CN102805745B - Iloperidone composition and preparation method thereof - Google Patents
Iloperidone composition and preparation method thereof Download PDFInfo
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- CN102805745B CN102805745B CN201110145252.XA CN201110145252A CN102805745B CN 102805745 B CN102805745 B CN 102805745B CN 201110145252 A CN201110145252 A CN 201110145252A CN 102805745 B CN102805745 B CN 102805745B
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Abstract
The invention relates to an iloperidone composition and a preparation method thereof. According to the iloperidone composition, iloperidone which is taken as an active ingredient is pretreated, so that the particle size of the iloperidone is minimized; and therefore, the dissolution rate of the iloperidone is effectively increased.
Description
Technical field
The present invention relates to a kind of antischizophrenic pharmaceutical composition, particularly relate to a kind of pharmaceutical composition containing iloperidone and preparation method thereof.
Background technology
Schizophrenia is a kind of disease being split into feature with cognitive power and emotional depth, shows as the most basic behavior of men and is affected, such as language, thinking, consciousness and self-perception etc.The scope that the symptom of this disease comprises is comparatively wide, and modal is the obstacle of spiritual aspect, such as hallucinates, paranoea and illusion etc.
Iloperidone is not only while the effective treatment schizophrenia positive symptom (hallucination, vain hope, disturbance in thinking, be hostile to, suspect, behavior is strange), reduce Extra Pyramidal Syndrome (extra pyramidal syndrome, EPS) generation, and negative symptoms of schizophrenia (flat, the social withdrawal of bradykinesia, emotion and language and lack attention) can be improved.
The structure of iloperidone (iloperidone) the earliest by European patent EP 402644 in nineteen ninety December 19 days open.Molecular formula is C
24h
27fN
2o
4, structural formula is as follows:
Chinese patent CN 1578664A (on February 9th, 2005 discloses) and division CN101912367A thereof (December disclosed on the 15th in 2010) discloses the depot formulation of iloperidone and polymer formation, to realize the Co ntrolled release of iloperidone within 2-6 week, for long-acting antipsychotic.Also be a kind of controlled release preparation disclosed in CN101553211A (on October 7th, 2009 is open), medicine formed solid dispersion in solubilizing polymers, the effective blood drug concentration of at least 18 hours is provided; It is also the depot formulation of iloperidone disclosed in WO2004006886 (on January 22nd, 2004 is open).WO2010011232 (on January 28th, 2010 is open) discloses a kind of atypical antipsychotic agents, comprises iloperidone, the compositions formed with succinic acid, fumaric acid, to realize the controlled release release of medicine.
All long-acting controlled release preparations of iloperidone disclosed in above-mentioned patent.
In May, 2009, iloperidone Pian Huo U.S. food Drug Administration (FDA) approval listing, trade name
for schizoid acute treatment of being grown up, specification is 1mg, 2mg, 4mg, 6mg, 8mg, 10mg, 12mg.Adjuvant is lactose monohydrate, microcrystalline Cellulose, hydroxypropyl methylcellulose thing, polyvinylpolypyrrolidone, magnesium stearate, micropowder silica gel and pure water (evaporating in preparation process), adopts wet granulation, then tabletting.According to clinical and
the result of study of itself, requires that in this product, iloperidone dissolution should, more than 90%, should need discharge and reach blood drug level rapidly more than during 80%, 30min at 15min; After oral, 2 ~ 4h reaches Cmax; The relative bioavailability compared with oral administration solution is 96%.
Iloperidone is a kind of crystalline powder, and almost insoluble in water, in the HCl of 0.1N, dissolubility is also very little.Therefore want to meet the requirement that medicine discharges fast, iloperidone must be made the pharmaceutical preparation with good Dissolution behaviours.
As mentioned above,
description discloses its prescription various adjuvants used, and can infer thus and use wet granulation, the present inventor, according to the adjuvant disclosed in it, adopts wet granulation, repeatedly adjust the consumption of various adjuvant, but the iloperidone tablet obtained all fails to obtain
stripping result disclosed in description, only has about 60% after dissolution during 30min.(dissolution determination adopt be the iloperidone sheet leaching condition that FDA provides: paddle method 50rpm, 37 DEG C, with 500ml 0.1NHCl for dissolution medium.)
Visible, even if when not knowing its consumption being clearly aware of various supplementary product kind, it is extremely difficult for going for gratifying iloperidone tablet.
