CN103356512A - Benzenesulfonic acid amlodipine membranaceous preparation - Google Patents
Benzenesulfonic acid amlodipine membranaceous preparation Download PDFInfo
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- CN103356512A CN103356512A CN2013102720248A CN201310272024A CN103356512A CN 103356512 A CN103356512 A CN 103356512A CN 2013102720248 A CN2013102720248 A CN 2013102720248A CN 201310272024 A CN201310272024 A CN 201310272024A CN 103356512 A CN103356512 A CN 103356512A
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Abstract
The invention discloses a benzenesulfonic acid amlodipine membranaceous preparation which comprises a strip-shaped membrane zone and an effective therapic dose of benzenesulfonic acid amlodipine, wherein the benzenesulfonic acid amlodipine is loaded on the strip-shaped membrane zone; the strip-shaped membrane zone comprises an acidic strip-shaped membrane zone and an alkaline strip-shaped membrane zone; the acidic strip-shaped membrane zone and the alkaline strip-shaped membrane zone are connected into an integer and mutually alternately arranged; the acidic strip-shaped membrane zone takes a high-water solubility high-molecular film-forming material as a main part and contains 1%-20% of acidic agents in terms of the weight of the acidic strip-shaped membrane zone; the alkaline strip-shaped membrane zone takes the high-water solubility high-molecular film-forming material as the main part and contains 1%-20% of alkaline agents in terms of the weight of the alkaline strip-shaped membrane zone. The benzenesulfonic acid amlodipine membranaceous preparation disclosed by the invention becomes an effervescent membrane after meeting water, masks the odour by paralyzing olfaction by generating a large quantity of bubbles and can accelerate the digestion.
Description
Technical field
The present invention relates to the Amlodipine Besylate Tablet preparation, be specifically related to contain the medicine film preparation of Amlodipine Besylate Tablet.
Background technology
Amlodipine Besylate Tablet is nifedipine class calcium antagonists, is used for hypertension and anginal treatment.Its preparation is become the medicine film preparation, need not use water delivery service, be placed on the tongue instantly, can improve patient's compliance, be subject to the patient and welcome; And its production technology is simple, and power consumption is few, and cost is lower.
The medicine film preparation is as far back as i.e. existing many researchs of nineteen seventies, such 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) to membrane as official preparation.
Yet membrane is thin, light, little, the easy moisture absorption, thereby to having relatively high expectations of packing, should be easy to use, should be able to guarantee again the quality of medicine, and domestic present packaged form uses inconvenience, not attractive in appearance; The drug loading of membrane not high (general 30～60mg is following), and to carry out taste masking.These have all restricted development and the application of membrane.
In recent years, the membrane development is swift and violent, and calendar year 2001 Pfizer company has released
With
Product is used for anti-halitosis in advance.Novartis company has also released folk prescription or the compound oral membrane that a series of effective ingredient are diphenhydramine, phenylephrine and dextromethorphan, is used for prevention and the treatment of flu, cough or rhinitis.There is subsequently more pelliculae pro cavo oris product to occur.Biofilm company is used for the pelliculae pro cavo oris technology product of physical strength reinforcing, vitimin supplement, hypersexuality and appetite-suppressing.Ondansetron (ondansetron) membrane and its oral cavity quick disintegrating slice of the exploitation of MonosolRx company
Bioequivalence obtains the approval of FDA in July, 2010.The product of the prevention snoring of the development of PassionforLifeHealthcare company and a kind of uniqueness of having gone on the market
Voglibose (voglibose) membrane of Japan Kyukyu yakuhin Kogyo K.K. development was released in August, 2006, was used for improving the diabetics postprandial hyperglycemia.
Patent about membrane also emerges in an endless stream, and the edible water-soluble film (CN101516331A) that contains foam reducing flavoring agent is arranged, the film bandage (CN101389309A) that is used for 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 of edible film (CN101744791A), the film (CN101346135A) that is used for the adjusted pH that activating agent sends, the film bandage (CN101389309A) that is used for mucosal administration of actives, non-mucoadhesive film dosage forms (CN101626756A), disintegrable oral films (CN101384249A), membrane that can be Orally administered (CN101621990A), be used for neuroleptic, the oral fast that can not be spued collapses film (CN101287445A), instant capacity membrane (CN100396332C) etc.The inventor has also applied for the patent of new packaged form of packaging machine, the membrane of production machine, the membrane of membrane, to promote membrane development at home.
