CN102600132A - Oral preparation containing amisulpride - Google Patents
Oral preparation containing amisulpride Download PDFInfo
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- CN102600132A CN102600132A CN2012100651709A CN201210065170A CN102600132A CN 102600132 A CN102600132 A CN 102600132A CN 2012100651709 A CN2012100651709 A CN 2012100651709A CN 201210065170 A CN201210065170 A CN 201210065170A CN 102600132 A CN102600132 A CN 102600132A
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Abstract
The invention relates to an oral preparation containing amisulpride. The amisulpride which is active medicine is prepared into cyclodextrin inclusion compound, is sieved, is uniformly mixed with pharmaceutically acceptable auxiliary materials, and is granulated by a wet method or a dry method, obtained granules are squashed to form tablets, filled into capsules to form a capsule preparation or is directly separately packaged to obtain a granule preparation. The water solubility and the stability of the oral preparation containing the amisulpride can be strengthened, bitter taste of the amisulpride is covered, medication compliances of patients are improved, and bioavailability of the oral preparation is improved to a great extent.
Description
Technical field
The present invention relates to a kind of oral formulations that contains amisulpride, belong to the pharmaceutical preparations technology field.
Background technology
Amisulpride is an atypical antipsychotic used to conduct classes paranoid schizophrenia, acute treatment of psychosis jump Rui, can also be used to treat schizophrenia defect state, as well as with the evolution of residual psychotic There are dull suppressed.Amisulpride is that 100,200 and 400 milligrams tablet form orally uses (Vidal, edition2003, Solianmonograph, the 1736th and 1738 page) with every tablet amounts usually.Yet during acute psychotic episode, oral every day of the dosage of amisulpride often improves, and can reach 1200 mg/day.Therefore, use the patient of amisulpride treatment must swallow several pieces tablets every day.
Because the special pathological state of patient, and active component amisulpride taste is very bitter, and correct is abideed by doctor's advice and regularly taken a large amount of tablets and can meet difficulty, and perhaps even show significant being reticent, influences patient's compliance; Therefore press for the sensory issues that solves the amisulpride oral formulations.
Amisulpride is slightly soluble in water, but the quick stripping of clinical requirement medicine, onset rapidly, this just requires to adopt in the preparation production suitable prescription and technology to improve drug dissolution.
CN1842331A discloses a kind of amisulpride solid composite medicament, comprises by the amisulpride granule that coating coated and at least a mouthful interior pharmaceutically acceptable excipient of administration that disperses that is suitable for of lipid coating and polymer coating to form.The amisulpride pharmaceutical composition of the method preparation is that the granule that contains amisulpride is wrapped up, and specification is very big, and it is very big that it is made mouthful interior dispersible tablet difficulty, is difficult to reach the effect of quick stripping, rapid onset.
Summary of the invention
To the deficiency of prior art, the present invention provides the quick stripping of a kind of ability, onset rapidly, can cover the amisulpride oral formulations of its bitterness again.The present invention also provides a kind of method for preparing of said amisulpride oral formulations.
The term explanation:
Related substance: impurity generally is divided into organic impurities, inorganic impurity and residual solvent according to physicochemical property.Organic impurities comprises the impurity introduced in the technology and catabolite etc., possibly be known or unknown, volatile or fixedness; Because the chemical constitution of this type impurity is general and active component is similar or tool origin relation, so can be described as related substance usually again.
Technical scheme of the present invention is following:
A kind of amisulpride oral formulations contains the cyclodextrin and the pharmaceutically acceptable excipient of active drug amisulpride, enclose active drug; Wherein, amisulpride exists with the cyclodextrin clathrate form, and the mass ratio of amisulpride and cyclodextrin is 1: (0.5～4).
According to the present invention, preferred, the mass ratio of said amisulpride and cyclodextrin is 1: (1～3.5).The mass ratio of further preferred amisulpride and cyclodextrin is 1: (2～3.5)
According to the present invention, said cyclodextrin is selected from one or more in alpha-cyclodextrin, beta-schardinger dextrin-, the gamma-cyclodextrin; Preferred alpha-cyclodextrin, beta-schardinger dextrin-; Beta-schardinger dextrin-most preferably.
According to the present invention, preferred said excipient comprises diluent, disintegrating agent, binding agent and/or lubricant.