Chinese patent CN101822673A and CN101822674A (being JIUYUE in 2010 to disclose for 8th) discloses iloperidone micronization, and adds the compositions of surfactant (sodium lauryl sulphate) wherein.Wherein,
1.CN101822673A leaching condition be paddle method, selection of speed 50rpm, dissolution medium is the water of 900mL, CN101822674A uses China's coastal port two annex XC dissolution methods second method (paddle method), with 900ml 0.1NHCl for dissolution medium, selection of speed 75rpm.Those skilled in the art knows, and increases the amount of dissolution medium, improves rotating speed and identical sample all can be made to improve dissolution.Random raising stripping rotating speed after increasing dissolution medium volume, dissolution results will not possess effective reference value, those skilled in the art knows the In vitro-in vivo correlation that such condition can not reach good.And under the condition provided at FDA, use the iloperidone sheet disclosed in patent CN101822673A and CN101822674A prepared by method can not reach the dissolution of more than 80% at 15min, the dissolution of more than 90% can not be reached during 30min.
2.CN101822673A requires to control the particle diameter of iloperidone below 30 μm, and CN101822674A requires to control particle diameter below 125 μm, and the particle diameter of preferred iloperidone is less than 90% be less than 75 μm.And CN101822673A demonstrates its product in 10min and the basic stripping completely of stripping 85%, 15min; The product that the embodiment 8 of CN101822674A demonstrates embodiment 1-6 at the dissolution of 30min all more than 90%.But described in 1 above, the leaching condition that these two patents adopt not is the iloperidone sheet leaching condition that FDA provides, and therefore dissolution results will not possess effective reference value.
3.CN101822673A with in the compositions of CN101822674A, sodium lauryl sulphate is adopted to be insoluble drug solubilising, improve its dissolution, but sodium lauryl sulphate has stimulation to mucosa and upper respiratory tract, there is stimulation to eye and skin, respiratory system anaphylactic reaction can be caused, by pyrolytic decomposition releasing poisonous gas, totally unfavorable to the safety of operator when this uses aborning in a large number, and be unfavorable for environmental protection.
Hydroxypropyl methylcellulose is classified as filler by 4.CN101822673A and CN101822674A, and those skilled in the art knows hydroxypropyl methylcellulose usually used as binding agent and slow release framework material.CN101822673A and CN101822674A thinks and can not use binding agent, and does not use the direct result of binding agent to be exactly loose particles for this kind of iloperidone, and mobility is deteriorated, and tablet weight variation becomes large, finally causes uniformity of dosage units defective.Moreover, the hydrophilic such as hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethyl cellulose, polyvidone are better, be conducive to the hydrophilic improving hydrophobic substance, improve its stripping, and iloperidone is exactly the very strong material of a hydrophobicity.
Visible only two pieces, about the patent CN101822673A of the quick release of iloperidone and CN101822674A, does not provide a kind of desirable iloperidone Pharmaceutical composition.
Summary of the invention
The present invention is directed to the deficiency of existing iloperidone rapid release Pharmaceutical composition, provide a kind of composition simple, stripping is rapid, the iloperidone composition and method of making the same that dissolution is high.Hinge structure, present invention, avoiding the use of surfactant.
The invention provides a kind of iloperidone compositions, containing iloperidone, diluent, binding agent, disintegrating agent and lubricant, wherein the particle diameter of iloperidone is less than 25 μm.
Wherein the particle diameter of the iloperidone of more than 90% weight percentage is less than 10 μm, and preferably the particle diameter of the iloperidone of more than 90% weight percentage is less than 5 μm.
The present invention also provides a kind of iloperidone compositions, is made up of the component of following weight percentage: the lubricant of the iloperidone of 0.5%-10%, the diluent of 65%-93%, the binding agent of 0.6%-8%, the disintegrating agent of 5%-15% and 0.4%-2%.
Wherein diluent is selected from lactose, microcrystalline Cellulose, mannitol, sorbitol, xylitol, starch and dextrin; Binding agent is selected from hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethyl cellulose, polyvidone, hydroxypropyl cellulose, methylcellulose and ethyl cellulose; Disintegrating agent is selected from polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose; Lubricant is selected from magnesium stearate, micropowder silica gel, stearic acid, Pulvis Talci and Polyethylene Glycol.Said composition can exist with the form of tablet, capsule, granule.
The present invention also provides a kind of method preparing described iloperidone compositions, it is characterized in that the iloperidone that described particle diameter is less than 25 μm is obtained by the method for high pressure homogenize.
