CN103083284B - Film preparation and its preparation method - Google Patents
Film preparation and its preparation method Download PDFInfo
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- CN103083284B CN103083284B CN201310046861.9A CN201310046861A CN103083284B CN 103083284 B CN103083284 B CN 103083284B CN 201310046861 A CN201310046861 A CN 201310046861A CN 103083284 B CN103083284 B CN 103083284B
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- acid
- alkaline
- film band
- medicine
- preparation
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- 238000002360 preparation method Methods 0.000 title claims abstract description 58
- 239000003814 drug Substances 0.000 claims abstract description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 18
- 239000000463 material Substances 0.000 claims abstract description 15
- 230000002378 acidificating effect Effects 0.000 claims abstract description 7
- 239000010408 film Substances 0.000 claims description 107
- 239000002253 acid Substances 0.000 claims description 23
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 21
- 239000010409 thin film Substances 0.000 claims description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 14
- 239000000470 constituent Substances 0.000 claims description 14
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 12
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
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- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 claims description 7
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
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- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 3
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- PLXMOAALOJOTIY-FPTXNFDTSA-N Aesculin Natural products OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)[C@H]1Oc2cc3C=CC(=O)Oc3cc2O PLXMOAALOJOTIY-FPTXNFDTSA-N 0.000 description 1
- 241001313855 Bletilla Species 0.000 description 1
- 206010006326 Breath odour Diseases 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
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- 108010028554 LDL Cholesterol Proteins 0.000 description 1
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- 239000000006 Nitroglycerin Substances 0.000 description 1
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- 230000003213 activating effect Effects 0.000 description 1
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- 239000003433 contraceptive agent Substances 0.000 description 1
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- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a film preparation and its preparation method. The film preparation comprises a strip-shaped film tape and an effective amount of an active medicine loaded thereon. The strip-shaped film tape comprises an acidic strip-shaped film tape and an alkaline strip-shaped film tape, and the acidic strip-shaped film tape and the alkaline strip-shaped film tape are connected into one and are arranged in an interval mode; the acidic strip-shaped film tape is based on a high-water-solubility polymer film forming material, and contains 1-20% of an acidic agent; and the alkaline strip-shaped film tape is based on the high-water-solubility polymer film forming material, and contains 1-20% of an alkaline agent. The film preparation becomes an effervescent film after meeting water and generates a large amount of bubbles to palsy olfaction in order to cover a smell, and the dissolve-out of the film preparation can be accelerated, so the mutual influence among different components in film preparation can be reduced; and furtherly, a plurality of films can be double-color or multicolor films, so the medicine beauty feeling is increased when the films are especially used in children's preparations, and the medicine taking interest of children is improved.
Description
Technical field
The present invention relates to a kind of medicine film preparation and preparation method thereof.
Background technology
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.
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 current packaged form is used 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, membrane development is swift and violent, and calendar year 2001 Pfizer company has released
with
product, 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, for catching a cold, prevention and the treatment of cough or rhinitis.There is subsequently more pelliculae pro cavo oris product to occur.Biofilm company is the product for physical strength reinforcing, vitimin supplement, hypersexuality and appetite-suppressing by pelliculae pro cavo oris technology.Ondansetron (ondansetron) membrane and its oral cavity quick disintegrating slice (Zofran of the exploitation of MonosolRx company
) bioequivalence, in July, 2010, obtain the approval of FDA.Passion for Life Healthcare company develops and the product of the prevention snoring of a kind of uniqueness of having gone on the market
voglibose (voglibose) membrane of Japan Kyukyu yakuhin Kogyo K.K. development, releases in August, 2006, for improving diabetics postprandial hyperglycemia.
Patent about membrane also emerges in an endless stream, there is the edible water-soluble film (CN101516331A) that contains foam reducing flavoring agent, film bandage (CN101389309A) 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) of the adjusted pH sending for activating agent, film bandage (CN101389309A) for mucosal administration of actives, non-mucoadhesive film dosage forms (CN101626756A), disintegrable oral films (CN101384249A), membrane that can be Orally administered (CN101621990A), 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 production machine of membrane, the patent of the new packaged form of the packaging machine of membrane, membrane, to promote membrane development at home.
