN102462679B (en) | A kind of iloperidone drug oral preparation and preparation method thereof | |
| KR101587140B1 (en) | Capsule containing mini-tablets comprising mosapride citrate for sustained-releasing formulation improving gastrointestinal disease and preparing the method thereof | |
| US20220226249A1 (en) | Solid tablet dosage form of ridinilazole | |
| CN102218071A (en) | Micronized deflazacort oral preparation and preparation method thereof | |
| JP7448275B2 (en) | Orbit Azin Fumarate Enteric Coated Pellets, Method of Preparation and Use thereof | |
| CN102727496A (en) | Compound antituberculosis drug oral solid preparation and its preparation method | |
| CN102614140B (en) | Iloperidone oral cavity disintegration tablet and preparation method thereof | |
| CN101897678B (en) | Sustained-release composition of cefaclor | |
| CN103720672B (en) | Montelukast sodium chewable tablet and direct powder compression preparation method thereof | |
| CN109381441B (en) | Huperzine A sustained-release pellet coated granule, sustained-release pellet tablet and preparation method thereof | |
| CN104000821B (en) | Oral double-layer tablet containing telmisartan and amlodipine besylate and preparation method thereof | |
| WO2023173460A1 (en) | Pharmaceutical composition of sglt-2 inhibitor | |
| CN104127390B (en) | A kind of Domperidone Tablets and preparation technology thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 310018 room 103, first floor, building 2, Heke science and technology center, No. 500 QiaoXin Road, Xiasha street, Hangzhou Economic and Technological Development Zone, Zhejiang Province Patentee after: Zhejiang Jiuzhou biomedical Co.,Ltd. Address before: 318000 5th floor, building 4, No. 88, Jiangling Road, Hangzhou, Zhejiang Patentee before: ZHEJIANG JIUZHOU PHARMA SCIENCE & TECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20211027 Address after: 318000 No. 58 Binhai Road, Jiaojiang District, Taizhou City, Zhejiang Province Patentee after: Zhejiang Siwei Pharmaceutical Technology Co.,Ltd. Address before: 310018 room 103, first floor, building 2, Heke science and technology center, No. 500 QiaoXin Road, Xiasha street, Hangzhou Economic and Technological Development Zone, Zhejiang Province Patentee before: Zhejiang Jiuzhou biomedical Co.,Ltd. |