The present invention also provides the method for the iloperidone compositions described in another kind of preparation, it is characterized in that iloperidone that described particle diameter is less than 25 μm is that the hot alcoholic solution of high concentration by using iloperidone is directly mixed into the method for granulating in adjuvant and obtains.Wherein said alcohol is selected from ethanol or isopropyl alcohol.
The present invention also provides the method for the iloperidone compositions described in another kind of preparation, it is characterized in that iloperidone that described particle diameter is less than 25 μm is that the alcoholic solution of low concentration by using iloperidone is sprayed to the method for granulating in adjuvant and obtains.Wherein said alcohol is selected from ethanol or isopropyl alcohol.
Prescription of the present invention consists of:
In the present invention, the particle diameter of iloperidone is less than 25 μm, and the iloperidone particle diameter of more than 90% weight percentage is less than 10 μm, and the iloperidone particle diameter being preferably more than 90% weight percentage is less than 5 μm.
The present inventor once attempted using Universalpulverizer the particle diameter of iloperidone to be crushed to 200 orders (particle diameter 75 μm) below, adopt wet granulation, obtained solid preparation especially tablet, dissolution (the paddle method 50rpm of 15min, 37 DEG C, with 500ml 0.1NHCl for dissolution medium) all the time could not all the time could not more than 90% more than the dissolution of 80%, 30min.After again attempt use ball mill pulverizer, the particle diameter of iloperidone can to 300 orders (48 μm)-500 orders (25 μm), and obtained solid preparation still can not reach and discharge completely.
When using high pressure homogenizer to be dropped to below 25 μm by the particle diameter of iloperidone, dissolution significantly improves, when the particle diameter more than 90% controlling iloperidone is less than 10 μm, dissolution (the paddle method 50rpm of 15min can be realized, 37 DEG C, with 500ml 0.1NHCl for dissolution medium) more than the dissolution of 80%, 30min more than 90%, preferably more than 90% be less than the condition of 5 μm under the repeatability of the stability that can ensure the quality of products and technique.
The adjuvant that disintegrating agent, filler etc. are conducive to stripping uses more, more easily reach the effect of rapid disintegrate, but production cost is higher more at most for adjuvant use amount, and all wishes to reduce production cost in production.The amount of producing Raw at preparation is determined, can only reduce the use amount of adjuvant, and when auxiliary material proportion is reduced to a certain degree, iloperidone microgranule just cannot reach homodisperse effect as far as possible, being reflected in stripping is exactly that batch interior difference is large, and dissolution is not high enough.
In the present invention, diluent can be selected from from lactose, microcrystalline Cellulose, mannitol, sorbitol, xylitol, starch and dextrin.Diluent can account for the 65%-93% of tablet gross mass.
Binding agent can be selected from hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethyl cellulose, polyvidone, hydroxypropyl cellulose, methylcellulose and ethyl cellulose.Binding agent can account for the 0.6%-8% of tablet gross mass.
Disintegrating agent can be selected from polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose, the disintegrate effect of polyvinylpolypyrrolidone and carboxymethyl starch sodium is better than cross-linking sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose, and the sample that polyvinylpolypyrrolidone is prepared not as using carboxymethyl starch sodium due to the reason product stability of wherein peroxide impurity, but polyvinylpolypyrrolidone has new generation product listing, peroxide greatly reduces, and product stability is not a problem.In tablets disintegrating agent add simultaneously with additional disintegrate effect than only Nei Jia or additional disintegrate effective.Disintegrating agent can account for the 5%-15% of tablet gross mass.
The present invention's lubricants/glidants used is micropowder silica gel, magnesium stearate, stearic acid, Pulvis Talci and Polyethylene Glycol, also can be used in combination.The 0.4%-2% of tablet gross mass can be accounted for.
In the present invention, the existence form of iloperidone compositions is tablet, capsule or granule.Preparation technology is wet granulation.According to describing above, when using the method for high pressure homogenization to control iloperidone particle diameter, process route as shown in Figure 1.
Due to iloperidone in water dissolubility very little, so its solution will be used to granulate will select organic solvent, organic solvent that can be medical with ethanol and isopropyl alcohol the most suitable.
When using High Shear Mixer Granulator, because solvent volatilization is slow, so only make the iloperidone solution of high concentration with a small amount of alcohol, again because the dissolubility of iloperidone in alcohol is not high yet, need heating just can meet the demands.