The inventor, in the R&D process of membrane, usually runs into following two problems:
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 (as citric acid, tartaric acid, fumaric acid, adipic acid and malic acid etc.) and alkaline agent (as sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate and calcium carbonate etc.), after entering water, both react, produce a large amount of carbon dioxide, it can temporarily benumb taste bud and taste masking.But in preparing the process of membrane, normally adjuvant is scattered in aqueous solvent together with active constituents of medicine, repastes cloth drying and forming-film.Acidizer in effervescent and alkaline agent react in process with slurry, cannot retain in film simultaneously.2), while preparing compound recipe membrane, because the physicochemical property of the active component in compound recipe is different, applicable prescription and technique are different, influence each other sometimes.The compound recipe being for example comprised of A and B, acidic excipient can strengthen the stability of A material, has but affected the dissolubility of B material, makes B in pulping process, be difficult for being uniformly dispersed.
Summary of the invention
One of the object of the invention is to be to provide a kind of membranaceous preparation and preparation method thereof, the defect existing to overcome prior art, meets clinical needs.
Two of object of the present invention is to provide a kind of strip film band for medicine carrying, for the preparation of membranaceous preparation.
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 space arranges;
Described acid strip film band, take highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20%, preferably 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 highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20%, preferably 2～10% alkaline agent, and described alkaline agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or calcium carbonate;
Preferably, described acid strip film band and alkaline strip film band, also comprise plasticizer and correctives;
Preferably, described acid strip film band and alkaline strip film band also comprise coloring agent and stabilizing agent;
Preferably, described acid strip film band comprises the component of following percentage by weight:
Highly-water-soluble macromolecule filming material 40～98%, preferably 65～85%;
Acidizer 1～20%, preferably 2～10%;
Plasticizer 0～20%, preferably 0～5%;
Correctives 0～30%, preferably 5～15%;
Coloring agent 0～5%, preferably 0.1～5%;
Stabilizing agent 0～5%, preferably 0～1%;
Described alkaline strip film band comprises the component of following percentage by weight:
Highly-water-soluble macromolecule filming material 40～98%, preferably 65～85%;
Alkaline agent 1～20%, preferably 2～10%;
Plasticizer 0～20%, preferably 0～5%;
Correctives 0～30%, preferably 5～15%; ;
Coloring agent 0～5%, preferably 0.1～5%;
Stabilizing agent 0～5%, preferably 0～1%.
A membranaceous preparation, comprises described strip film band and loads on more than one the active medicine for the treatment of effective dose in its acid strip film or alkaline strip film band;
That is, active medicine can load on acid strip film band, also can load on alkaline strip film band, also can load on acid strip film band and alkaline strip film band simultaneously;
Preferably, described acid strip film band comprises the component of following percentage by weight:
Active constituents of medicine 0～30%, preferably 5～30%;
Highly-water-soluble macromolecule filming material 40～98%, preferably 50～75%;
Acidizer 1～20%, preferably 2～10%;
Plasticizer 0～20%, preferably 0～5%;
Correctives 0～30%, preferably 5～15%;
Coloring agent 0～5%, preferably 0.1～5%;
Stabilizing agent 0～5%, preferably 0～1%;
Described alkaline strip film band comprises the component of following percentage by weight:
Active constituents of medicine 0～30%, preferably 5～30%;
Highly-water-soluble macromolecule filming material 40～98%, preferably 50～75%;
Alkaline agent 1～20%, preferably 2～10%;
Plasticizer 0～20%, preferably 0～5%;
Correctives 0～30%, preferably 5～15%;
Coloring agent 0～5%, preferably 0.1～5%;
Stabilizing agent 0～5%, preferably 0～1%;
In the gross weight of described membranaceous preparation, the content of described active constituents of medicine is 1～30%, preferably 5～30%;
Described membranaceous preparation thickness is 0.04～0.20mm, preferably 0.06～0.10mm;
Described active constituents of medicine, so long as in water, ethanol and acetone kind solvent solubilized or dispersible, all can load in described thin film, include, but are not limited to the medicine of donepezil, Zolmitriptan, loperamide, simvastatin, olanzapine, diphenhydramine, cetirizine hydrochloride, scopolamine hydrobromide, chlorphenamine maleate, voglibose, Lizakuputan benzoate, Zolpidemtar Trate, Ondansetron Hydrochloride, asenapine, escitalopram oxalate, vaccine or polypeptide etc.;
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 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 Tween 80;
Described correctives comprises more than one in sweeting agent, acidic flavoring agent, aromatic, resin macromolecular material, lecithin, cephalin or 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.;
The preparation method of described membranaceous preparation, comprises the steps:
(1) active constituents of medicine, acidizer and other adjuvants are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes acid serosity A;
(2) active component, alkaline agent and other adjuvants are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes alkaline slurry B;
(3) serosity A and serosity B are coated in to flat board above in interval successively, due to solvent expansion effect, are complex as a whole, obtain medicine carrying thin film;
Term " interval coating successively ", refers to, and one is serosity A, and other one is serosity B;
(4) medicine carrying thin film step (3) being obtained, at the temperature of 50～90 ℃, dry 5～30min, obtains described membranaceous preparation.