The inventor usually runs into following two problems in the R﹠D process of membrane:
1) active constituents of medicine usually has bitterness, needs taste masking.Adding effervescent is a kind of known comparatively effectively method to modify taste, effervescent is comprised of acidizer (such as citric acid, tartaric acid, fumaric acid, adipic acid and malic acid etc.) and alkaline agent (such as sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate and calcium carbonate etc.), both react after the entry, produce a large amount of carbon dioxide, it can temporarily benumb taste bud and taste masking.But in the process of preparation membrane, normally adjuvant is scattered in the aqueous solvent with active constituents of medicine, repastes the cloth drying and forming-film.Acidizer in the effervescent and alkaline agent react in the with slurry process, can't retain in the film simultaneously.When 2) preparing the compound recipe membrane, because the physicochemical property of the active component in the compound recipe is different, the prescription and the technique that are fit to are different, influence each other sometimes.The compound recipe that for example is comprised of A and B, acidic excipient can strengthen the stability of A material, has but affected the dissolubility of B material, makes B be difficult for being uniformly dispersed in pulping process.
Summary of the invention
The purpose of this invention is to provide the membranaceous preparation of a kind of Amlodipine Besylate Tablet, the defective that exists to overcome prior art satisfies clinical needs.
The membranaceous preparation of described Amlodipine Besylate Tablet comprises the active medicine Amlodipine Besylate Tablet of strip film band and load treatment effective dose thereon;
Described strip film band, comprise acid strip film band and alkaline strip film band, described acid strip film band and alkaline strip film band are connected, and the space arranges, described space arranges and refers to, when being provided with many described acid strip film bands and alkaline strip film band, described acid strip film band and alkaline strip film band space arrange;
Described acid strip film band take the highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20%, preferred 2～10% acidizer, and described acidizer is selected from citric acid, tartaric acid, fumaric acid, maleic acid, adipic acid or malic acid;
Described alkaline strip film band take the highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20%, preferred 2～10% alkaline agent, and described alkaline agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or calcium carbonate;
Described Amlodipine Besylate Tablet loads on the acid strip film band, also can load on the alkaline strip film band, also can load on simultaneously on acid strip film band and the alkaline strip film band;
Preferably, described acid strip film band and alkaline strip film band also comprise in plasticizer, correctives, coloring agent or the stabilizing agent more than one;
Preferably, described acid strip film band comprises the component of following percentage by weight:
Described alkaline strip film band comprises the component of following percentage by weight:
In the gross weight of described membranaceous preparation, the content of described Amlodipine Besylate Tablet is 1～30%, preferred 5～30%;
Described membranaceous preparation thickness is 0.04～0.20mm, preferred 0.06～0.10mm;
The invention still further relates to the membranaceous preparation of Amlodipine Besylate Tablet that another kind is provided with blank tape, the described membranaceous preparation of Amlodipine Besylate Tablet that is provided with blank tape, also comprise blank tape, described blank tape is arranged between described acid strip film band and the alkaline strip film band, and be connected with described acid strip film band and alkaline strip film band respectively, described blank tape comprises the highly-water-soluble macromolecule filming material;
Described Amlodipine Besylate Tablet loads on more than one in acid strip film band, blank tape or the alkaline strip film band;
Preferably, described blank tape also comprises more than one in plasticizer, correctives, coloring agent or the stabilizing agent;
Described water soluble polymer filmogen comprises more than one in polyvinyl alcohol (PVA), hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), sodium alginate, CMC-Na, polyoxyethylene (PEO), Bletilla glucomannan, maltodextrin, corn starch or the carrageenan;
Described acidizer is selected from citric acid, tartaric acid, fumaric acid, maleic acid, adipic acid or malic acid;
Described alkaline agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or calcium carbonate;
Described plasticizer comprises more than one in Polyethylene Glycol (PEG), glycerol or the Tween 80;
Described correctives comprises more than one in sweeting agent, acidic flavoring agent, aromatic, resin macromolecular material, lecithin, cephalin or the phosphatidic acid etc.;
Described stabilizing agent is selected from sodium sulfite, sodium sulfite, EDTA-2Na, BHA, BHT or vitamin E etc.;
Described coloring agent is selected from titanium dioxide, various natural pigment or artificial color etc.;
Preferably:
Described acid strip film band comprises the component of following percentage by weight:
Described alkaline strip film band comprises the component of following percentage by weight:
Described blank tape comprises the component of following percentage by weight:
In the gross weight of described membranaceous preparation, the content of described Amlodipine Besylate Tablet is 1～30%.
