CN102327266A - Pharmaceutical composition containing Iloperidone and preparation method thereof - Google Patents
Pharmaceutical composition containing Iloperidone and preparation method thereof Download PDFInfo
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- CN102327266A CN102327266A CN 201110213386 CN201110213386A CN102327266A CN 102327266 A CN102327266 A CN 102327266A CN 201110213386 CN201110213386 CN 201110213386 CN 201110213386 A CN201110213386 A CN 201110213386A CN 102327266 A CN102327266 A CN 102327266A
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- iloperidone
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition containing Iloperidone and a preparation method thereof. In the invention, Iloperidone and lactose are prepared into solid dispersion, and a hydrophilic gel material is added to the prescription at the same time, thus improving the water insolubility of Iloperidone. The pharmaceutical composition containing Iloperidone provided by the invention has the characteristics that the water insolubility of Iloperidone is improved, the in-vitro dissolution is different from the characteristic that the traditional common preparation rapidly releases at the early stage, and the in-vitro dissolution is mild at the early stage, but is completed within 30 minutes.
Description
Technical field
The present invention relates to the schizoid pharmaceutical composition of a kind of treatment, particularly comprise stripping excellent drug composition and method of making the same as the iloperidone of active component.
Background technology
Iloperidone is the antagonist of 5-hydroxy tryptamine, d2 dopamine receptor, is mainly used in the treatment of the affective disorder that comprises ambipolar affective disorder.
The clinical consumption of announcing in the iloperidone description that FDA announces is 1mg, 2mg, 4mg, 6mg, 8mg, 10mg, 12mg.
United States Patent(USP) No. 5364866 discloses the chemical compound iloperidone and can be used as psychosis and analgesics.United States Patent(USP) No. 5955459 discloses the conjugate that contains fatty acid and iloperidone, has been used to treat schizoid compositions.
CN94194302.X and CN02821426.9 disclose the depot formulation of iloperidone and star-shape polymer, are used for long-acting psychosis.This preparation process thereof is complicated and need drug administration by injection, and patient's compliance is relatively poor.
Iloperidone is developed to oral solid formulation and can makes things convenient for the patient to take, and increase compliance, and technology is simple, is fit to domestic actual production equipment situation.
The dissolubility of report iloperidone is relatively poor in the FDA description, is poorly water soluble drugs, so be developed to oral solid formulation, the significant concern project that rises to of dissolution.Can reduce particle diameter through common grinding mode, when still hydrophobic iloperidone was pulverized separately, along with the increase of surface area, free energy increased, the easy phenomenon that reassembles of particle, and stripping is still incomplete.In addition, in the conventional formulation formulation and technology mentality of designing, tend to disintegration rate through improving preparation to improve dissolution, though rapid according to the Iloperidone drug composition disintegrate in early stage of this kind thinking preparation, final stripping is still incomplete.
Summary of the invention
For overcoming the difficult problem of iloperidone stripping, the present invention pulverizes iloperidone and lactose altogether and processes solid dispersion, has increased its hydrophilic, has improved the dissolution rate of small dimension iloperidone sheet greatly.Simultaneously; The change tradition formulation and technology mentality of designing of novelty of the present invention; The mentality of designing of slow releasing preparation is applied to ordinary preparation, changes the stripping behavior of preparation, slow down the preparation disintegration rate in early stage; Make slowly corrosion in its early stage, but obviously improved the dissolution of the Iloperidone drug composition of all clinical use specifications.
It is complete that the present invention has obtained stripping, and preparation technology is simple, is fit to the Iloperidone drug composition of industrialized great production.
Pharmaceutical composition provided by the present invention comprises iloperidone or its officinal salt, and pharmaceutically acceptable carrier.
On the one hand, its described iloperidone of pharmaceutical composition provided by the present invention has been prepared to solid dispersion.
Solid dispersion provided by the present invention, be with iloperidone with after lactose mixes, adopt polishing to be prepared from.
