CN103784426A - Aripiprazole oral membrane and preparation method thereof - Google Patents
Aripiprazole oral membrane and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an aripiprazole oral membrane and a preparation method thereof. The aripiprazole oral membrane contains cyclodextrin encapsulated aripiprazole, wherein the cyclodextrin is more than one of hydroxypropyl-beta-cyclodextrin and glucosyl-beta-cyclodextrin, and the weight ratio of the cyclodextrin to the aripiprazole is 1: 1 to 3: 1. The membrane preparation has the beneficial effects of even, smooth and clean membrane obtained, easy administration and direct administration without water, quick and safe dissolving-out, high absorption speed, high bioavailability, good curative effect, simple production process, low production cost, and high added value of products. The aripiprazole membrane is quick to dissolve out, good in stability and high in bioavailability, and excellent in bioavailability, and also good in compliance and popular with patients; the aripiprazole membrane is good in formability, and capable of directly adhering to the part to which the medicine is applied after administration, and thus cannot be spitted, and therefore, psychopaths can be prevented from spitting out and hiding the drug; and in the production process, almost no dust flies, and the problems of labor protection and environmental pollution can be solved.
Description
Technical field
The present invention relates to aripiprazole formulations, be specifically related to a kind of medicine film preparation and preparation method thereof.
Background technology
Aripiprazole belongs to third generation atypical antipsychotic agents, the schizophrenia positive and negative symptoms are all had to significant curative effect, and side effect is very little.Existing listing dosage form is take conventional tablet and oral cavity disintegration tablet as main.During due to schizophrenic's medication, often there is Tibetan medicine and tell medicine phenomenon, greatly having affected curative effect of medication.Making membrane does not need with water delivery service, is placed on tongue instantly, and sticks at this place and is difficult for spuing, and has therefore improved the compliance of clinical application, is particularly suitable for psychotic; And production technology is simple, power consumption is few, and cost is lower.
Medicine film preparation is as far back as i.e. existing much research of nineteen seventies, as tranquilizer film (Chinese Journal of Pharmaceuticals, 1976,12(19)), diphenoxylate medicine film (Chinese Journal of Pharmaceuticals, 1976,12(22)), external applied contraceptive film (Chinese Journal of Pharmaceuticals, 1977,4-5(45)), nitroglycerin medicine film (Chinese Journal of Pharmaceuticals, 1977,12(5)), rhodexin film (Chinese Journal of Pharmaceuticals, 1980,4(18)), clonidine sustained release film formulation (Chinese Journal of Pharmaceuticals, 1981,3(141)) etc.Chinese Pharmacopoeia is also recorded (Pharmacopoeia of People's Republic of China 1995 editions, 2000 editions, 2005 editions, 2010 editions) using membrane as official preparation.
Patent about membrane also emerges in an endless stream, there is the edible water-soluble film (CN101516331A) that contains foam reducing flavoring agent, for the film bandage (CN101389309A) of mucosal administration of actives, high dose film compositions and preparation method thereof (CN101616660A), polymer-based films and drug delivery system prepared therefrom (CN101668519A), the preparation method (CN101744791A) of edible film, the film (CN101346135A) of the adjusted pH sending for activating agent, for the film bandage (CN101389309A) of mucosal administration of actives, non-mucoadhesive film dosage forms (CN101626756A), disintegrable oral films (CN101384249A), membrane (CN101621990A) that can be Orally administered, for neuroleptic, the oral fast that can not be spued collapses film (CN101287445A), instant capacity membrane (CN100396332C) etc.The inventor has also applied for that surface establishes the patent of the new packaged form of the packaging machine of the production machine of dapple medicinal film agent (CN201596139U), microporous sponge shape medicine film preparation (CN102028672B) and membrane, membrane, membrane, to promote membrane development at home.