According to the present invention, preferably scheme is, a kind of amisulpride oral formulations is processed by the composition of following mass ratio:
Amisulpride 10%-50%, diluent 10%-50%, disintegrating agent 1%-10%, binding agent 0.5%-5%, lubricant 1%-5%, each composition sum is 100%; The amount that adds cyclodextrin is that the mass ratio of amisulpride and cyclodextrin is 1: (0.5～4).Wherein, the mass ratio of preferred amisulpride and cyclodextrin is 1: (1～3.5).The mass ratio of further preferred amisulpride and cyclodextrin is 1: (2～3.5)
According to the present invention, said diluent is preferably 15%-45%, and disintegrating agent is preferably 3.0-5.0%, and binding agent is preferably 0.5-3.0%, and lubricant is preferably 1.5-5.0%.
According to the present invention, adjuvants such as said diluent, disintegrating agent, binding agent, lubricant get final product by state of the art.The present invention is preferably following:
Said diluent is selected from one or more in microcrystalline Cellulose, lactose, mannitol, the pregelatinized Starch.
Said disintegrating agent is selected from one or more in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, carboxymethyl starch sodium and the low-substituted hydroxypropyl cellulose.
Said binding agent is selected from the mixture of synthetic copolymer or natural gum or synthetic copolymer and natural gum; Described synthetic copolymer is copolyvidone, hydroxypropyl cellulose, polyvinylpyrrolidone, hydroxypropyl emthylcellulose; Said natural gum is Radix Acaciae senegalis or xanthan gum.Preferably, binding agent is made into aqueous solution or hydrous ethanol solution adding.
Said lubricant is selected from one or more in magnesium stearate, Pulvis Talci, the silicon dioxide.
Preferred version one according to the present invention, said amisulpride oral formulations, and prescription is formed as follows:
Amisulpride 100g,
Beta-schardinger dextrin-350g,
Microcrystalline Cellulose 63g,
Polyvinylpolypyrrolidone 18g,
Polyvinylpyrrolidone 16g is mixed with 10wt% polyvinylpyrrolidone aqueous solution and adds,
Magnesium stearate 6g,
Silicon dioxide 3g,
Process 1000 units altogether.
Preferred version two according to the present invention, said amisulpride oral formulations, and prescription is formed as follows:
Amisulpride 100g,
Gamma-cyclodextrin 250g,
Lactose 137g,
Microcrystalline Cellulose 80g,
Carboxymethyl starch is received 24g,
Xanthan gum 3g is mixed with the 2wt% xanthan gum solution and adds,
Magnesium stearate 9g,
Process 1000 units altogether.
Preferred version three according to the present invention, said amisulpride oral formulations, and prescription is formed as follows:
Amisulpride 100g,
Alpha-cyclodextrin 200g,
Pregelatinized Starch 240g,
Carboxymethyl starch is received 30g,
Hydroxypropyl cellulose 5g is made into the solution that contains the 5wt% hydroxypropyl cellulose with the ethanol of concentration 75wt% and adds,
Pulvis Talci 30g,
Process 1000 units altogether.
But above-mentioned raw materials of the present invention all market is bought.
In order further to improve the dissolution of active component in the preparation, the present invention provides a kind of method for preparing of above-mentioned amisulpride oral formulations, comprises the steps:
(1) cyclodextrin of recipe quantity is processed 50-60 ℃ of saturated aqueous solution, in blender, stir then, rotating speed is 750 rev/mins-1500 rev/mins; The amisulpride of recipe quantity is dissolved in an amount of ethanol; Be added drop-wise to then in the cyclodextrin saturated aqueous solution that stirs; The control rate of addition is 1-3ml/ minute, maintains the temperature at 50-60 ℃, rotating speed after being added dropwise to complete and continues for 750 rev/mins-1500 rev/mins to stir 4 hours, stops to stir; Spray drying makes the amisulpride cyclodextrin clathrate; Perhaps,
The cyclodextrin of recipe quantity is added suitable quantity of water be developed into pasty state, pour in the colloid mill, grind; The amisulpride of recipe quantity is dissolved in an amount of ethanol, is added drop-wise to then in the ground pasty state cyclodextrin, the control rate of addition is 2-4ml/ minute, continues to grind 30-45 minute, and spray drying makes cyclodextrin clathrate;
(2) the amisulpride cyclodextrin clathrate that makes is crossed 100 mesh sieves; Add diluent, disintegrating agent, binding agent system soft material then, cross the 12-28 mesh sieve and make wet granular, with wet granular in 50-70 ℃ of intensive drying; Cross 10-24 mesh sieve granulate and must do granule, add lubricant and always mix.
