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 invention relates to a pharmaceutical composition for resisting schizophrenia, in particular to a pharmaceutical composition containing iloperidone and a preparation method thereof.
Background
Schizophrenia is a disease characterized by deep cognitive and emotional divisions that manifest as the most fundamental human behavior affected, such as language, thinking, perception and self-perception. The symptoms of the disease are included in a wide range, most commonly mental disorders such as hallucinations, delusions, and delusions.
Iloperidone not only reduces the occurrence of extrapyramidal syndrome (EPS) while effectively treating schizophrenia positive symptoms (hallucinations, delusions, disorganized thinking, enemies, suspicions, bizarre behavior), but also improves schizophrenia negative symptoms (blunted responses, emotional and language calmness, social withdrawal, and lack of attention).
The structure of iloperidone (iloperidone) was first disclosed by european patent EP402644 at 1990, 12 and 19. MoleculeFormula is C24H27FN2O4The structural formula is as follows:
chinese patent CN 1578664a (published on 9.2.2005) and its division CN101912367A (published on 15.12.2010) disclose a depot formulation of iloperidone and a polymer to achieve controlled release of iloperidone over 2-6 weeks for long-acting antipsychotics. CN101553211A (published 10/7/2009) discloses a controlled release formulation, wherein the drug is dispersed in a solubilizing polymer to form a solid dispersion, which provides effective blood levels for at least 18 hours; WO2004006886 (published 1/22 in 2004) discloses also an depot formulation of iloperidone. WO2010011232 (published on 28.1.2010) discloses an atypical antipsychotic drug comprising iloperidone in combination with succinic acid and fumaric acid to achieve controlled release of the drug.
The above patents disclose long acting controlled release formulations of iloperidone.
In 2009, 5 months, iloperidone tablets were approved by the Food and Drug Administration (FDA) for marketing and trade nameCan be used for acute treatment of adult schizophrenia with specification of 1mg, 2mg, 4mg, 6mg, 8mg, 10mg, and 12 mg. The adjuvants are lactose monohydrate, microcrystalline cellulose, hydroxypropyl methylcellulose, crospovidone, magnesium stearate, micropowder silica gel and purified water (evaporated during preparation), and are prepared by wet granulation and tabletting. According to clinical conditionsAccording to the research result, the dissolution rate of iloperidone in the product is required to exceed 80% at 15min and 90% at 30min, and the iloperidone needs to be rapidly released and reach blood concentration; cmax is reached 2-4 h after oral administration; relative growth compared to oral solutionThe bioavailability was 96%.
Iloperidone is a crystalline powder that is almost insoluble in water and has little solubility in 0.1N HCl. Therefore, in order to meet the requirement of rapid drug release, iloperidone must be prepared into a pharmaceutical preparation with good dissolution property.
As has been described above, in the above-mentioned,the specification discloses various auxiliary materials used by the prescription, and the wet granulation is inferred to be used, the inventor of the invention adopts the wet granulation to adjust the dosage of various auxiliary materials for a plurality of times according to the disclosed auxiliary materials, but the obtained iloperidone tablets can not be obtainedThe dissolution result disclosed in the specification is only about 60% after 30 min. (dissolution determination adopts the dissolution conditions of iloperidone tablets provided by FDA, paddle method 50rpm, 37 ℃, and 500ml of 0.1N HCl as dissolution medium.)
It is thus extremely difficult to obtain satisfactory iloperidone tablets even when the type of the various adjuvants is known unambiguously and the amount thereof is not known.
Chinese patents CN101822673A and CN101822674A (both published on 9/8 2010) disclose compositions in which iloperidone is micronized and a surfactant (sodium lauryl sulfate) is added thereto. Wherein,
the dissolution conditions of CN101822673A are paddle method, the rotation speed is 50rpm, the dissolution medium is 900mL of water, CN101822674A is the second dissolution method (paddle method) of XC dissolution method in appendix II of Chinese pharmacopoeia 2005 edition, 900mL of 0.1N Cl is used as dissolution medium, and the rotation speed is 75 rpm. It is well known to those skilled in the art that increasing the amount of dissolution medium and increasing the rotational speed all result in increased dissolution of the same sample. After the dissolution rotating speed is increased and the volume of the dissolution medium is increased freely, the dissolution result does not have effective reference value, and the person skilled in the art knows that the conditions can not achieve good in vivo and in vitro correlation. On the other hand, the iloperidone tablets prepared by the methods disclosed in patents CN101822673A and CN101822674A under the condition provided by FDA cannot reach the dissolution rate of 80% or more in 15min, and cannot reach the dissolution rate of 90% or more in 30 min.