The poorly water-soluble of Aripiprazole is (under room temperature, dissolubility <1 μ g/ml), while preparing membrane, have and disperse problem uneven and can not Fast Stripping, need to improve its solubility property improves uniformity, accelerates drug-eluting, thereby raising bioavailability, safety and the effectiveness of assurance medicine.Increasing drug solubility, enhanced stability and taste masking by the clathration of cyclodextrin is a kind of known method.CN100335047C discloses a kind of aqueous injectable of Aripiprazole, and wherein Aripiprazole enclose forms inclusion complex in beta-schardinger dextrin-, and the weight ratio of beta-schardinger dextrin-and Aripiprazole is 10:1～100:1, and the pH of preparation is 3.5 to 5.But membrane is thin, light, little, because a mouthful molten film need to dissolve rapidly conventionally in mouth, so weight can not be too large; If gain in weight: or film is too large, uses inconvenience; Or film is too thick, cannot dissolve rapidly.Thereby the weight of a slice film is generally below 100mg, is generally 20～60mg.The dosage of Aripiprazole be 5mg or 10mg(conventionally account for solid amount in film 10～25%); In prescription, macromolecule filming material at least needs to account for the more than 30% of total solid in film conventionally, otherwise physical strength does not reach instructions for use; So the amount of the cyclodextrin that can add in prescription is subject to certain restrictions.If add enough cyclodextrin, improve the solubility property of medicine, will reduce the consumption of macromolecule filming material in prescription, the physical property of the film making can not meet the demands, can be very crisp, easy fracture, fragmentation.
Summary of the invention
The object of the present invention is to provide molten membrane of a kind of Aripiprazole mouth and preparation method thereof, the above-mentioned defect existing to overcome prior art.
The molten membrane of Aripiprazole mouth of the present invention, the Aripiprazole that contains cyclodextrin parcel, wherein:
Described cyclodextrin is more than one in HP-β-CD or glucose group-beta-cyclodextrin, and the weight ratio of cyclodextrin and Aripiprazole is 1:1～3:1, preferably 1.2:1～1.5:1;
The method of cyclodextrin parcel Aripiprazole, comprises the steps:
By cyclodextrin and hydrochloric acid solution mixed dissolution, add Aripiprazole, stir 0.5～1.5h at 55～65 ℃, can obtain the Aripiprazole of described cyclodextrin parcel;
The concentration of described hydrochloric acid solution is 0.08M～0.12M, preferably 0.1M;
The w/v of the weight of cyclodextrin and described hydrochloric acid solution is:
Cyclodextrin: hydrochloric acid solution=1g: 0.9～1.1ml;
Preferably: cyclodextrin: hydrochloric acid solution=1g: 1ml;
Preferably, the described molten membrane of Aripiprazole mouth, comprises the component of following percentage by weight:
The Aripiprazole 20～70% of cyclodextrin parcel
Macromolecule filming material 30～80%
The percentage ratio sum of said components content is 100%;
Described macromolecule filming material comprises more than one in hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), sodium alginate, polyoxyethylene (PEO), Bletilla glucomannan, corn starch or carrageenan; Preferably HPMC, HPC, PVA or PEO.
Described other adjuvants comprise plasticizer, as PEG, glycerol or Tween 80 etc.; Correctives, as sweeting agent, acidic flavoring agent, aromatic, gummy macromolecular material, lecithin, cephalin, phosphatidic acid, pigment, antioxidant or antiseptic etc.
Preferably, the described molten membrane of Aripiprazole mouth, comprises the component of following percentage by weight:
The Aripiprazole 30～50% of cyclodextrin parcel
Macromolecule filming material 45～70%
The percentage ratio sum of said components content is 100%.
Described cyclodextrin is the one of HP-β-CD or glucose group-beta-cyclodextrin;
Described macromolecule filming material comprises more than one in hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), sodium alginate, polyoxyethylene (PEO), Bletilla glucomannan, corn starch or carrageenan; Preferably HPMC, PVA or PEO.
Described other adjuvants comprise plasticizer, as PEG, glycerol or Tween 80 etc.; Correctives, comprises sweeting agent, acidic flavoring agent, aromatic, gummy macromolecular material, lecithin, cephalin or phosphatidic acid etc.; And pigment, antioxidant or antiseptic etc.
The preparation method of the molten membrane of Aripiprazole mouth of the present invention, comprises the steps:
(1) by cyclodextrin and hydrochloric acid solution mixed dissolution, add Aripiprazole, stir 0.5～1.5h at 55～65 ℃, can obtain the Aripiprazole of described cyclodextrin parcel;
The concentration of described hydrochloric acid solution is 0.08M～0.12M, preferably 0.1M;
The w/v of the weight of cyclodextrin and described hydrochloric acid solution is:
Cyclodextrin: hydrochloric acid solution=1g: 0.9～1.1ml;
Preferably: cyclodextrin: hydrochloric acid solution=1g: 1ml;
The concentration of described hydrochloric acid solution is 0.08M～0.12M, preferably 0.1M;
(2) add purified water and other adjuvants, stir into full-bodied solution, cross 60～100 mesh sieves, remove insoluble matter, vacuum defoamation;
(3) then by above-mentioned solution extension in stainless steel band, 60～90 ℃ dry 10～20 minutes, obtain the described molten membrane of Aripiprazole mouth.