(3) will always mix the gained granule and carry out that tabletting gets tablet, filled capsules gets capsule or direct packaging gets granule.
Preferably, the binding agent described in the above-mentioned steps (2) is made into aqueous solution or hydrous ethanol solution adding.In the above-mentioned method for preparing special limit all by state of the art.
The present invention is surprised to find that with cyclodextrin the principal agent amisulpride is wrapped up; Produced beat all excellent results; Amisulpride exists with the cyclodextrin clathrate form can either make medicine stripping fast, onset rapidly, can cover its bitterness again, is beneficial to patient's medication.
The inventor is surprised to find that, adopts the cyclodextrin inclusion compound amisulpride to prepare oral formulations, not to the utmost principal agent has been played the coating effect, has also improved the stability of oral formulations.Compare with the amisulpride oral formulations for preparing according to common process, have following excellent results:
1, can be good at covering the bitterness of amisulpride, increased insane medication compliance;
2, the related substance in the preparation significantly reduces, and has improved medicine stability;
3, can significantly improve the water solublity of principal agent, help medicine stripping fast in gastrointestinal tract, improve bioavailability;
4, preparation technology is simple, is fit to large-scale industrial production.
The specific embodiment
Below in conjunction with embodiment the present invention is further specified.It will be appreciated that; For those skilled in the art; In an embodiment of the present invention, clearly and can be easy to make and do not deviate from other embodiment and the modification of the scope and the aim of the invention described above, all be included in protection scope of the present invention.Therefore, the scope that should not be construed as claims is limited in following examples.
For the ease of contrast, the formula ratio in following examples and the Comparative Examples is the amount of 1000 preparation units, and promptly tablet is 1000, and capsule is 1000, and granule is 1000 bags.
Embodiment 1: amisulpride oral formulations prescription:
Supplementary material title consumption
Amisulpride 100g,
Beta-schardinger dextrin-350g,
Microcrystalline Cellulose 63g,
Polyvinylpolypyrrolidone 18g,
Polyvinylpyrrolidone 16g is made into 10wt% polyvinylpyrrolidone aqueous solution and adds,
Magnesium stearate 6g,
Silicon dioxide 3g,
Process 1000 units altogether.
Preparation technology:
1) process 50 ℃ of saturated aqueous solutions by taking by weighing beta-schardinger dextrin-350g, put then in the homogenizer, open and stir, rotating speed is 1000 rev/mins; Get amisulpride 100g and be dissolved in the 3000ml ethanol, be added drop-wise to then in the beta-schardinger dextrin-saturated aqueous solution that stirs, rate of addition is 2ml/ minute, and constant temperature stirred 1 hour; Stop heating and continue to be stirred to room temperature, stop after 3 hours stirring, spray drying makes Benexate Hydrochloride;
2) Benexate Hydrochloride that makes is crossed 100 mesh sieves; Make soft material with 10wt% polyvidone aqueous solution (binding agent) then with behind diluents microcrystalline cellulose, the disintegrating agent polyvinylpolypyrrolidone mix homogeneously; Cross 12-28 mesh sieve system wet granular; Granule is put 50-70 ℃ of intensive drying, cross 10-24 mesh sieve granulate and must do granule, add magnesium stearate lubricant and silicon dioxide and always mix;
3) will always mix the gained granule carries out tabletting and gets tablet;
Perhaps, will always mix the particles filled capsule of gained and get capsule, perhaps direct packaging gets granule.
Embodiment 2: amisulpride oral formulations prescription:
Supplementary material title consumption
Amisulpride 100g,
Beta-schardinger dextrin-250g,
Lactose 199g,
Cross-linked carboxymethyl cellulose is received 21g,
Hydroxypropyl emthylcellulose 3g is made into 2wt% hydroxypropyl emthylcellulose aqueous solution and adds,
Pulvis Talci 30g,
Process 1000 units altogether.