The preparation method of the membranaceous preparation of described Amlodipine Besylate Tablet comprises the steps:
(1) Amlodipine Besylate Tablet, acidizer and other adjuvants are mixed with water, the acquisition weight concentration is 15～35% water slip, makes acid serosity A;
(2) Amlodipine Besylate Tablet, alkaline agent and other adjuvants are mixed with water, the acquisition weight concentration is 15～35% water slip, makes alkaline slurry B;
(3) serosity A and serosity B are coated on the flat board at the interval successively, because the solvent expansion effect is complex as a whole, obtain the medicine carrying thin film;
Term " successively interval coating " refers to, and one is serosity A, and other one is serosity B;
(4) the medicine carrying thin film that step (3) is obtained, dry 5～30min obtains described membranaceous preparation under 50～90 ℃ temperature.
Further, comprise the preparation method of the membranaceous preparation of Amlodipine Besylate Tablet of blank tape, comprise the steps:
(1) Amlodipine Besylate Tablet, acidizer and other adjuvants are mixed with water, the acquisition weight concentration is 15～35% water slip, makes acid serosity A;
(2) Amlodipine Besylate Tablet, alkaline agent and other adjuvants are mixed with water, the acquisition weight concentration is 15～35% water slip, makes alkaline slurry B;
(3) Amlodipine Besylate Tablet and other adjuvants are mixed with water, the acquisition weight concentration is 15～35% water slip, makes blank serosity C;
(3) serosity A, serosity B and blank serosity C are coated on the flat board at the interval successively, because the solvent expansion effect is complex as a whole, obtain the medicine carrying thin film;
(4) the medicine carrying thin film that step (3) is obtained, dry 5～30min obtains described compound membranaceous preparation under 50～90 ℃ temperature.
Need to prove, when the content of a certain component is 0, during preparation, namely do not add.
The using method of membranaceous preparation of the present invention is identical with conventional membrane.
The beneficial effect of membranaceous preparation of the present invention is:
The inventor is coated with two or more by a large amount of experiment accumulation simultaneously when coating, finally form more than one compound membrane.Many film can be realized following specific purposes: 1) make the effervescent film: contain the acidizers such as citric acid, tartaric acid in the film, article one, contain the alkaline agents such as sodium carbonate, sodium bicarbonate or calcium carbonate in the film, become the effervescent film after meeting water, produce a large amount of bubbles, benumb olfactory sensation and taste masking, and can accelerate stripping.2) preparation compound recipe film: can study prescription, the technique of heterogeneity respectively, compound when coating, can reduce influencing each other between heterogeneity in the compound recipe, in addition, many film also can be rendered as double-colored or polychrome film, during especially for children preparation, increase the aesthetic feeling of medicine, improve the interest that the child takes medicine.
Description of drawings
Fig. 1 is the membranaceous preparation structure schematic diagram of Amlodipine Besylate Tablet.
Fig. 2 is the membranaceous preparation structure schematic diagram of Amlodipine Besylate Tablet with blank tape.
Fig. 3 is the Amlodipine Besylate Tablet film stripping curve of embodiment 1.
Fig. 4 is the Amlodipine Besylate Tablet film stripping curve of embodiment 2.
Fig. 5 is the Amlodipine Besylate Tablet film stripping curve of embodiment 5.
Fig. 6 is the Amlodipine Besylate Tablet film stripping curve of embodiment 6.
The specific embodiment
Referring to Fig. 1, the membranaceous preparation of described Amlodipine Besylate Tablet comprises acid strip film band 1 and alkaline strip film band 2, and described acid strip film band 1 and alkaline strip film band 2 are connected, and the space arranges.
Referring to Fig. 2, preferably, the membranaceous preparation of described Amlodipine Besylate Tablet also comprises blank tape 3, described blank tape 3 is arranged between described acid strip film band 1 and the alkaline strip film band 2, and is connected with described acid strip film band 1 and alkaline strip film band 2 respectively.