CN101822673A requires that the particle size of iloperidone is controlled below 30 μm, CN101822674A requires that the particle size is controlled below 125 μm, and the particle size of iloperidone is preferably below 90% and below 75 μm. And CN101822673A proves that the product is dissolved out 85% in 10min and is basically and completely dissolved out in 15 min; CN101822674A, example 8, demonstrated that the products of examples 1-6 all had dissolution rates above 90% at 30 min. However, as described in 1 above, the dissolution conditions used in these two patents are not FDA-supplied dissolution conditions for iloperidone tablets, and thus the dissolution results would not be of significant reference value.
In the composition of CN101822673A and CN101822674A, sodium dodecyl sulfate is used as a poorly soluble drug to solubilize, so that the dissolution rate is improved, but the sodium dodecyl sulfate has a stimulating effect on mucous membranes and upper respiratory tracts, eyes and skin, can cause respiratory system allergic reaction, is decomposed by high heat to release toxic gas, and is extremely unfavorable for the safety of operators in production and not environment-friendly.
CN101822673A and CN101822674A classify hydroxypropylmethylcellulose as a filler, whereas hydroxypropylmethylcellulose is well known to those skilled in the art as a binder and a slow-release skeleton material in general. CN101822673A and CN101822674A suggest that no binder can be used, and the direct consequence of using no binder for iloperidone is loose particles, poor flowability, large piece weight difference, and finally unsatisfactory content uniformity. Moreover, hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethylcellulose, povidone and the like have good hydrophilicity, and are beneficial to improving the hydrophilicity of hydrophobic substances and improving the dissolution of the hydrophobic substances, and iloperidone is a substance with strong hydrophobicity.
It can be seen that the only two patents relating to the rapid release of iloperidone, CN101822673A and CN101822674A, do not provide an ideal pharmaceutical composition of iloperidone.
Disclosure of Invention
Aiming at the defects of the existing iloperidone quick-release medicinal composition, the invention provides an iloperidone composition with simple composition, quick dissolution and high dissolution rate and a preparation method thereof. Compared with the prior art, the invention avoids the use of a surfactant.
The invention provides an iloperidone composition which comprises iloperidone, a diluent, a binder, a disintegrant and a lubricant, wherein the particle size of the iloperidone is less than 25 mu m.
Wherein more than 90 percent of iloperidone by weight has a particle size of less than 10 μm, and preferably more than 90 percent of iloperidone by weight has a particle size of less than 5 μm.
The invention also provides an iloperidone composition which comprises the following components in percentage by weight: 0.5-10% of iloperidone, 65-93% of diluent, 0.6-8% of adhesive, 5-15% of disintegrant and 0.4-2% of lubricant.
Wherein the diluent is selected from lactose, microcrystalline cellulose, mannitol, sorbitol, xylitol, starch and dextrin; the binder is selected from hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethylcellulose, polyvidone, hydroxypropyl cellulose, methylcellulose and ethyl cellulose; the disintegrant is selected from crospovidone, sodium carboxymethyl starch, croscarmellose sodium and low substituted hydroxypropyl cellulose; the lubricant is selected from magnesium stearate, silica gel, stearic acid, pulvis Talci and polyethylene glycol. The composition can be in the form of tablet, capsule, or granule.
The invention also provides a method for preparing the iloperidone composition, which is characterized in that the iloperidone with the particle size of less than 25 μm is obtained by a high-pressure homogenization method.
The invention also provides another method for preparing the iloperidone composition, which is characterized in that iloperidone with the particle size of less than 25 mu m is obtained by a method of directly mixing a high-concentration hot alcohol solution of iloperidone into auxiliary materials for granulation. Wherein the alcohol is selected from ethanol or isopropanol.
The invention also provides another method for preparing the iloperidone composition, which is characterized in that iloperidone with the particle size of less than 25 mu m is obtained by a method of granulating by spraying a low-concentration alcohol solution of iloperidone into auxiliary materials. Wherein the alcohol is selected from ethanol or isopropanol.