Preparation technology
1) take by weighing beta-schardinger dextrin-by recipe quantity and process 50 ℃ of saturated aqueous solutions, put then in the homogenizer, open and stir, rotating speed is 1500 rev/mins; The amisulpride of recipe quantity is dissolved in the 3000ml ethanol, is added drop-wise to then in the beta-schardinger dextrin-saturated aqueous solution that stirs, speed is 2ml/ minute, and constant temperature stirred 30 minutes.Stop heating and continue to be stirred to room temperature, stop after 2.5 hours stirring, spray drying makes Benexate Hydrochloride;
2) Benexate Hydrochloride that makes is crossed 100 mesh sieves; Then with diluent, disintegrating agent mix homogeneously after with 2% hypromellose aqueous solution system soft material; Cross 12-28 mesh sieve system wet granular; Granule is put 50-70 ℃ of intensive drying, cross 10-24 mesh sieve granulate and must do granule, add lubricant and always mix;
3) the gained granule is carried out tabletting gets tablet, filled capsules gets capsule or direct packaging gets granule.
Embodiment 3: supplementary material title consumption
Amisulpride 100g,
Alpha-cyclodextrin 200g,
Pregelatinized Starch 240g,
Carboxymethyl starch is received 30g,
Hydroxypropyl cellulose 5g is made into the solution that contains the 5wt% hydroxypropyl cellulose with the ethanol of concentration 75wt% and adds,
Pulvis Talci 30g,
Process 1000 units altogether.
Preparation technology
1) takes by weighing alpha-cyclodextrin by recipe quantity and add suitable quantity of water and be ground to pasty state, pour in the colloid mill, open machine; The amisulpride of recipe quantity is dissolved in the 3000ml ethanol, is added drop-wise to then in the ground pasty state alpha-cyclodextrin, speed is 3ml/ minute, continues to grind 30 minutes, and spray drying makes the alpha-cyclodextrin clathrate;
2) the alpha-cyclodextrin clathrate that makes is crossed 100 mesh sieves; Use the 75% alcoholic solution system soft material that contains the 5wt% hyprolose then with behind diluent, the disintegrating agent mix homogeneously; Cross 12-28 mesh sieve system wet granular; Granule is put 50-70 ℃ of intensive drying, cross 10-24 mesh sieve granulate and must do granule, add lubricant and always mix;
3) the gained granule is carried out tabletting gets tablet, filled capsules gets capsule or direct packaging gets granule.
Embodiment 4: amisulpride oral formulations prescription:
Supplementary material title consumption
Amisulpride 200g,
Alpha-cyclodextrin 100g,
Pregelatinized Starch 120g,
Microcrystalline Cellulose 150g,
Polyvinylpolypyrrolidone 21g,
Xanthan gum 3g is mixed with the 2wt% xanthan gum solution and adds,
Magnesium stearate 9g,
Process 1000 units altogether.
Preparation technology
1) takes by weighing alpha-cyclodextrin by recipe quantity and add suitable quantity of water and be ground to pasty state, pour in the colloid mill, open machine; The amisulpride of recipe quantity is dissolved in the 6000ml ethanol, is added drop-wise to then in the ground pasty state alpha-cyclodextrin, speed is 3ml/ minute, continues to grind 30 minutes, and spray drying makes the alpha-cyclodextrin clathrate;
2) the alpha-cyclodextrin clathrate that makes is crossed 100 mesh sieves; Then with diluent, disintegrating agent mix homogeneously after with 2% xanthan gum solution system soft material, cross 12-28 mesh sieve system wet granular, granule is put 50-70 ℃ of intensive drying; Cross 10-24 mesh sieve granulate and must do granule, add lubricant and always mix;
3) the gained granule is carried out tabletting gets tablet, filled capsules gets capsule or direct packaging gets granule.
Embodiment 5: supplementary material title consumption
Amisulpride 100g,
Gamma-cyclodextrin 250g,
Lactose 137g,
Microcrystalline Cellulose 80g,
Carboxymethyl starch is received 24g,
Xanthan gum 3g is made into the 2wt% xanthan gum solution and adds,
Magnesium stearate 9g,
Process 1000 units altogether.