1) gets Amlodipine Besylate Tablet 34.7g adding distil water 700ml, stir, be uniformly dispersed, add successively while stirring again citric acid 20g, stevioside 20g and titanium dioxide 10g, add at last PEO115.3g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get Amlodipine Besylate Tablet 34.7g adding distil water 700ml, stir, be uniformly dispersed, add successively while stirring again calcium carbonate 20g, stevioside 20g and titanium dioxide 10g, add at last PEO115.3g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity B.
Serosity A and serosity B are added in the dosing tank, and this dosing tank is comprised of two parallel sulculuses, and width is 1.2cm, and the spacer width between sulculus is 0.1cm.Start the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 50 ℃ of dry 20min because the solvent expansion effect, 2 serosity are complex as a whole, and obtain the medicine carrying thin film; Adopt again the knurling rolls embossing, according to the assay result, cut into certain size after, peel off from stainless steel band, pack and get final product.Its structure as shown in Figure 1.
The medicine film preparation that obtains, thickness is 0.06mm, can make 2 specifications: every contains amlodipine 2.5mg or 5mg(in amlodipine).Treatment hypertension is grown up each 2.5～5mg 1 time on the 1st; The treatment angina pectoris is grown up 1 time on the 1st, each 5mg.
This medicine film preparation is aesthetic in appearance.Become the effervescent film after meeting water, produce a large amount of bubbles, stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk folder that is 2.0mm with two-layer sieve aperture internal diameter respectively, check according to the method (two appendix X of Chinese Pharmacopoeia version in 2010 A) under the disintegration inspection technique tablet item, observe and the record membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 22 ± 3s.
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X of Chinese Pharmacopoeia version in 2010 C three therapeutic methods of traditional Chinese medicine) device, take water 100ml as dissolution medium, rotating speed is that per minute 50 turns, from test sample contact dissolution medium, immediately timing is respectively in the time of 30 seconds, 1,2,3,5 and 10 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate every stripping quantity according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2010 D).Its In Vitro Dissolution curve is seen Fig. 3.As seen from Figure 3, the In Vitro Dissolution of Amlodipine Besylate Tablet film of the present invention is very fast, dissolve complete during 2min.
1) gets Amlodipine Besylate Tablet 34.7g adding distil water 800ml, stir, be uniformly dispersed, add successively while stirring again PEG40010g, tartaric acid 12.5g, saccharin sodium 10g and erythrosine pigment 0.2g, add at last HPC100g and PVA32.6g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get Amlodipine Besylate Tablet 34.7g adding distil water 800ml, stir, be uniformly dispersed, add successively while stirring again PEG40010g, sodium bicarbonate 12.5g, saccharin sodium 10g and erythrosine pigment 0.2g, add at last HPC100g and HPMC32.6g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity B.
Serosity A and serosity B are added in the dosing tank, and this dosing tank is comprised of two parallel sulculuses, and width is 1.2cm, and the spacer width between sulculus is 0.1cm.Start the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 90 ℃ of dry 5min because the solvent expansion effect, 2 serosity are complex as a whole, and obtain the medicine carrying thin film; Adopt again the knurling rolls embossing, according to the assay result, cut into certain size after, peel off from stainless steel band, pack and get final product.Its structure as shown in Figure 1.
The medicine film preparation that obtains, thickness is 0.07mm, can make 2 specifications: every contains amlodipine 2.5mg or 5mg(in amlodipine).Treatment hypertension is grown up each 2.5～5mg 1 time on the 1st; The treatment angina pectoris is grown up 1 time on the 1st, each 5mg.
This medicine film preparation is aesthetic in appearance.Become the effervescent film after meeting water, produce a large amount of bubbles, stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk folder that is 2.0mm with two-layer sieve aperture internal diameter respectively, check according to the method (two appendix X of Chinese Pharmacopoeia version in 2010 A) under the disintegration inspection technique tablet item, observe and the record membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 26 ± 3s.
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X of Chinese Pharmacopoeia version in 2010 C three therapeutic methods of traditional Chinese medicine) device, take water 100ml as dissolution medium, rotating speed is that per minute 50 turns, from test sample contact dissolution medium, immediately timing is respectively in the time of 30 seconds, 1,2,3,5 and 10 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate every stripping quantity according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2010 D).Its In Vitro Dissolution curve is seen Fig. 4.As seen from Figure 4, the In Vitro Dissolution of Amlodipine Besylate Tablet film of the present invention is very fast, dissolve complete during 2min.