Solid dispersion provided by the present invention adopts jet mill to be prepared from.
Solid dispersion provided by the present invention, the consumption of its described lactose are 5～20 times iloperidone consumption (W/W), are preferable over 5～15 times iloperidone consumption (W/W), more preferably in 7～10 times iloperidone consumption (W/W).
Solid dispersion provided by the present invention, the particle diameter of its described iloperidone is less than 80 μ m.
Solid dispersion provided by the present invention has reduced the particle diameter of iloperidone on the one hand, has strengthened the hydrophilic of iloperidone particle surface on the other hand, this solid dispersion is prepared into the small dimension preparation after dissolution obviously improve.
On the other hand, pharmaceutical composition provided by the present invention, its described available pharmaceutical carrier comprises filler, hydrophilic gel material, disintegrating agent, lubricant.
Pharmaceutical composition provided by the present invention, its described each component by following weight fraction than forming:
Pharmaceutical composition provided by the present invention, its described hydrophilic gel material are one or more in hypromellose, sodium carboxymethyl cellulose, the hydroxypropyl cellulose.
Pharmaceutical composition provided by the present invention, its described filler are one or more in lactose, microcrystalline Cellulose, starch, the calcium hydrogen phosphate.
Pharmaceutical composition provided by the present invention, its described disintegrating agent are one or more in carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl methylcellulose, the polyvinylpolypyrrolidone.
Pharmaceutical composition provided by the present invention, its described lubricant are one or more in magnesium stearate, the micropowder silica gel.
The present invention introduces ordinary preparation with the prescription mentality of designing of slow releasing preparation; The hydrophilic gel material that will have certain slow releasing function of novelty joins in the prescription; The stripping behavior of pharmaceutical composition provided by the present invention is different from the ordinary preparation of other rapid disintegrates; The slow corrosion of stripping preparation in early stage, but it is complete finally to understand stripping, adopts this method to improve the dissolution of high standard Iloperidone drug composition.
In sum, this bright preparation of drug combination method that provides comprises:
(1) with iloperidone and a certain amount of lactose mix homogeneously, adopt jet mill to pulverize jointly, process solid dispersion;
(2) with the filler of above-mentioned solid dispersion and recipe quantity, hydrophilic gel material, in add part disintegrating agent mix homogeneously, add purified water, the system soft material; Granulate with 18 mesh sieves, in 50 ℃ of temperature aeration-dryings, with 24 mesh sieve granulate; Weighing; The disintegrating agent and the lubricant that add Extra Section in proportion, mix homogeneously, tabletting.
The pharmaceutical composition that contains iloperidone provided by the present invention, all clinical use specification preparations are all leachable fully, and preparation technology is simple, are fit to domestic production equipment situation, are prone to realize industrialization.
The specific embodiment
Come medical composition of the present invention done further specifying through following examples, but be not limited in following instance.
Embodiment 1:
Method for preparing:
(1) with the lactose mix homogeneously of iloperidone and recipe quantity, adopt jet mill to pulverize jointly, process solid dispersion;
(2) with the lactose of above-mentioned solid dispersion and filler recipe quantity, hypromellose, in add the low-substituted hydroxypropyl cellulose mix homogeneously of part, add purified water, the system soft material; Granulate with 18 mesh sieves; In 50 ℃ of temperature aeration-dryings, with 24 mesh sieve granulate, weighing; The low-substituted hydroxypropyl cellulose, magnesium stearate and the micropowder silica gel mix homogeneously that add Extra Section in proportion, tabletting.
Embodiment 2:
Method for preparing:
(1) with the lactose mix homogeneously of iloperidone and recipe quantity, adopt jet mill to pulverize jointly, process solid dispersion;
(2) with the lactose of above-mentioned solid dispersion and filler recipe quantity, microcrystalline Cellulose, hydroxypropyl cellulose, in add the part of sodium carboxymethyl starch mix homogeneously, add purified water, the system soft material; Granulate with 18 mesh sieves, in 50 ℃ of temperature aeration-dryings, with 24 mesh sieve granulate; Weighing; The carboxymethyl starch sodium and the magnesium stearate that add Extra Section in proportion, mix homogeneously, tabletting.