At this, we define iloperidone concentration in solution and to be greater than under room temperature (25 DEG C) iloperidone concentration in iloperidone saturated solution, are the iloperidone solution of high concentration; On the contrary, in solution, iloperidone concentration to be less than or equal under room temperature (25 DEG C) iloperidone concentration in iloperidone saturated solution, is the iloperidone solution of low concentration.
In this case, process route as shown in Figure 2.
If just dry while adding solution when granulating, and time drying efficiency is sufficiently high, just can the smaller iloperidone solution of configuration concentration, such iloperidone just can dissolve at normal temperatures, does not need special control temperature.Such as fluidized-bed spray granulation, in this case, process route as shown in Figure 3.
Accompanying drawing 1: the process route when using the method for high pressure homogenization to control iloperidone particle diameter.
Accompanying drawing 2: the process route when using High Shear Mixer Granulator.
Accompanying drawing 3: process route just dry while adding solution when granulating.
Detailed description of the invention
By following object lesson, can more specifically bright the present invention, but the present invention is not limited to following example.Wherein content (%) refers to percentage by weight.
Following comparative example 1-4 be conventionally in CN101822673A and CN101822674A to size controlling below 30 μm or 75 μm, the iloperidone compositions of preparation.
Comparative example 1 controls particle diameter less than 75 μm, does not use surfactant
Preparation technology:
I) iloperidone raw material pulverizing, crosses 200 mesh sieves (75 μm) for subsequent use;
Ii) take iloperidone, lactose, microcrystalline Cellulose, 6% polyvinylpolypyrrolidone by recipe quantity and the hydroxypropyl emthylcellulose powder that is not configured to solution adds in High Speed Stirring Machine, start stirring makes mix homogeneously;
Iii) add 2.5% hydroxypropyl emthylcellulose aqueous solution to granulate;
Iv) gained granule is used fluid bed drying;
V) other 5% polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate is added in granule, mix homogeneously;
Vi) tabletted.
Comparative example 2 controls particle diameter less than 30 μm, uses surfactant
Preparation technology:
I) iloperidone flow of feed gas be crushed to less than 30 μm for subsequent use;
Ii) take iloperidone, lactose, microcrystalline Cellulose, sodium lauryl sulphate, 6% polyvinylpolypyrrolidone by recipe quantity and the hydroxypropyl emthylcellulose powder that is not configured to solution adds in High Speed Stirring Machine, start stirring makes mix homogeneously;
Iii) add 2.5% hydroxypropyl emthylcellulose aqueous solution to granulate;
Iv) gained granule is used fluid bed drying;
V) another 5% polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate is added in granule, mix homogeneously;
Vi) tabletted.
Comparative example 3 controls particle diameter less than 75 μm, uses surfactant
Preparation technology:
I) iloperidone raw material pulverizing, crosses 200 mesh sieves (75 μm) for subsequent use;
Ii) take iloperidone, lactose, microcrystalline Cellulose, sodium lauryl sulphate, polyvinylpolypyrrolidone by recipe quantity and the hydroxypropyl emthylcellulose powder that is not configured to solution adds in High Speed Stirring Machine, start stirring makes mix homogeneously;
Iii) add 2.5% hydroxypropyl emthylcellulose aqueous solution to granulate;
Iv) gained granule is used fluid bed drying;
V) micropowder silica gel and magnesium stearate is added in granule, mix homogeneously;
Vi) granule is packed as.
The comparative example 4 formula preparation capsule of comparative example 3
In use comparative example 3, v) gained granule filling is suitable for the capsule of size.
Following embodiment 1-6 is the iloperidone compositions prepared according to technical scheme of the present invention.
Embodiment 1 high pressure homogenization method, controls more than 90% particle diameter and is less than 5 μm
Preparation technology:
I) iloperidone raw material pulverizing, crosses 100 mesh sieves (150 μm) for subsequent use;
Ii) iloperidone crossing 100 mesh sieves is scattered in 2.5% hydroxypropyl emthylcellulose aqueous solution the first suspension formed containing iloperidone 13%;
Iii) just the particle diameter more than 90% of suspension iloperidone in high pressure homogenize to suspension is less than 5 μm;
Iv) to measure after high pressure homogenize iloperidone content in suspension, calculate, and be diluted to 2.5% hydroxypropyl emthylcellulose aqueous solution the suspension that iloperidone content is 10%;
V) take lactose, microcrystalline Cellulose, 6% polyvinylpolypyrrolidone by recipe quantity and the hydroxypropyl emthylcellulose powder that is not configured to solution adds in High Speed Stirring Machine, start stirring makes mix homogeneously;
Vi) iv is added) middle suspension granulation;
Vii) gained granule is used fluid bed drying;
Viii) another 5% polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate is added in granule, mix homogeneously;
Ix) tabletted.