1) gets Amlodipine Besylate Tablet 10g adding distil water 500ml, dispersed with stirring is even, add while stirring again aspartame 30g, vitamin E2 g, glycerol 4g, light blue 0.2g and tartaric acid 4g, add at last PVA100g and corn starch 50g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get Amlodipine Besylate Tablet 60g adding distil water 500ml, dispersed with stirring is even, adds while stirring aspartame 30g, vitamin E2 g, glycerol 4g, light blue 0.2g and potassium bicarbonate 4g again, add at last PVA100g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity B.
Serosity A and serosity B are added in the dosing tank, and this dosing tank is comprised of two parallel sulculuses, and width is 1.2cm, and the spacer width between sulculus is 0.1cm.Start the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 10min because the solvent expansion effect, 2 serosity are complex as a whole, and obtain the medicine carrying thin film; Adopt again the knurling rolls embossing, according to the assay result, cut into certain size after, peel off from stainless steel band, pack and get final product.Its structure as shown in Figure 1.
The medicine film preparation that obtains, thickness is 0.06mm, can make 2 specifications: every contains amlodipine 2.5mg or 5mg(in amlodipine).Treatment hypertension is grown up each 2.5～5mg 1 time on the 1st; The treatment angina pectoris is grown up 1 time on the 1st, each 5mg.
This medicine film preparation is aesthetic in appearance.Become the effervescent film after meeting water, produce a large amount of bubbles, stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk folder that is 2.0mm with two-layer sieve aperture internal diameter respectively, check according to the method (two appendix X of Chinese Pharmacopoeia version in 2010 A) under the disintegration inspection technique tablet item, observe and the record membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 23 ± 3s.
1) get Amlodipine Besylate Tablet 60g adding distil water 500ml, dispersed with stirring is even, adds while stirring cyclamate 30g, vitamin E2 g, titanium dioxide 4g and fumaric acid 4g again, add at last HPMC100g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get Amlodipine Besylate Tablet 10g adding distil water 500ml, dispersed with stirring is even, adds while stirring cyclamate 30g, vitamin E2 g, titanium dioxide 4g and potassium carbonate 4g again, add at last HPMC100g and maltodextrin 50g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity B.
Serosity A and serosity B are added in the dosing tank, and this dosing tank is comprised of two parallel sulculuses, and width is 1.2cm, and the spacer width between sulculus is 0.1cm.Start the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 30min because the solvent expansion effect, 2 serosity are complex as a whole, and obtain the medicine carrying thin film; Adopt again the knurling rolls embossing, according to the assay result, cut into certain size after, peel off from stainless steel band, pack and get final product.Its structure as shown in Figure 1.
The medicine film preparation that obtains, thickness is 0.09mm, can make 2 specifications: every contains amlodipine 2.5mg or 5mg(in amlodipine).Treatment hypertension is grown up each 2.5～5mg 1 time on the 1st; The treatment angina pectoris is grown up 1 time on the 1st, each 5mg.
This medicine film preparation is aesthetic in appearance.Become the effervescent film after meeting water, produce a large amount of bubbles, stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk folder that is 2.0mm with two-layer sieve aperture internal diameter respectively, check according to the method (two appendix X of Chinese Pharmacopoeia version in 2010 A) under the disintegration inspection technique tablet item, observe and the record membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 37 ± 4s.
Embodiment 5
The Amlodipine Besylate Tablet film
1) gets Amlodipine Besylate Tablet 34.7g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again malic acid 20g, sucralose 15g and allured red pigment 0.3g, add at last PVA130g, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get Amlodipine Besylate Tablet 2g, adding distil water 100ml is uniformly dispersed, and adds allured red pigment 0.3g and sunset yellow 0.6g again, adds at last PVA31g, stirs, and crosses 80 mesh sieves, removes insoluble matter, vacuum defoamation.Get serosity B.
3) get Amlodipine Besylate Tablet 34.7g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again sodium bicarbonate 20g, sucralose 15g and allured red pigment 0.3g, add at last PVA130g, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity C.
Serosity A, B and C are added in the dosing tank, and this dosing tank is comprised of three parallel sulculuses, and width is respectively 1.2,0.2,1.2cm, and the spacer width between sulculus is 0.1cm.Start the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 70 ℃ of dry 15min because the solvent expansion effect, 3 serosity are complex as a whole, and obtain the medicine carrying thin film; Adopt again the knurling rolls embossing, according to the assay result, cut into certain size after, peel off from stainless steel band, pack and get final product.Its structure as shown in Figure 2.