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 accumulates by a large amount of experiments, when coating, is coated with two or more simultaneously, finally forms more than one compound membrane.Many film can be realized following specific purposes: 1) make effervescent film: in a film, contain the acidizers such as citric acid, tartaric acid, article one, in film, contain the alkaline agents such as sodium carbonate, sodium bicarbonate or calcium carbonate, after meeting water, become effervescent film, produce a large amount of bubbles, benumb olfactory sensation and taste masking, and can accelerate stripping.2) prepare compound recipe film: can to the prescription of heterogeneity, technique, study respectively, compound when coating, can reduce influencing each other between heterogeneity in 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 child takes medicine.
Accompanying drawing explanation
Fig. 1 is membranaceous preparation structure schematic diagram.
Fig. 2 is simvastatin film stripping curve.
Fig. 3 is loperamide film stripping curve.
Fig. 4 is donepezil film stripping curve.
Fig. 5 is Zolmitriptan film stripping curve.
Fig. 6 is escitalopram oxalate film stripping curve.
The specific embodiment
Referring to Fig. 1, described membranaceous preparation, 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 space arranges.
Embodiment 1
1) get distilled water 700ml, add while stirring PEG40010g, citric acid 10g, cyclamate 10g and erythrosine pigment 0.25g, finally add HPC100g and maltodextrin 70g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get distilled water 700ml, add while stirring PEG40010g, sodium carbonate 10g, cyclamate 10g and allured red pigment 0.25g, finally add HPC100g and maltodextrin 70g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
Serosity A and serosity B are added in 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 coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 10min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, cut into after certain size, from stainless steel band, peel off, pack and get final product.This film preparation is Double-color film, novelty aesthetic in appearance.After meeting water, become effervescent film, produce a large amount of bubbles, stripping is rapid.
Embodiment 2
Simvastatin film
1) get simvastatin 40g adding distil water 600ml, stir, be uniformly dispersed, then add while stirring sucralose 18g, light blue 0.2g, calcium carbonate 20g and vitamin E2 g, finally add PEO120g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get PEO80g adding distil water 300ml, stir, then add citric acid 20g and light blue 0.1g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
Serosity A and serosity B are added in dosing tank, and this dosing tank is comprised of two parallel sulculuses, and width is respectively 1.2cm and 0.6cm, and the spacer width between sulculus is 0.1cm.Start coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 60 ℃ of dry 20min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, according to assay result, cut into after certain size, from stainless steel band, peel off, pack and get final product.
Many medicine film preparations that obtain, thickness is 0.08mm, every containing simvastatin 5mg.For hypercholesterolemia and coronary heart disease treatment.Hypercholesterolemiapatients patients is general to be begun to take dosage is 10mg every day, night decoction being taken at a draught.For the patient of the mild to moderate rising of cholesterol levels, beginning to take dosage is 5mg every day.More than if need to adjust, dosage answers interval surrounding, maximal dose is 40mg every day, night decoction being taken at a draught.When low-density lipoprotein cholesterol level is down to 75mg/dL(1.94mmol/L) or total cholesterol level be down to 140mg/dL(3.6mmol/L) when following, should lower taking dose.Patients with coronary heart disease can be taken 20mg every night as initial dose.
This medicine film preparation is aesthetic in appearance.After meeting water, become effervescent film, 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 that is 2.0mm with two-layer sieve aperture internal diameter respectively folder, according to the method (two appendix X A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, check, observe and record that membrane all dissolves and by the time of screen cloth.It is very fast that this product is dissolved the time limit, is 41 ± 3s.