Embodiment 2 high pressure homogenization method, controls more than 90% particle diameter and is less than 10 μm
Preparation technology:
I) iloperidone raw material pulverizing, crosses 100 mesh sieves (150 μm) for subsequent use;
Ii) iloperidone crossing 100 mesh sieves is scattered in 2.5% hydroxypropyl emthylcellulose aqueous solution the first suspension formed containing iloperidone 13%;
Iii) just the particle diameter more than 90% of suspension iloperidone in high pressure homogenize to suspension is less than 10 μm;
Iv) to measure after high pressure homogenize iloperidone content in suspension, calculate, and be diluted to 2.5% hydroxypropyl emthylcellulose aqueous solution the suspension that iloperidone content is 10%;
V) take lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone by recipe quantity and the hydroxypropyl emthylcellulose powder that is not configured to solution adds in High Speed Stirring Machine, start stirring makes mix homogeneously;
Vi) iv is added) middle suspension granulation;
Vii) gained granule is used fluid bed drying;
Viii) micropowder silica gel and magnesium stearate is added in granule, mix homogeneously;
Ix) granule is packed as.
The embodiment 3 formula preparation capsule of embodiment 2
Using viii in embodiment 2) gained granule filling is suitable for the capsule of size.
Embodiment 4 high pressure homogenization method, controls more than 90% particle diameter and is less than 25 μm
Preparation technology:
I) iloperidone raw material pulverizing, crosses 100 mesh sieves (150 μm) for subsequent use;
Ii) iloperidone crossing 100 mesh sieves is scattered in 5% hydroxypropyl emthylcellulose aqueous solution the first suspension formed containing iloperidone 21%;
Iii) just the particle diameter more than 90% of suspension iloperidone in high pressure homogenize to suspension is less than 25 μm;
Iv) to measure after high pressure homogenize iloperidone content in suspension, calculate, and be diluted to 5% hydroxypropyl emthylcellulose aqueous solution the suspension that iloperidone content is 20%;
V) take lactose, microcrystalline Cellulose, 6% polyvinylpolypyrrolidone by recipe quantity and the hydroxypropyl emthylcellulose powder that is not configured to solution adds in High Speed Stirring Machine, start stirring makes mix homogeneously;
Vi) iv is added) middle suspension granulation;
Vii) gained granule is used fluid bed drying;
Viii) another 5% polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate is added in granule, mix homogeneously;
Ix) tabletted.
In following embodiment 5 and 6, be dissolved in alcohol by iloperidone and form solution, now iloperidone exists with molecularity, and physics's middle finger goes out the size of hydrone (molecular weight 18) 10
-10m (10
-4μm) on the order of magnitude, the molecular weight of iloperidone is 426.48, and mixed with adjuvant by this solution and granulate, the particle diameter that must meet iloperidone is less than 25 μm.
The hot alcoholic solution of embodiment 5 is granulated
Preparation technology:
I) iloperidone raw material is dissolved in dehydrated alcohol, forms the solution (temperature remains on more than 40 DEG C) of 5%;
Ii) taking lactose, microcrystalline Cellulose, 6% polyvinylpolypyrrolidone and hydroxypropyl emthylcellulose powder by recipe quantity adds in High Speed Stirring Machine, and start stirring makes mix homogeneously;
Iii) maintain the temperature at more than 40 DEG C, add iloperidone alcoholic solution and granulate;
Iv) gained granule is used fluid bed drying;
V) another 5% polyvinylpolypyrrolidone, micropowder silica gel and magnesium stearate is added in granule, mix homogeneously;
Vi) tabletted.
Embodiment 6 alcoholic solution is granulated
Preparation technology:
I) iloperidone raw material is dissolved in dehydrated alcohol, forms the solution of 0.5%;
Ii) use fluid bed top spray granulating process to be sprayed onto in lactose powder by iloperidone solution to granulate, and make iloperidone content reach prescription ratio;
Iii) microcrystalline Cellulose, polyvinylpolypyrrolidone and hydroxypropyl emthylcellulose powder and ii is taken by recipe quantity) middle gained granule mix homogeneously;
Iv) micropowder silica gel and magnesium stearate is added, mix homogeneously;
V) tabletted.