The medicine film preparation that obtains, thickness is 0.07mm, can make 2 specifications: every contains amlodipine 2.5mg or 5mg(in amlodipine).Treatment hypertension is grown up each 2.5～5mg 1 time on the 1st; The treatment angina pectoris is grown up 1 time on the 1st, each 5mg.
This film preparation is comprised of trichroism, and is aesthetic in appearance, becomes the effervescent film behind the chance water, produces a large amount of bubbles, and stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk folder that is 2.0mm with two-layer sieve aperture internal diameter respectively, check according to the method (two appendix X of Chinese Pharmacopoeia version in 2010 A) under the disintegration inspection technique tablet item, observe and the record membrane all dissolves and the time by screen cloth.The dissolving time limit of Amlodipine Besylate Tablet film of the present invention is very fast, is 27 ± 3s.
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X of Chinese Pharmacopoeia version in 2010 C three therapeutic methods of traditional Chinese medicine) device, take water 100ml as dissolution medium, rotating speed is that per minute 50 turns, from test sample contact dissolution medium, immediately timing is respectively in the time of 30 seconds, 1,2,3,5 and 10 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate every stripping quantity according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2010 D).Its In Vitro Dissolution curve is seen Fig. 5.As seen from Figure 5, the In Vitro Dissolution of Amlodipine Besylate Tablet film of the present invention is very fast, dissolve complete during 2min.
Embodiment 6
The Amlodipine Besylate Tablet film
1) gets Amlodipine Besylate Tablet 34.7g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again PEG40004g, citric acid 10g, cyclamate 10g and allured red pigment 0.3g, add at last HPC141g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A;
2) get PVA33g adding distil water 100ml, stir, add again allured red pigment 0.1g and sunset yellow 0.2g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity B;
3) get Amlodipine Besylate Tablet 34.7g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again PEG40004g, sodium carbonate 10g, cyclamate 10g and allured red pigment 0.3g, add at last HPC141g, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity C.
Serosity A, B and C are added in the dosing tank, and this dosing tank is comprised of three parallel sulculuses, and width is respectively 1.2,0.2,1.2cm, and the spacer width between sulculus is 0.1cm.Start the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 60 ℃ of dry 30min because the solvent expansion effect, 3 serosity are complex as a whole, and obtain the medicine carrying thin film; Adopt again the knurling rolls embossing, according to the assay result, cut into certain size after, peel off from stainless steel band, pack and get final product.Its structure as shown in Figure 2.
The medicine film preparation that obtains, thickness is 0.08mm, can make 2 specifications: every contains amlodipine 2.5mg or 5mg(in amlodipine).Treatment hypertension is grown up each 2.5～5mg 1 time on the 1st; The treatment angina pectoris is grown up 1 time on the 1st, each 5mg.
This film preparation is comprised of trichroism, and is aesthetic in appearance, becomes the effervescent film behind the chance water, produces a large amount of bubbles, and stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk folder that is 2.0mm with two-layer sieve aperture internal diameter respectively, check according to the method (two appendix X of Chinese Pharmacopoeia version in 2010 A) under the disintegration inspection technique tablet item, observe and the record membrane all dissolves and the time by screen cloth.The dissolving time limit of Amlodipine Besylate Tablet film of the present invention is very fast, is 32 ± 3s.
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X of Chinese Pharmacopoeia version in 2010 C three therapeutic methods of traditional Chinese medicine) device, take water 100ml as dissolution medium, rotating speed is that per minute 50 turns, from test sample contact dissolution medium, immediately timing is respectively in the time of 30 seconds, 1,2,3,5 and 10 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate every stripping quantity according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2010 D).Its In Vitro Dissolution curve is seen Fig. 6.As seen from Figure 6, the In Vitro Dissolution of Amlodipine Besylate Tablet film of the present invention is very fast, dissolve complete during 2min.
Embodiment 7
1) gets Amlodipine Besylate Tablet 40g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again xylitol 13g, aspartame 5g, lemon yellow pigment 0.2g, tartaric acid 20g and vitamin E2 g, add at last HPMC120g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get Amlodipine Besylate Tablet 5g adding distil water 100ml, stir, be uniformly dispersed, add while stirring again acesulfame potassium 5g and lemon yellow pigment 0.03g, add at last HPMC5g and PVP18g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity B.