Inventor is through a large amount of experimental studies have found that, HP-β-CD or glucose group-beta-cyclodextrin are best to the enclose effect of medicine, in the time of enclose, when the ratio of cyclodextrin and described hydrochloric acid solution is cyclodextrin: hydrochloric acid solution=1g: 0.9～1.1ml, preferably: cyclodextrin: hydrochloric acid solution=1g: when 1ml, at 55～65 ℃, stir 0.5～1.5h enclose best results, by under so specific condition, pharmaceutical pack is combined in cyclodextrin, and the ratio of cyclodextrin and medicine can be controlled in 1:1～3:1.Like this, the membrane that clathrate mixes, prepares with macromolecule filming material, its stripping and physical property all can meet the requirement of clinical application.
The beneficial effect of membranaceous preparation of the present invention is: the film making is even, bright and clean; Take simply, do not need drinking-water to take; Stripping rapidly, completely; And infiltration rate is fast, bioavailability is high, good effect; Production technology is simple, and production cost is low, and added value of product is high.Aripiprazole membrane of the present invention stripping rapidly, good stability, bioavailability be high, has good biological effectiveness; Compliance is good, welcome by patient; Formability is good, after administration, can directly attach to medicine-feeding part, cannot spue, and can avoid psychosis to tell medicine, Tibetan medicine; Several without dust from flying in process of production, may solve labor protection and problem of environmental pollution.
Fig. 1 is the stripping curve of embodiment 1.
Fig. 2 is the stripping curve of embodiment 2.
Fig. 3 is comparative example 1 stripping curve.
Fig. 4 is comparative example 2 stripping curve.
Fig. 5 is comparative example 3 stripping curve.
The specific embodiment
Embodiment 1
Prescription:
Preparation method:
Get the 0.1M hydrochloric acid solution that HP-β-CD adds 30ml, stirring and dissolving, then add Aripiprazole, stirs 1h at 60 ℃, add subsequently purified water 300ml, then add titanium dioxide, HPMC and HPC, be stirred into full-bodied solution, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Again by the extension of film liquid on stainless steel band, 80 ℃ of dry 15min.According to assay result, cut into after certain size, peel off from stainless steel band, pack and get final product.
The medicine film preparation obtaining, thickness is 0.065mm, every containing Aripiprazole 5mg or 10mg.Oral every day 1 time, first week is initial dose 5mg/ day, and second week increases to 10mg/ day, and medication, after 2 weeks, can increase dosage according to individual curative effect and tolerance situation, and every day, maximal dose should not exceed 30mg.
This mouthful of molten film outward appearance is even, bright and clean.Possess enough intensity and toughness, physical strength meets the demands.
Determination of Content Uniformity: get 1 of this product, put in 100ml measuring bottle, add mobile phase and dissolve, be diluted to scale, shake up, place, get supernatant liquid filtering, get subsequent filtrate as need testing solution, with HPLC method mensuration content, and press two appendix X E of Chinese Pharmacopoeia version in 2010 and measure uniformity of dosage units (A+1.80S answers≤20.0).The results are shown in Table 1.Result shows, the molten film content of the Aripiprazole mouth uniformity of preparation is better.
Table 1 embodiment 1 Determination of Content Uniformity result
| Uniformity of dosage units test sample | Content (%) |
| 1 | 100.03 |
| 2 | 98.20 |
| 3 | 98.74 |
| 4 | 98.52 |
| 5 | 99.31 |
| 6 | 101.20 |
| 7 | 100.39 |
| 8 | 100.60 |
| 9 | 98.69 |
| 10 | 99.10 |
| Meansigma methods | 99.5 |
| RSD | 1.0% |
| A+1.8*S | 2.3 |
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take pH4.0 acetate buffer solution 500ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 1,2,5,10,15,30 and 60 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate the stripping quantity of every according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).Its In Vitro Dissolution curve is shown in Fig. 1.As seen from Figure 1, the In Vitro Dissolution of the molten film of Aripiprazole mouth of the present invention is very fast, and in 3min, stripping more than 85%, is dissolved completely when 5min.