The prescription of the invention comprises:
the particle size of iloperidone in the invention is less than 25 μm, the particle size of iloperidone with more than 90 weight percent is less than 10 μm, and the particle size of iloperidone with more than 90 weight percent is preferably less than 5 μm.
The inventor of the invention tries to crush iloperidone to a particle size of less than 200 meshes (particle size of 75 μm) by using a universal crusher and adopts wet granulation to prepare a solid preparation, particularly a tablet, wherein 15min dissolution rate (paddle method 50rpm, 37 ℃, 500ml of 0.1N Cl is used as a dissolution medium) cannot exceed 80% all the time, and 30min dissolution rate cannot exceed 90% all the time. Then, by using a ball mill pulverizer, the particle size of iloperidone can reach 300 meshes (48 μm) to 500 meshes (25 μm), and the prepared solid preparation can not achieve complete release.
When the particle size of iloperidone is reduced to below 25 mu m by using a high-pressure homogenizer, the dissolution rate is obviously improved, when the particle size of iloperidone is controlled to be more than 90% and less than 10 mu m, the dissolution rate of 15min (paddle method 50rpm, 37 ℃, 500ml of 0.1NHCl is used as a dissolution medium) is more than 80%, the dissolution rate of 30min is more than 90%, and the quality stability and the process reproducibility can be ensured under the condition that preferably more than 90% and less than 5 mu m.
The more the disintegrating agent, filler and other auxiliary materials which are advantageous for dissolution are used, the more the effect of rapid disintegration is easily achieved, but the more the amount of the auxiliary materials is used, the higher the production cost is, and the production cost is desired to be reduced in the production of the product. The amount of the raw materials in the preparation production is determined, the use amount of the auxiliary materials can only be reduced as much as possible, and when the proportion of the auxiliary materials is reduced to a certain degree, the iloperidone particles cannot achieve the effect of uniform dispersion, which reflects that the dissolution is large in difference in batches and not high enough in dissolution rate.
The diluent in the present invention may be selected from lactose, microcrystalline cellulose, mannitol, sorbitol, xylitol, starch and dextrin. The diluent may comprise 65% to 93% of the total mass of the tablet.
The binder is selected from hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethylcellulose, povidone, hydroxypropyl cellulose, methylcellulose and ethyl cellulose. The binder may comprise 0.6% to 8% of the total mass of the tablet.
The disintegrant can be selected from crospovidone, sodium carboxymethyl starch, croscarmellose sodium and low-substituted hydroxypropyl cellulose, the disintegration effect of the crospovidone and sodium carboxymethyl starch is superior to that of the croscarmellose sodium and the low-substituted hydroxypropyl cellulose, the product stability of the crospovidone is inferior to that of a sample prepared by using the sodium carboxymethyl starch due to peroxide impurities, but the crospovidone is already on the market in a new generation, the peroxide is greatly reduced, and the problem of the product stability is not solved. The disintegrating effect of the disintegrant added internally and externally in the tablet is better than that of the disintegrant added internally or externally only. The disintegrant may comprise 5% to 15% of the total mass of the tablet.
The lubricant/glidant used in the present invention is aerosil, magnesium stearate, stearic acid, talc and polyethylene glycol, and can also be mixed for use. Can account for 0.4-2% of the total mass of the tablet.
Iloperidone compositions of the present invention are present in the form of tablets, capsules or granules. The preparation process is wet granulation. In view of the foregoing, when a high pressure homogenization process is used to control the iloperidone particle size, the process is shown in figure 1.
Since iloperidone has very low solubility in water, an organic solvent is selected for granulation using its solution, and the organic solvents that can be used for medical purposes are most suitably ethanol and isopropanol.
When high-speed stirring granulation is used, because the solvent is slowly volatilized, a high-concentration iloperidone solution is prepared by using a small amount of alcohol, and because the solubility of iloperidone in alcohol is not high, the iloperidone can be heated to meet the requirement.
Here, we define that iloperidone concentration in the solution is greater than iloperidone concentration in a saturated solution of iloperidone at room temperature (25 ℃), as a high concentration iloperidone solution; in contrast, iloperidone in the solution at a concentration less than or equal to the iloperidone concentration in the saturated solution of iloperidone at room temperature (25 ℃) is a low concentration iloperidone solution.
In this case, the process route is shown in FIG. 2.