3) get HPMC70g and sodium alginate 20g adding distil water 300ml, stir, add again calcium carbonate 10g and lemon yellow pigment 0.1g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity C.
Serosity A, B, C are added in the dosing tank, and this dosing tank is comprised of three parallel sulculuses, and width is respectively 1.2cm, 0.2cm and 0.6cm, and the spacer width between sulculus is 0.1cm.Start the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 60 ℃ of dry 20min because the solvent expansion effect, 2 serosity are complex as a whole, and obtain the medicine carrying thin film; Adopt again the knurling rolls embossing, according to the assay result, cut into certain size after, peel off from stainless steel band, pack and get final product.Its structure as shown in Figure 2.
The medicine film preparation that obtains, thickness is 0.07mm, can make 2 specifications: every contains amlodipine 2.5mg or 5mg(in amlodipine).Treatment hypertension is grown up each 2.5～5mg 1 time on the 1st; The treatment angina pectoris is grown up 1 time on the 1st, each 5mg.
This medicine film preparation is aesthetic in appearance.Become the effervescent film after meeting water, produce a large amount of bubbles, stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk folder that is 2.0mm with two-layer sieve aperture internal diameter respectively, check according to the method (two appendix X of Chinese Pharmacopoeia version in 2010 A) under the disintegration inspection technique tablet item, observe and the record membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 26 ± 4s.
Embodiment 8 stability studies
Get the film of embodiment 1 and embodiment 5, carry out high temperature, high humidity and exposure experiments to light, investigate the stability of sample.
Hot test: film is removed packing put in the culture dish, under 60 ℃ of conditions, placed 10 days, in the 5th day and sampling in the 10th day, detect content, related substance and the dissolution of Amlodipine Besylate Tablet in the film.
High wet test: film is removed packing put in the culture dish, placed 10 days under relative humidity 75% condition at 25 ℃, in the 5th day and sampling in the 10th day, detect content, related substance and the dissolution of Amlodipine Besylate Tablet in the film.
Exposure experiments to light: film being removed packing put in the culture dish, is to place 10 days under the condition of 4500Lx ± 500Lx in illumination, in the 5th day and sampling in the 10th day, and content, related substance and the dissolution of Amlodipine Besylate Tablet in the detection film.
Testing result sees Table 1～table 2.
Table 1 embodiment 1 stability sample quality inspection result
Hot test (60 ℃) sample quality assay
High wet test (25 ℃, 75%RH) sample quality assay
Exposure experiments to light (4500Lx) sample quality assay
As shown in Table 1, the Amlodipine Besylate Tablet film of this prescription and technique preparation is all stable under high temperature, high humidity and illumination condition.
Table 2 embodiment 5 stability sample quality inspection results
Hot test (60 ℃) sample quality assay
High wet test (25 ℃, 75%RH) sample quality assay
Exposure experiments to light (4500Lx) sample quality assay
As shown in Table 2, the Amlodipine Besylate Tablet film of this prescription and technique preparation is all stable under high temperature, high humidity and illumination condition.
Claims (11)
1. the membranaceous preparation of Amlodipine Besylate Tablet is characterized in that, comprises the active medicine Amlodipine Besylate Tablet of strip film band and load treatment effective dose thereon;
Described strip film band comprises acid strip film band and alkaline strip film band, and described acid strip film band and alkaline strip film band are connected, and the space arranges;
Described acid strip film band take the highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20% acidizer;
Described alkaline strip film band take the highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20% alkaline agent.
2. the membranaceous preparation of Amlodipine Besylate Tablet according to claim 1 is characterized in that, described acid strip film band and alkaline strip film band also comprise in plasticizer, correctives, coloring agent or the stabilizing agent more than one.
3. the membranaceous preparation of Amlodipine Besylate Tablet according to claim 1, it is characterized in that, described acidizer is selected from citric acid, tartaric acid, fumaric acid, maleic acid, adipic acid or malic acid, and described alkaline agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or calcium carbonate.
4. the membranaceous preparation of Amlodipine Besylate Tablet according to claim 1 is characterized in that, described Amlodipine Besylate Tablet loads on the acid strip film band, or loads on the alkaline strip film band, or loads on simultaneously on acid strip film band and the alkaline strip film band.