Embodiment 2
Prescription:
Preparation method:
Get the 0.1M hydrochloric acid solution that glucose group-beta-cyclodextrin adds 24ml, stirring and dissolving, then add Aripiprazole, stirs 1h at 60 ℃, add subsequently purified water 300ml, then add all the other adjuvants, be stirred into full-bodied solution, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Again by the extension of film liquid on stainless steel band, 90 ℃ of dry 15min.According to assay result, cut into after certain size, peel off from stainless steel band, pack and get final product.
The medicine film preparation obtaining, thickness is 0.065mm, every containing Aripiprazole 5mg or 10mg.Oral every day 1 time, first week is initial dose 5mg/ day, and second week increases to 10mg/ day, and medication, after 2 weeks, can increase dosage according to individual curative effect and tolerance situation, and every day, maximal dose should not exceed 30mg.
This mouthful of molten film outward appearance is even, bright and clean.Possess enough intensity and toughness, physical strength meets the demands.
Determination of Content Uniformity: get 1 of this product, put in 100ml measuring bottle, add mobile phase and dissolve, be diluted to scale, shake up, place, get supernatant liquid filtering, get subsequent filtrate as need testing solution, with HPLC method mensuration content, and press two appendix X E of Chinese Pharmacopoeia version in 2010 and measure uniformity of dosage units (A+1.80S answers≤20.0).The results are shown in Table 2.Result shows, the molten film content of the Aripiprazole mouth uniformity of preparation is better.
Table 2 embodiment 2 Determination of Content Uniformity results
| Uniformity of dosage units test sample | Content (%) |
| 1 | 99.97 |
| 2 | 100.29 |
| 3 | 101.38 |
| 4 | 101.56 |
| 5 | 101.22 |
| 6 | 102.52 |
| 7 | 100.90 |
| 8 | 100.48 |
| 9 | 102.33 |
| 10 | 100.45 |
| Meansigma methods | 101.1 |
| RSD | 0.8% |
| A+1.8*S | 2.7 |
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take pH4.0 acetate buffer solution 500ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 1,2,5,10,15,30 and 60 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate the stripping quantity of every according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).Its In Vitro Dissolution curve is shown in Fig. 2.As seen from Figure 2, the In Vitro Dissolution of the molten film of Aripiprazole mouth of the present invention is very fast, and in 3min, stripping is more than 80%.When 5min, substantially dissolve completely.
Comparative example 1
Prescription is with embodiment 1.
Preparation method:
Get HP-β-CD and add the purified water of 30ml, stirring and dissolving, then add Aripiprazole, all the other are with embodiment 1.
The medicine film preparation obtaining, thickness is about 0.065mm, and every containing Aripiprazole 5mg or 10mg.
This mouthful of molten film possesses certain intensity and toughness, and physical strength meets the demands substantially.But outward appearance is inhomogeneous, visible insoluble granule.
Measure uniformity of dosage units according to method described in embodiment 1, the results are shown in Table 3.Result shows, the molten film of Aripiprazole mouth of preparing according to the present embodiment method, and content uniformity is poor.
Table 3 comparative example 1 Determination of Content Uniformity result
| Uniformity of dosage units test sample | Content (%) |
| 1 | 99.11 |
| 2 | 110.25 |
| 3 | 105.24 |
| 4 | 103.22 |
| 5 | 102.52 |
| 6 | 98.53 |
| 7 | 95.22 |
| 8 | 92.13 |
| 9 | 91.00 |
| 10 | 107.69 |
| Meansigma methods | 100.5 |
| RSD | 6.4% |
| A+1.8*S | 12.1 |
Get 6 of this product, measure In Vitro Dissolution curve according to method described in embodiment 1, the results are shown in Figure 3.As seen from Figure 3, the molten film of Aripiprazole mouth of preparing according to the present embodiment method, when 10min, stripping more than 80%, is dissolved completely after 30min.In Vitro Dissolution is slower, has larger difference with embodiment 1.
Comparative example 2
Prescription is with embodiment 1.
Preparation method:
Get the 0.1M hydrochloric acid solution that HP-β-CD adds 330ml, stirring and dissolving, then add Aripiprazole, stirs 1h at 60 ℃, adds subsequently titanium dioxide, HPMC and HPC, and all the other are with embodiment 1.
The medicine film preparation obtaining, thickness is about 0.065mm, and every containing Aripiprazole 5mg or 10mg.
This mouthful of molten film possesses certain intensity and toughness, and physical strength meets the demands substantially.But outward appearance is inhomogeneous, visible insoluble granule.
Measure uniformity of dosage units according to method described in embodiment 1, the results are shown in Table 4.Result shows, the molten film of Aripiprazole mouth of preparing according to the present embodiment method, and content uniformity is poor.