If the solution is added during granulation and is dried at the same time, and the drying efficiency is high enough, an iloperidone solution with a relatively small concentration can be prepared, so that iloperidone can be dissolved at normal temperature without special temperature control. For example, fluidized bed spray granulation, in which case the process scheme is as shown in figure 3.
FIG. 1: a process route when using a high pressure homogenization method to control the iloperidone particle size.
FIG. 2 is a drawing: route when using high speed stirring granulation.
FIG. 3: the process route of adding the solution while drying when granulating.
Detailed Description
The present invention will be described more specifically by the following specific examples, but the present invention is not limited to the following examples. Wherein the content (%) means a weight percentage.
The following comparative examples 1 to 4 are iloperidone compositions prepared according to the prior art CN101822673A and CN101822674A with particle size controlled to 30 μm or less than 75 μm.
Comparative example 1 particle size was controlled to 75 μm or less without using a surfactant
The preparation process comprises the following steps:
i) crushing iloperidone raw material, and sieving with a 200-mesh sieve (75 μm) for later use;
ii) weighing iloperidone, lactose, microcrystalline cellulose, 6% crospovidone and hydroxypropyl methyl cellulose powder which is not prepared into solution according to the prescription amount, adding the materials into a high-speed stirring granulator, and stirring the materials to uniformly mix the materials;
iii) adding 2.5% hydroxypropyl methylcellulose aqueous solution for granulating;
iv) drying the resulting granules using a fluidized bed;
v) adding the other 5% of crospovidone, aerosil and magnesium stearate into the granules, and uniformly mixing;
vi) compressing into tablets.
Comparative example 2A surfactant was used while controlling the particle size to 30 μm or less
The preparation process comprises the following steps:
i) airflow crushing iloperidone raw material to below 30 mu m for later use;
ii) weighing iloperidone, lactose, microcrystalline cellulose, sodium dodecyl sulfate, 6% crospovidone and hydroxypropyl methyl cellulose powder which is not prepared into solution according to the prescription amount, adding the materials into a high-speed stirring granulator, and stirring the materials to uniformly mix the materials;
iii) adding 2.5% hydroxypropyl methylcellulose aqueous solution for granulating;
iv) drying the resulting granules using a fluidized bed;
v) adding another 5% of crospovidone, aerosil and magnesium stearate into the granules, and uniformly mixing;
vi) compressing into tablets.
Comparative example 3A surfactant was used while controlling the particle size to 75 μm or less
The preparation process comprises the following steps:
i) crushing iloperidone raw material, and sieving with a 200-mesh sieve (75 μm) for later use;
ii) weighing iloperidone, lactose, microcrystalline cellulose, sodium dodecyl sulfate, crospovidone and hydroxypropyl methyl cellulose powder which is not prepared into solution according to the prescription amount, adding the materials into a high-speed stirring granulator, and stirring the materials to uniformly mix the materials;
iii) adding 2.5% hydroxypropyl methylcellulose aqueous solution for granulating;
iv) drying the resulting granules using a fluidized bed;
v) adding the micro-powder silica gel and the magnesium stearate into the granules, and uniformly mixing;
vi) subpackaging into granules.
Comparative example 4 capsules were prepared with the formulation of comparative example 3
The granules obtained in v) of comparative example 3 were filled into capsules of suitable size.
The following examples 1-6 are iloperidone compositions prepared according to the teachings of the present invention.
Example 1 high pressure homogenization method, particle size of 90% or more was controlled to be less than 5 μm
The preparation process comprises the following steps:
i) pulverizing iloperidone raw material, and sieving with 100 mesh sieve (150 μm);
ii) dispersing iloperidone sieved by a 100-mesh sieve in a 2.5% hydroxypropyl methylcellulose aqueous solution to form an initial suspension containing 13% iloperidone;
iii) homogenizing the primary suspension under high pressure until the particle size of iloperidone in the suspension is more than 90% and less than 5 μm;
iv) measuring the content of iloperidone in the suspension after high-pressure homogenization, calculating, and diluting the suspension with 2.5% hydroxypropyl methylcellulose aqueous solution to obtain a suspension with the iloperidone content of 10%;
v) weighing lactose, microcrystalline cellulose, 6% crospovidone and hydroxypropyl methyl cellulose powder which is not prepared into solution according to the prescription amount, adding the weighed materials into a high-speed stirring granulator, and stirring the materials to uniformly mix the materials;
vi) adding the suspension in iv) to granulate;
vii) drying the resulting granules using a fluidized bed;
viii) adding 5% of crospovidone, aerosil and magnesium stearate into the granules, and mixing uniformly;
ix) compression into tablets.