Preparation technology
1) takes by weighing gamma-cyclodextrin by recipe quantity and add suitable quantity of water and be ground to pasty state, pour in the colloid mill, open machine; The amisulpride of recipe quantity is dissolved in the 3000ml ethanol, is added drop-wise to then in the ground pasty state gamma-cyclodextrin, speed is 3ml/ minute, continues to grind 30 minutes, and spray drying makes the alpha-cyclodextrin clathrate;
2) the gamma-cyclodextrin clathrate that makes is crossed 100 mesh sieves; Then with diluent, disintegrating agent mix homogeneously after with 2% xanthan gum solution system soft material, cross 12-28 mesh sieve system wet granular, granule is put 50-70 ℃ of intensive drying; Cross 10-24 mesh sieve granulate and must do granule, add lubricant and always mix;
3) the gained granule is carried out tabletting and get tablet, perhaps filled capsules gets capsule, and perhaps direct packaging gets granule.
Comparative Examples 1: supplementary material title consumption
Amisulpride 100g,
Lactose 120g,
Microcrystalline Cellulose 63.5g,
Carboxymethyl starch is received 12g,
Hydroxypropyl emthylcellulose 1g is made into 2wt% hydroxypropyl emthylcellulose aqueous solution and adds,
Magnesium stearate 4.5g,
Process 1000 units altogether.
Step of preparation process is following:
1) amisulpride and other adjuvants are dried to moisture＜3.0% for 50-70 ℃, it is subsequent use to cross 100 mesh sieves.
2) take by weighing amisulpride, diluent, disintegrating agent by recipe quantity and put in the quick mixer granulator behind the mix homogeneously, with 2% hydroxypropyl emthylcellulose aqueous solution system soft material, 24 mesh sieves are granulated.
3) wet granular is put 50-70 ℃ of drying in the drying baker, and 20 mesh sieve granulate must be done granule, adds lubricant and always mixes, and the gained granule is carried out tabletting get tablet.
Further specify effect of the present invention through experiment below:
Test Example 1: the comparison of amisulpride cyclodextrin clathrate dissolubility in aqueous solution
Amisulpride cyclodextrin clathrate and each 50mg of reference substance amisulpride raw material of the preparation of embodiment 1-5 step 1); Put in the 50ml volumetric flask, thin up is to scale, and jolting is 1 hour under the room temperature; Measure dissolubility respectively with ultraviolet spectrophotometry, the result is as shown in table 1 below:
The different embodiment of table 1. and reference substance solubility results in water
Result of the test can find out that behind cyclodextrin inclusion compound, amisulpride dissolubility in water improves about 22-34 doubly.
Test Example 2: the tablet stripping characteristic of amisulpride cyclodextrin clathrate preparation is investigated
Adopting dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2010), is solvent with water, and rotating speed is 50 rev/mins; Temperature is 37.0 ± 0.5 ℃ of operations in accordance with the law; In the time of 10,15,20,30,45 minutes, taking liquid 10ml replenishes the water of equivalent simultaneously respectively; Medicinal liquid is crossed the membrane filtration of 0.45 μ m, and ultraviolet spectrophotometry is measured.
The conventional tablet of tablet for preparing among the embodiment 1-5 and Comparative Examples 1 preparation is carried out the investigation of stripping characteristic as stated above, and its stripping curve is seen Fig. 1.We can find out from figure, and amisulpride sheet of the present invention and amisulpride ordinary tablet (Comparative Examples 1) were accumulated dissolution all greater than 80% in the time of 30 minutes, meet the stripping requirement of tablet, and the tablet stripping of the present invention's preparation is steady, fast.Stripping fully basically in 20 minutes.These characteristics show that the tablet of the present invention's preparation can make the steady in vivo rapid release of medicine, not only make the curative effect of medication performance fast, and have effectively avoided the medicine peak valley phenomenon, reduce the untoward reaction that causes because of blood drug level is too high.