5. the membranaceous preparation of Amlodipine Besylate Tablet according to claim 1 is characterized in that, described acid strip film band comprises the component of following percentage by weight:
Described alkaline strip film band comprises the component of following percentage by weight:
In the gross weight of described membranaceous preparation, the content of described Amlodipine Besylate Tablet is 1～30%.
6. the membranaceous preparation of Amlodipine Besylate Tablet according to claim 1 is characterized in that, described acid strip film band comprises the component of following percentage by weight:
Described alkaline strip film band comprises the component of following percentage by weight:
In the gross weight of described membranaceous preparation, the content of described Amlodipine Besylate Tablet is 5～30%.
7. the membranaceous preparation of Amlodipine Besylate Tablet is characterized in that, comprises the active medicine Amlodipine Besylate Tablet of strip film band and load treatment effective dose thereon;
Described strip film band comprises acid strip film band, blank tape and alkaline strip film band, and described blank tape is connected with described acid strip film band and alkaline strip film band respectively;
Described acid strip film band take the highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20% acidizer;
Described alkaline strip film band take the highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20% alkaline agent, and described blank tape comprises the highly-water-soluble macromolecule filming material.
8. the membranaceous preparation of Amlodipine Besylate Tablet according to claim 7 is characterized in that, described Amlodipine Besylate Tablet loads on more than one in acid strip film band, blank tape or the alkaline strip film band.
9. the membranaceous preparation of Amlodipine Besylate Tablet according to claim 7 is characterized in that, described acid strip film band, blank tape and alkaline strip film band also comprise more than one in plasticizer, correctives, coloring agent or the stabilizing agent.
10. the membranaceous preparation of Amlodipine Besylate Tablet according to claim 7 is characterized in that, described acid strip film band comprises the component of following percentage by weight:
Described alkaline strip film band comprises the component of following percentage by weight:
Described blank tape comprises the component of following percentage by weight:
In the gross weight of described membranaceous preparation, the content of described Amlodipine Besylate Tablet is 1～30%.
11. the membranaceous preparation of each described Amlodipine Besylate Tablet according to claim 1～10, it is characterized in that, described water soluble polymer filmogen comprises more than one in polyvinyl alcohol (PVA), hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), sodium alginate, CMC-Na, polyoxyethylene (PEO), Bletilla glucomannan, maltodextrin, corn starch or the carrageenan.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310272024.8A CN103356512B (en) | 2013-02-21 | 2013-07-02 | Benzenesulfonic acid amlodipine membranaceous preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201310056459 CN103127035A (en) | 2013-02-21 | 2013-02-21 | Amlodipine besylate membrane preparation |
| CN201310056459.9 | 2013-02-21 | ||
| CN201310272024.8A CN103356512B (en) | 2013-02-21 | 2013-07-02 | Benzenesulfonic acid amlodipine membranaceous preparation |
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| CN103356512B CN103356512B (en) | 2014-12-24 |
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| CN 201310056459 Pending CN103127035A (en) | 2013-02-21 | 2013-02-21 | Amlodipine besylate membrane preparation |
| CN201310272024.8A Active CN103356512B (en) | 2013-02-21 | 2013-07-02 | Benzenesulfonic acid amlodipine membranaceous preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074456A (en) * | 2016-06-30 | 2016-11-09 | 合肥华方医药科技有限公司 | A kind of Amlodipine Besylate Tablet oral instant membrane and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1658835A (en) * | 2002-06-04 | 2005-08-24 | Lts罗曼治疗方法有限公司 | Film-shaped, dissolvable preparations for active substance release and method for the production thereof |
| CN1827170A (en) * | 2005-03-02 | 2006-09-06 | 北京华安佛医药研究中心有限公司 | Composition containing dihydropyridin type of calcium antagonists and fibrates medicine |
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2013
- 2013-02-21 CN CN 201310056459 patent/CN103127035A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1658835A (en) * | 2002-06-04 | 2005-08-24 | Lts罗曼治疗方法有限公司 | Film-shaped, dissolvable preparations for active substance release and method for the production thereof |
| CN1827170A (en) * | 2005-03-02 | 2006-09-06 | 北京华安佛医药研究中心有限公司 | Composition containing dihydropyridin type of calcium antagonists and fibrates medicine |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074456A (en) * | 2016-06-30 | 2016-11-09 | 合肥华方医药科技有限公司 | A kind of Amlodipine Besylate Tablet oral instant membrane and preparation method thereof |
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| CN103356512B (en) | 2014-12-24 |
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