Example 2 high pressure homogenization method, particle size of 90% or more less than 10 μm
The preparation process comprises the following steps:
i) pulverizing iloperidone raw material, and sieving with 100 mesh sieve (150 μm);
ii) dispersing iloperidone sieved by a 100-mesh sieve in a 2.5% hydroxypropyl methylcellulose aqueous solution to form an initial suspension containing 13% iloperidone;
iii) homogenizing the primary suspension under high pressure until the particle size of iloperidone in the suspension is more than 90% and less than 10 μm;
iv) measuring the content of iloperidone in the suspension after high-pressure homogenization, calculating, and diluting the suspension with 2.5% hydroxypropyl methylcellulose aqueous solution to obtain a suspension with the iloperidone content of 10%;
v) weighing lactose, microcrystalline cellulose, crospovidone and hydroxypropyl methyl cellulose powder which is not prepared into solution according to the prescription amount, adding the weighed materials into a high-speed stirring granulator, and stirring the materials to uniformly mix the materials;
vi) adding the suspension in iv) to granulate;
vii) drying the resulting granules using a fluidized bed;
viii) adding the micro-powder silica gel and magnesium stearate into the granules, and uniformly mixing;
ix) subpackaging into granules.
Example 3 capsules were prepared with the formulation of example 2
The granules obtained in viii) of example 2 are used to fill capsules of suitable size.
Example 4 high pressure homogenization method, particle size of 90% or more less than 25 μm
The preparation process comprises the following steps:
i) pulverizing iloperidone raw material, and sieving with 100 mesh sieve (150 μm);
ii) iloperidone sieved with a 100 mesh sieve is dispersed in a 5% hydroxypropyl methylcellulose aqueous solution to form an initial suspension containing 21% iloperidone;
iii) homogenizing the primary suspension under high pressure until the particle size of iloperidone in the suspension is more than 90% and less than 25 μm;
iv) measuring the content of iloperidone in the suspension after high-pressure homogenization, calculating, and diluting the suspension with 5% hydroxypropyl methylcellulose aqueous solution until the content of iloperidone is 20%;
v) weighing lactose, microcrystalline cellulose, 6% crospovidone and hydroxypropyl methyl cellulose powder which is not prepared into solution according to the prescription amount, adding the weighed materials into a high-speed stirring granulator, and stirring the materials to uniformly mix the materials;
vi) adding the suspension in iv) to granulate;
vii) drying the resulting granules using a fluidized bed;
viii) adding 5% of crospovidone, aerosil and magnesium stearate into the granules, and mixing uniformly;
ix) compression into tablets.
In examples 5 and 6 below, iloperidone was dissolved in alcohol to form a solution, where iloperidone was present in a molecular state, and the size of the water molecules (molecular weight 18) was physically indicated to be 10-10m(10-4Mum), the molecular weight of iloperidone is 426.48, and the particle size of iloperidone can be less than 25 μm by mixing the solution with auxiliary materials for granulation.
EXAMPLE 5 Hot alcohol solution granulation
The preparation process comprises the following steps:
i) dissolving iloperidone raw material in absolute ethyl alcohol to form a 5% solution (the temperature is kept above 40 ℃);
ii) weighing lactose, microcrystalline cellulose, 6% crospovidone and hydroxypropyl methyl cellulose powder according to the formula amount, adding into a high-speed stirring granulator, and stirring to mix uniformly after starting up;
iii) keeping the temperature above 40 ℃, adding an iloperidone ethanol solution for granulation;
iv) drying the resulting granules using a fluidized bed;
v) adding another 5% of crospovidone, aerosil and magnesium stearate into the granules, and uniformly mixing;
vi) compressing into tablets.