Test Example 3: the investigation of the tablet related substance (total impurities) of amisulpride cyclodextrin clathrate preparation
(1) influence factor's test
Get amisulpride tablet among the embodiment 1-5, put respectively illumination (4500LX ± 500LX), high temperature (60 ℃), high humidity (92.5%) condition held, it is as shown in table 2 to detect the related substance result respectively at sampling in the 5th day, 10 days:
Table 2. embodiment 1-5 and Comparative Examples 1 influence factor test and detect related substance (%)
(2) accelerated test
Amisulpride sheet among the embodiment 1-5 and Comparative Examples 1 amisulpride sheet are put 40 ℃ of temperature by commercially available back, placed 6 months in the climatic chamber of relative humidity 75%, and sampling detects related substance 1,2,3,6 the end of month, the result is as shown in table 3:
Different embodiment of table 3. and Comparative Examples accelerated test related substance be (%) relatively
| Time (moon) | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Comparative Examples 1 |
| 0 | 0.17 | 0.16 | 0.16 | 0.17 | 0.16 | 0.17 |
| 1 | 0.18 | 0.19 | 0.16 | 0.18 | 0.17 | 0.28 |
| 2 | 0.17 | 0.18 | 0.19 | 0.20 | 0.18 | 0.34 |
| 3 | 0.19 | 0.20 | 0.19 | 0.22 | 0.19 | 0.42 |
| 6 | 0.22 | 0.23 | 0.25 | 0.27 | 0.23 | 0.48 |
In amisulpride sheet influence factor test and the accelerated test, the character and the content of tablet do not change basically, can be found out by the result of the test of table 2 and table 3, and amisulpride sheet related substance of the present invention is far below Comparative Examples.Explain that the prepared granule of the present invention can improve stability of drug, prolong the storage life of preparation.
Claims (10)
1. amisulpride oral formulations contains the cyclodextrin and the pharmaceutically acceptable excipient of active drug amisulpride, enclose active drug; Wherein, amisulpride exists with the cyclodextrin clathrate form, and the mass ratio of amisulpride and cyclodextrin is 1: (0.5～4).
2. amisulpride oral formulations according to claim 1, the mass ratio that it is characterized in that said amisulpride and cyclodextrin is 1: (1～3.5).
3. amisulpride oral formulations according to claim 1 is characterized in that said cyclodextrin is selected from one or more in alpha-cyclodextrin, beta-schardinger dextrin-, the gamma-cyclodextrin; Preferred alpha-cyclodextrin, beta-schardinger dextrin-; Beta-schardinger dextrin-most preferably.
4. amisulpride oral formulations according to claim 1 is characterized in that said excipient comprises diluent, disintegrating agent, binding agent, lubricant; Preferably, the composition of amisulpride oral formulations mass ratio is:
Amisulpride 10%-50%, diluent 10%-50%, disintegrating agent 1%-10%, binding agent 0.5%-5%, lubricant 1%-5%, each composition sum is 100%; The dosage of cyclodextrin is that the mass ratio of amisulpride and cyclodextrin is 1: (0.5～4); The mass ratio of preferred amisulpride and cyclodextrin is 1: (1～3.5).
5. amisulpride oral formulations according to claim 4 is characterized in that said diluent is 15%-45%, and disintegrating agent is 3.0-5.0%, and binding agent is 0.5-3.0%, and lubricant is 1.5-5.0%.
6. amisulpride oral formulations according to claim 4 is characterized in that said diluent is selected from one or more in microcrystalline Cellulose, lactose, mannitol, the pregelatinized Starch;
Said disintegrating agent is selected from one or more in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, carboxymethyl starch sodium and the low-substituted hydroxypropyl cellulose;
Said binding agent is selected from copolyvidone, hydroxypropyl cellulose, polyvinylpyrrolidone, hydroxypropyl emthylcellulose, Radix Acaciae senegalis or xanthan gum;
Said lubricant is selected from one or more in magnesium stearate, Pulvis Talci, the silicon dioxide.
7. according to claim 1 or 4 described amisulpride oral formulations, it is characterized in that processing by following composition:
Polyvinylpyrrolidone 16g is made into 10wt% polyvinylpyrrolidone aqueous solution and adds,
Magnesium stearate 6g
Silicon dioxide 3g
Process 1000 units altogether.
8. according to claim 1 or 4 described amisulpride oral formulations, it is characterized in that processing by following composition:
Xanthan gum 3g is mixed with the 2wt% xanthan gum solution and adds
Magnesium stearate 9g
Process 1000 units altogether.
9. according to claim 1 or 4 described amisulpride oral formulations, it is characterized in that processing by following composition:
Hydroxypropyl cellulose 5g is made into the solution that contains the 5wt% hydroxypropyl cellulose with the ethanol of concentration 75wt% and adds,
Pulvis Talci 30g
Process 1000 units altogether.