Table 4 comparative example 2 Determination of Content Uniformity results
| Uniformity of dosage units test sample | Content (%) |
| 1 | 109.11 |
| 2 | 97.52 |
| 3 | 99.65 |
| 4 | 101.53 |
| 5 | 106.23 |
| 6 | 100.24 |
| 7 | 93.26 |
| 8 | 96.78 |
| 9 | 107.67 |
| 10 | 103.24 |
| Meansigma methods | 101.5 |
| RSD | 5.0% |
| A+1.8*S | 10.7 |
Get 6 of this product, measure In Vitro Dissolution curve according to method described in embodiment 1, the results are shown in Figure 4.As seen from Figure 4, the molten film of Aripiprazole mouth of preparing according to the present embodiment method, when 15min, stripping more than 80%, is dissolved completely after 30min.In Vitro Dissolution is slower, has larger difference with embodiment 1.
Comparative example 3
Prescription:
Aripiprazole 20g
HP-β-CD 62g
HPMC 18g
Preparation method:
Get HP-β-CD and add the purified water of 330ml, stirring and dissolving, then add Aripiprazole, stirs 1h at 60 ℃, then adds HPMC, and high-speed stirred evenly becomes full-bodied solution, and all the other are with embodiment 1.
The medicine film preparation obtaining, thickness is about 0.065mm, and every containing Aripiprazole 5mg or 10mg.
This mouthful of molten film outward appearance is more even, but film is very crisp, cuts, frangible while packing, easily split, yield rate is low.
Measure uniformity of dosage units according to method described in embodiment 1, the results are shown in Table 5.Result shows, the molten film of Aripiprazole mouth of preparing according to the present embodiment method, and content uniformity can meet the demands.
Table 5 comparative example 3 Determination of Content Uniformity results
| Uniformity of dosage units test sample | Content (%) |
| 1 | 100.23 |
| 2 | 98.56 |
| 3 | 103.26 |
| 4 | 101.54 |
| 5 | 99.14 |
| 6 | 100.52 |
| 7 | 101.77 |
| 8 | 102.35 |
| 9 | 97.67 |
| 10 | 102.11 |
| Meansigma methods | 100.7 |
| RSD | 1.8% |
| A+1.8*S | 4.0 |
Get 6 of this product, measure In Vitro Dissolution curve according to method described in embodiment 1, the results are shown in Figure 5.As seen from Figure 5, the molten film of Aripiprazole mouth of preparing according to the present embodiment method, when 10min, stripping more than 80%, is dissolved completely after 15min.In Vitro Dissolution is slower than embodiment 1.
Claims (10)
1. the molten membrane of Aripiprazole mouth, is characterized in that, the Aripiprazole that contains cyclodextrin parcel, wherein:
Described cyclodextrin is more than one in HP-β-CD or glucose group-beta-cyclodextrin, and the weight ratio of cyclodextrin and Aripiprazole is 1:1～3:1.
2. the molten membrane of Aripiprazole mouth according to claim 1, is characterized in that the weight ratio 1.2:1～1.5:1 of cyclodextrin and Aripiprazole.
3. the molten membrane of Aripiprazole mouth according to claim 1 and 2, is characterized in that, the method for cyclodextrin parcel Aripiprazole, comprises the steps:
By cyclodextrin and hydrochloric acid solution mixed dissolution, add Aripiprazole, stir 0.5～1.5h at 55～65 ℃, can obtain the Aripiprazole of described cyclodextrin parcel;
The concentration of described hydrochloric acid solution is 0.08M～0.12M;
The w/v of the weight of cyclodextrin and described hydrochloric acid solution is:
Cyclodextrin: hydrochloric acid solution=1g: 0.9～1.1ml.
4. the molten membrane of Aripiprazole mouth, is characterized in that, comprises the component of following percentage by weight:
The Aripiprazole 20～70% of cyclodextrin parcel
Macromolecule filming material 30～80%
Other adjuvant 0～20%
The percentage ratio sum of said components content is 100%; Wherein:
Described cyclodextrin is more than one in HP-β-CD or glucose group-beta-cyclodextrin, and the weight ratio of cyclodextrin and Aripiprazole is 1:1～3:1;
The method of the Aripiprazole of cyclodextrin parcel, comprises the steps:
By cyclodextrin and hydrochloric acid solution mixed dissolution, add Aripiprazole, stir 0.5～1.5h at 55～65 ℃, can obtain the Aripiprazole of described cyclodextrin parcel;
The concentration of described hydrochloric acid solution is 0.08M～0.12M;
The w/v of the weight of cyclodextrin and described hydrochloric acid solution is:
Cyclodextrin: hydrochloric acid solution=1g: 0.9～1.1ml.