EXAMPLE 6 alcohol solution granulation
The preparation process comprises the following steps:
i) dissolving iloperidone raw material in absolute ethyl alcohol to form 0.5% solution;
ii) spraying the iloperidone solution into the lactose powder for granulation by using a fluidized bed top spray granulation process, and enabling the iloperidone content to reach the formula ratio;
iii) weighing microcrystalline cellulose, crospovidone and hydroxypropyl methyl cellulose powder according to the prescription amount and uniformly mixing the microcrystalline cellulose, the crospovidone and the hydroxypropyl methyl cellulose powder with the granules obtained in the ii);
iv) adding the superfine silica powder and the magnesium stearate, and uniformly mixing;
v) compression into tablets.
EXAMPLE 7 dissolution determination
According to the recommendations of FDA website, the second method (paddle method, tablet) 50rpm and the first method (paddle method, granule and capsule) 100rpm are determined according to the first dissolution rate of the 2010 edition of Chinese pharmacopoeia, the first supplement XC, the second supplement XC, the first supplement XC, the second supplement. The results of the comparative examples and examples are as follows:
as can be seen from the above table, iloperidone compositions prepared using the techniques of CN101822673A and CN101822674A, having particle sizes of less than 30 μm or less than 75 μm, failed to achieve satisfactory in vitro dissolution results regardless of the use of surfactants. The iloperidone composition prepared by the prescription and the process of the invention has satisfactory in-vitro dissolution results.
Although the above examples only exemplify compositions in which lactose and microcrystalline cellulose are used as diluents, hydroxypropylmethyl cellulose is used as a binder, crospovidone is used as a disintegrant, and magnesium stearate and aerosil are used as disintegrants, the inventors of the present invention have experimentally verified that when the diluents are selected from lactose, microcrystalline cellulose, mannitol, sorbitol, xylitol, starch, and dextrin; the binder is selected from hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethylcellulose, polyvidone, hydroxypropyl cellulose, methylcellulose and ethyl cellulose; the disintegrant is selected from crospovidone, sodium carboxymethyl starch, croscarmellose sodium and low substituted hydroxypropyl cellulose; the lubricant is selected from magnesium stearate, silica gel, stearic acid, talc and polyethylene glycol, and the effects of the present invention can be achieved, and are not shown in detail.
Claims (10)
1. Iloperidone composition contains iloperidone, a diluent, a binder, a disintegrant and a lubricant, and is characterized in that the particle size of iloperidone is less than 25 microns, the iloperidone with the particle size of less than 25 microns is obtained by a high-pressure homogenization method, or is obtained by a method of directly mixing a high-concentration hot alcohol solution of iloperidone into an auxiliary material for granulation, or is obtained by a method of spraying a low-concentration alcohol solution of iloperidone into the auxiliary material for granulation, wherein the high concentration refers to the concentration of iloperidone in the solution which is greater than that in an iloperidone saturated solution at 25 ℃ and the low concentration refers to the concentration of iloperidone in the solution which is less than or equal to that in the iloperidone saturated solution at 25 ℃.
2. Iloperidone composition of claim 1, characterized in that more than 90% by weight of iloperidone has a particle size of less than 10 μm.
3. Iloperidone composition of claim 1, characterized in that more than 90% by weight of iloperidone has a particle size of less than 5 μm.
4. Iloperidone composition according to claim 1, characterized by consisting of the following components in weight percent: 0.5-10% of iloperidone, 65-93% of diluent, 0.6-8% of adhesive, 5-15% of disintegrant and 0.4-2% of lubricant.
5. Iloperidone composition of claim 4, characterized in that the diluent is selected from lactose, microcrystalline cellulose, mannitol, sorbitol, xylitol, starch, and dextrin.
6. Iloperidone composition of claim 4, characterized in that the binder is selected from hydroxypropyl methylcellulose, polyoxyethylene, sodium carboxymethylcellulose, povidone, hydroxypropyl cellulose, methylcellulose, and ethylcellulose.
7. Iloperidone composition of claim 4, characterized in that the disintegrant is selected from crospovidone, sodium carboxymethyl starch, croscarmellose sodium, and low substituted hydroxypropyl cellulose.
8. Iloperidone composition of claim 4, characterized in that the lubricant is selected from magnesium stearate, aerosil, stearic acid, talc and polyethylene glycol.
9. Iloperidone composition according to any one of claims 1-8 characterized by being present in the form of tablets, capsules, granules.
10. Iloperidone composition of claim 1, characterized in that the alcohol is selected from ethanol or isopropanol.
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Non-Patent Citations (3)
| Title |
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| 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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