Embodiment 3:
Method for preparing:
(1) with the lactose mix homogeneously of iloperidone and recipe quantity, adopt jet mill to pulverize jointly, process solid dispersion;
(2) with the calcium hydrogen phosphate of above-mentioned solid dispersion and recipe quantity, sodium carboxymethyl cellulose, in add partial cross-linked sodium carboxymethyl cellulose mix homogeneously, add purified water, the system soft material; Granulate with 18 mesh sieves, in 50 ℃ of temperature aeration-dryings, with 24 mesh sieve granulate; Weighing; The cross-linking sodium carboxymethyl cellulose, magnesium stearate and the micropowder silica gel that add Extra Section in proportion, mix homogeneously, tabletting.
Embodiment 4:
Method for preparing:
(1) with the lactose mix homogeneously of iloperidone and recipe quantity, adopt jet mill to pulverize jointly, process solid dispersion;
(2) with the lactose of above-mentioned solid dispersion and filler recipe quantity, hypromellose, in add part disintegrating agent polyvinylpolypyrrolidone mix homogeneously, add purified water, the system soft material; Granulate with 18 mesh sieves, in 50 ℃ of temperature aeration-dryings, with 24 mesh sieve granulate; Weighing; The polyvinylpolypyrrolidone and the magnesium stearate that add Extra Section in proportion, mix homogeneously, tabletting.
The comparative example 1:
Method for preparing:
(1) adopt jet mill to pulverize separately iloperidone;
(2) with the lactose of above-mentioned solid dispersion and recipe quantity, hypromellose, in add partial cross-linked polyvidone mix homogeneously, add purified water, the system soft material; Granulate with 18 mesh sieves, in 50 ℃ of temperature aeration-dryings, with 24 mesh sieve granulate; Weighing; The polyvinylpolypyrrolidone and the magnesium stearate that add Extra Section in proportion, mix homogeneously, tabletting.
The comparative example 2:
Method for preparing:
(1) with the lactose mix homogeneously of iloperidone and recipe quantity, adopt jet mill to pulverize jointly, process solid dispersion;
(2) with the lactose of above-mentioned solid dispersion and filler recipe quantity, in add partial cross-linked polyvidone mix homogeneously, add purified water, the system soft material; Granulate with 18 mesh sieves, in 50 ℃ of temperature aeration-dryings, with 24 mesh sieve granulate; Weighing; The polyvinylpolypyrrolidone and the magnesium stearate that add Extra Section in proportion, mix homogeneously, tabletting.
Measure prepared Iloperidone drug composition among the embodiment of the invention 4, comparative example 1 and the comparative example 2 according to dissolution determination method (two appendix of Chinese Pharmacopoeia version in 2010); With 500ml water is medium; Rotating speed is that per minute 50 changes; Respectively at 5,10,15,30,45,60 minutes sampling test sample dissolutions, the result was following:
Table 1. embodiment 4, comparative example 1, the comparative example 2 dissolution % (n=6) in aqueous medium
Description of drawings
Fig. 1. embodiment 4, comparative example 1, the comparative example 2 dissolution curve contrast in water
Can know that by table 1 and Fig. 1 comparative example 1 is not prepared into solid dispersion, comparative example 2 with iloperidone and does not add hydrophilic gel material and cause eventually can't stripping complete; And embodiment 4 has changed its stripping behavior because iloperidone has been prepared into solid dispersion with lactose and in prescription, has added hydrophilic gel material, and early stage, the time point stripping was slow, but final leachable complete.
It is thus clear that Iloperidone drug composition provided by the invention can change the slightly water-soluble of iloperidone itself, make slowly corrosion in its early stage, 30 minutes can be in aqueous medium stripping complete, improved the dissolution of Iloperidone drug composition conscientiously.