Embodiment 7 dissolution determination
According to the suggestion of FDA website, according to Chinese Pharmacopoeia version annex XC dissolution determination second method (paddle method in 2010, tablet) 50rpm and Chinese Pharmacopoeia version annex XC dissolution determination first method (paddle method in 2010, granule and capsule) 100rpm, with 500ml 0.1N HCl for dissolution medium, 37 DEG C, get a mensuration at 15min and 30min.Comparative example and embodiment result as follows:
As seen from the above table, utilize the technology of CN101822673A and CN101822674A, the iloperidone compositions of preparation, particle diameter is less than 30 μm or be less than 75 μm, no matter whether use surfactant, all fails to obtain gratifying In Vitro Dissolution result.And utilize the iloperidone compositions prepared by prescription of the present invention and technique, all obtain gratifying In Vitro Dissolution result.
Although above-described embodiment only lists do diluent with lactose and microcrystalline Cellulose, binding agent is done with hydroxypropyl emthylcellulose, disintegrating agent is done with polyvinylpolypyrrolidone, do the compositions of disintegrating agent with magnesium stearate and micropowder silica gel, but the present inventor demonstrates and wherein ought be selected from lactose, microcrystalline Cellulose, mannitol, sorbitol, xylitol, starch and dextrin by diluent by experiment; Binding agent is selected from hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethyl cellulose, polyvidone, hydroxypropyl cellulose, methylcellulose and ethyl cellulose; Disintegrating agent is selected from polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose; Lubricant be selected from magnesium stearate, micropowder silica gel, stearic acid, Pulvis Talci and Polyethylene Glycol time, also can realize effect of the present invention, in view of length relation, enumerate no longer one by one herein.
Claims (10)
1. an iloperidone compositions, containing iloperidone, diluent, binding agent, disintegrating agent and lubricant, it is characterized in that the particle diameter of iloperidone is less than 25 μm, the iloperidone that described particle diameter is less than 25 μm is obtained by the method for high pressure homogenize, or the hot alcoholic solution passing through the high concentration of use iloperidone is directly mixed into the method acquisition of granulating in adjuvant, or to be obtained by the method using the alcoholic solution of low concentration of iloperidone to be sprayed to granulate in adjuvant, its middle and high concentration to refer in solution that iloperidone concentration to be greater than at room temperature 25 DEG C iloperidone concentration in iloperidone saturated solution, low concentration to refer in solution that iloperidone concentration to be less than or equal at room temperature 25 DEG C iloperidone concentration in iloperidone saturated solution.
2. iloperidone compositions according to claim 1, is characterized in that the particle diameter of the iloperidone of more than 90% weight percentage is less than 10 μm.
3. iloperidone compositions according to claim 1, is characterized in that the particle diameter of the iloperidone of more than 90% weight percentage is less than 5 μm.
4. iloperidone compositions according to claim 1, is characterized in that being made up of the component of following weight percentage: the lubricant of the iloperidone of 0.5%-10%, the diluent of 65%-93%, the binding agent of 0.6%-8%, the disintegrating agent of 5%-15% and 0.4%-2%.
5. iloperidone compositions according to claim 4, is characterized in that diluent is selected from lactose, microcrystalline Cellulose, mannitol, sorbitol, xylitol, starch and dextrin.
6. iloperidone compositions according to claim 4, is characterized in that binding agent is selected from hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethyl cellulose, polyvidone, hydroxypropyl cellulose, methylcellulose and ethyl cellulose.
7. iloperidone compositions according to claim 4, is characterized in that disintegrating agent is selected from polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose.
8. iloperidone compositions according to claim 4, is characterized in that lubricant is selected from magnesium stearate, micropowder silica gel, stearic acid, Pulvis Talci and Polyethylene Glycol.
9. the iloperidone compositions according to any one of claim 1-8, is characterized in that existence form is tablet, capsule, granule.
10. iloperidone compositions according to claim 1, is characterized in that described alcohol is selected from ethanol or isopropyl alcohol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201110145252.XA CN102805745B (en) | 2011-06-01 | 2011-06-01 | Iloperidone composition and preparation method thereof |
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Non-Patent Citations (3)
| Title |
|---|
| 胡英 等.药物理化性质的影响.《生物药物制剂技术》.化学工业出版社,2010,第88页. * |
| 高压均质法制备阿奇霉素超微粉体;王龙艳 等;《化工时刊》;20050930;第19卷(第9期);第29-31页 * |
| 黄胜炎.国外新批准上市的药物新制剂新剂型(140).《中国制药信息》.2009,第25卷(第9期),第16页. * |
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