5. the molten membrane of Aripiprazole mouth according to claim 4, is characterized in that the weight ratio 1.2:1～1.5:1 of cyclodextrin and Aripiprazole.
6. the molten membrane of Aripiprazole mouth according to claim 4, it is characterized in that, described macromolecule filming material comprises more than one in hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), sodium alginate, polyoxyethylene (PEO), Bletilla glucomannan, corn starch or carrageenan.
7. the molten membrane of Aripiprazole mouth according to claim 4, is characterized in that, described other adjuvants comprise plasticizer, as PEG, glycerol or Tween 80 etc.; Correctives, as sweeting agent, acidic flavoring agent, aromatic, gummy macromolecular material, lecithin, cephalin, phosphatidic acid, pigment, antioxidant or antiseptic.
8. the molten membrane of Aripiprazole mouth according to claim 4, is characterized in that, comprises the component of following percentage by weight:
The Aripiprazole 30～50% of cyclodextrin parcel
Macromolecule filming material 45～70%
Other adjuvant 0～5%
The percentage ratio sum of said components content is 100%.
9. according to the preparation method of the molten membrane of Aripiprazole mouth described in claim 1～8 any one, comprise the steps:
(1) by cyclodextrin and hydrochloric acid solution mixed dissolution, add Aripiprazole, stir 0.5～1.5h at 55～65 ℃, can obtain the Aripiprazole of described cyclodextrin parcel;
The concentration of described hydrochloric acid solution is 0.08M～0.12M;
The w/v of the weight of cyclodextrin and described hydrochloric acid solution is:
Cyclodextrin: hydrochloric acid solution=1g: 0.9～1.1ml;
The concentration of described hydrochloric acid solution is 0.08M～0.12M;
(2) add purified water and other adjuvants, stir into solution, cross 60～100 mesh sieves, remove insoluble matter, vacuum defoamation;
(3) then by above-mentioned solution extension in stainless steel band, 60～90 ℃ dry 10～20 minutes, obtain the described molten membrane of Aripiprazole mouth.
10. method according to claim 9, is characterized in that, the concentration of described hydrochloric acid solution is 0.1M; The w/v of the weight of cyclodextrin and described hydrochloric acid solution is: cyclodextrin: hydrochloric acid solution=1g: 1ml.
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| CN107375945A (en) * | 2017-08-29 | 2017-11-24 | 沈阳药科大学 | A kind of donepezil cyclodextrin inclusion compound and the oral instant film containing this inclusion compound |
| US11331315B2 (en) | 2020-09-21 | 2022-05-17 | Xiamen Lp Pharmaceutical Co., Ltd. | Aripiprazole oral soluble film |
| WO2022247883A1 (en) * | 2021-05-26 | 2022-12-01 | 上海博志研新药物技术有限公司 | Cariprazine oral dissolving film composition and preparation method therefor and application thereof |
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| CN105078910A (en) * | 2015-09-22 | 2015-11-25 | 成都欣捷高新技术开发有限公司 | Freeze-dried oral preparation containing elopiprazole and preparation method of freeze-dried oral preparation |
| CN105078910B (en) * | 2015-09-22 | 2018-05-22 | 成都欣捷高新技术开发有限公司 | It is a kind of containing according to lyophilized oral formulations of piperazine azoles and preparation method thereof |
| CN107375945A (en) * | 2017-08-29 | 2017-11-24 | 沈阳药科大学 | A kind of donepezil cyclodextrin inclusion compound and the oral instant film containing this inclusion compound |
| US11331315B2 (en) | 2020-09-21 | 2022-05-17 | Xiamen Lp Pharmaceutical Co., Ltd. | Aripiprazole oral soluble film |
| US11701352B2 (en) | 2020-09-21 | 2023-07-18 | Xiamen Lp Pharmaceutical Co., Ltd. | Process for preparing aripiprazole oral soluble film |
| WO2022247883A1 (en) * | 2021-05-26 | 2022-12-01 | 上海博志研新药物技术有限公司 | Cariprazine oral dissolving film composition and preparation method therefor and application thereof |
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| Publication number | Publication date |
|---|---|
| CN103784426B (en) | 2015-11-18 |
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