10. the method for preparing of each said amisulpride oral formulations of claim 1-9 comprises the steps:
(1) cyclodextrin of recipe quantity is processed 50-60 ℃ of saturated aqueous solution, in blender, stir then, rotating speed is 750 rev/mins-1500 rev/mins; The amisulpride of recipe quantity is dissolved in an amount of ethanol; Be added drop-wise to then in the cyclodextrin saturated aqueous solution that stirs; The control rate of addition is 1-3ml/ minute, maintains the temperature at 50-60 ℃, rotating speed after being added dropwise to complete and continues for 750 rev/mins-1500 rev/mins to stir 4 hours, stops to stir; Spray drying makes the amisulpride cyclodextrin clathrate;
Perhaps,
The cyclodextrin of recipe quantity is added suitable quantity of water be developed into pasty state, pour in the colloid mill, grind; The amisulpride of recipe quantity is dissolved in an amount of ethanol, is added drop-wise to then in the ground pasty state cyclodextrin, the control rate of addition is 2-4ml/ minute, continues to grind 30-45 minute, and spray drying makes cyclodextrin clathrate;
(2) the amisulpride cyclodextrin clathrate that makes is crossed 100 mesh sieves; Add diluent, disintegrating agent, binding agent system soft material then, cross the 12-28 mesh sieve and make wet granular, with wet granular in 50-70 ℃ of intensive drying; Cross 10-24 mesh sieve granulate and must do granule, add lubricant and always mix;
(3) will always mix the gained granule and carry out that tabletting gets tablet, filled capsules gets capsule or direct packaging gets granule.
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| CN104902876A (en) * | 2012-11-30 | 2015-09-09 | 葛兰素史克公司 | Novel pharmaceutical composition |
| CN108926528A (en) * | 2017-05-25 | 2018-12-04 | 北京万全德众医药生物技术有限公司 | Liquid oral compositions containing Amisulpride resinate |
| US10800738B2 (en) | 2017-12-05 | 2020-10-13 | Sunovion Pharmaceuticals Inc. | Crystal forms and production methods thereof |
| CN111821337A (en) * | 2020-08-30 | 2020-10-27 | 扬子江药业集团广州海瑞药业有限公司 | Process for preparing pharmaceutical composition |
| US10874639B2 (en) | 2017-12-05 | 2020-12-29 | Sunovion Pharmaceuticals Inc. | Nonracemic mixtures and uses thereof |
| US11160758B2 (en) | 2019-06-04 | 2021-11-02 | Sunovion Pharmaceuticals Inc. | Modified release formulations and uses thereof |
| CN115300471A (en) * | 2022-10-12 | 2022-11-08 | 则正(济南)生物科技有限公司 | Orally disintegrating amisulpride tablet and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104902876A (en) * | 2012-11-30 | 2015-09-09 | 葛兰素史克公司 | Novel pharmaceutical composition |
| CN104902876B (en) * | 2012-11-30 | 2018-01-19 | 葛兰素史克公司 | New pharmaceutical composition |
| CN108926528A (en) * | 2017-05-25 | 2018-12-04 | 北京万全德众医药生物技术有限公司 | Liquid oral compositions containing Amisulpride resinate |
| US10800738B2 (en) | 2017-12-05 | 2020-10-13 | Sunovion Pharmaceuticals Inc. | Crystal forms and production methods thereof |
| US10874639B2 (en) | 2017-12-05 | 2020-12-29 | Sunovion Pharmaceuticals Inc. | Nonracemic mixtures and uses thereof |
| US11370753B2 (en) | 2017-12-05 | 2022-06-28 | Sunovion Pharmaceuticals Inc. | Crystal forms and production methods thereof |
| US11517558B2 (en) | 2017-12-05 | 2022-12-06 | Sunovion Pharmaceuticals Inc. | Nonracemic mixtures and uses thereof |
| US11767293B2 (en) | 2017-12-05 | 2023-09-26 | Sunovion Pharmaceuticals Inc. | Crystal forms and production methods thereof |
| US11160758B2 (en) | 2019-06-04 | 2021-11-02 | Sunovion Pharmaceuticals Inc. | Modified release formulations and uses thereof |
| US11654113B2 (en) | 2019-06-04 | 2023-05-23 | Sunovion Pharmaceuticals Inc. | Modified release formulations and uses thereof |
| CN111821337A (en) * | 2020-08-30 | 2020-10-27 | 扬子江药业集团广州海瑞药业有限公司 | Process for preparing pharmaceutical composition |
| CN115300471A (en) * | 2022-10-12 | 2022-11-08 | 则正(济南)生物科技有限公司 | Orally disintegrating amisulpride tablet and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN102600132B (en) | 2014-05-14 |
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