Claims (12)
1. pharmaceutical composition that contains iloperidone is characterized in that comprising the solid dispersion, the hydrophilic gel material with hydrotropy effect and the pharmaceutically acceptable carrier that contain the iloperidone that hydrophilic improves.
2. pharmaceutical composition according to claim 1 is characterized in that described solid dispersion is prepared from iloperidone and lactose mixed grinding.
3. pharmaceutical composition according to claim 2 is characterized in that lactose consumption in the described solid dispersion is 5～20 times an iloperidone consumption (W/W).
4. pharmaceutical composition according to claim 2 is characterized in that lactose consumption in the described solid dispersion is 5～15 times an iloperidone consumption (W/W).
5. pharmaceutical composition according to claim 2 is characterized in that lactose consumption in the described solid dispersion is 7～10 times an iloperidone consumption (W/W).
6. pharmaceutical composition according to claim 1 is characterized in that 2%～8% (w/w) of described hydrophilic gel material for prescription.
7. pharmaceutical composition according to claim 1 is characterized in that described hydrophilic gel material is one or more in hypromellose, sodium carboxymethyl cellulose, the hydroxypropyl cellulose.
8. pharmaceutical composition according to claim 1 is characterized in that said compositions is made up of following combination and weight fraction:
9. pharmaceutical composition according to claim 8 is characterized in that described filler is one or more in lactose, microcrystalline Cellulose, starch, the calcium hydrogen phosphate.
10. pharmaceutical composition according to claim 8 is characterized in that described disintegrating agent is one or more in carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl methylcellulose, the polyvinylpolypyrrolidone.
11. pharmaceutical composition according to claim 8 is characterized in that described lubricant is one or more in magnesium stearate, the micropowder silica gel.
12. the preparation of drug combination method according to claim 1-11 comprises:
(1), adopt jet mill to pulverize jointly with iloperidone and a certain amount of lactose mix homogeneously;
(2) with the filler of above-mentioned solid dispersion and recipe quantity, hydrophilic gel material, in add part disintegrating agent mix homogeneously, add purified water, the system soft material; Granulate with 18 mesh sieves, in 50 ℃ of temperature aeration-dryings, with 24 mesh sieve granulate; Weighing; The disintegrating agent and the lubricant that add Extra Section in proportion, mix homogeneously, tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110213386 CN102327266A (en) | 2011-07-28 | 2011-07-28 | Pharmaceutical composition containing Iloperidone and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110213386 CN102327266A (en) | 2011-07-28 | 2011-07-28 | Pharmaceutical composition containing Iloperidone and preparation method thereof |
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| CN102327266A true CN102327266A (en) | 2012-01-25 |
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| CN 201110213386 Pending CN102327266A (en) | 2011-07-28 | 2011-07-28 | Pharmaceutical composition containing Iloperidone and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670532A (en) * | 2012-05-21 | 2012-09-19 | 上海医药工业研究院 | Iloperidone medicine composition and preparation method thereof |
| CN103239407A (en) * | 2012-02-08 | 2013-08-14 | 中国医药研究开发中心有限公司 | Solid composition containing iloperidone medicament and preparation method thereof |
| CN105796516A (en) * | 2016-03-21 | 2016-07-27 | 山东省药学科学院 | Method for preparing iloperidone tablets |
| 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 |
-
2011
- 2011-07-28 CN CN 201110213386 patent/CN102327266A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103239407A (en) * | 2012-02-08 | 2013-08-14 | 中国医药研究开发中心有限公司 | Solid composition containing iloperidone medicament and preparation method thereof |
| CN102670532A (en) * | 2012-05-21 | 2012-09-19 | 上海医药工业研究院 | Iloperidone medicine composition and preparation method thereof |
| 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 |
| CN105796516A (en) * | 2016-03-21 | 2016-07-27 | 山东省药学科学院 | Method for preparing iloperidone tablets |
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Application publication date: 20120125 |