Get 6 of this product, with paperclip, clamp respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take water 100ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure and calculate the stripping quantity of every.Stripping curve is shown in accompanying drawing 2.
From accompanying drawing 2, this product In Vitro Dissolution is very fast, in 3min, dissolves completely.
Embodiment 3
Loperamide film
1) get loperamide 10g adding distil water 500ml, dispersed with stirring is even, then adds while stirring aspartame 20g, erythrosine 0.2g, BHT0.2g and maleic acid 20g, finally adds PVA150g, stirs, and crosses 80 mesh sieves, removes insoluble matter, vacuum defoamation.Obtain serosity A.
2) get loperamide 10g adding distil water 500ml, dispersed with stirring is even, then adds while stirring aspartame 20g, erythrosine 0.2g, BHT0.2g and sodium carbonate 20g, finally add PVA50g, sodium alginate 50g and CMC-Na50g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
Serosity A and serosity B are added in 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 coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 60 ℃ of dry 10min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, according to assay result, cut into after certain size, from stainless steel band, peel off, pack and get final product.
The medicine film preparation obtaining, thickness is 0.06mm, every containing loperamide 1mg.Can be used for various acute and chronic diarrhoea.To ileostomy patient, can be used to increase the thick hardness of stool, reduce number of times and the quantity of defecation.Adult takes 2 times every day, each 1.
This medicine film preparation is aesthetic in appearance.After meeting water, become effervescent film, 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 that is 2.0mm with two-layer sieve aperture internal diameter respectively folder, according to the method (two appendix X A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, check, observe and record that membrane all dissolves and by the time of screen cloth.It is very fast that this product is dissolved the time limit, is 35 ± 3s.
Get 6 of this product, with paperclip, clamp respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take water 100ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 0.5,1,2,3,5 and 10 minute, get solution 1ml, filter, get subsequent filtrate, according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure and calculate the stripping quantity of every.Stripping curve is shown in accompanying drawing 3.
From accompanying drawing 3, this product In Vitro Dissolution is very fast, in 2min, dissolves completely.
Embodiment 4
Donepezil film
1) get donepezil 30g adding distil water 700ml, dispersed with stirring is even, then adds while stirring sucralose 30g, PEG40010g, the red 0.2g of temptation and malic acid 20g, finally add PVP50g and HPMC60g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get donepezil 30g adding distil water 700ml, dispersed with stirring is even, add while stirring again sucralose 30g, PEG40010g, the red 0.2g of temptation and sodium bicarbonate 20g, finally add PVP50g and HPMC60g, be stirred into full-bodied solution, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
Serosity A and serosity B are added in 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 coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 10min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, according to assay result, cut into after certain size, from stainless steel band, peel off, pack and get final product.
The medicine film preparation obtaining, thickness is 0.07mm, can make 2 specifications: every 3mg or 5mg.Treatment for slight or moderate dementia of the Alzheimer type symptom.The each 3mg of initial content, once a day, takes before sleeping; And predose was maintained after 1 ~ 2 week, according to therapeutic effect, increase dosage to each 5mg, still once a day.
This medicine film preparation is aesthetic in appearance.After meeting water, become effervescent film, 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 that is 2.0mm with two-layer sieve aperture internal diameter respectively folder, according to the method (two appendix X A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, check, observe and record that membrane all dissolves and by the time of screen cloth.It is very fast that this product is dissolved the time limit, is 43 ± 4s.
Get 6 of this product, with paperclip, clamp respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take water 100ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure and calculate the stripping quantity of every.Stripping curve is shown in accompanying drawing 4.
From accompanying drawing 4, this product In Vitro Dissolution is very fast, in 3min, dissolves completely.
Embodiment 5
Zolmitriptan film
1) get Zolmitriptan 24g adding distil water 600ml, dispersed with stirring is even, add while stirring again aspartame 4g, acesulfame potassium 4g, saccharin sodium 2g, glycerol 8g, titanium dioxide 10g and tartaric acid 4g, finally add maltodextrin 54g and HPC90g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get Zolmitriptan 24g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again aspartame 4g, acesulfame potassium 4g, saccharin sodium 2g, glycerol 8g, titanium dioxide 10g and potassium carbonate 4g, finally add maltodextrin 54g and HPC90g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
Serosity A, B are added in 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 coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 10min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, according to assay result, cut into after certain size, from stainless steel band, peel off, pack and get final product.
The compound herbal membrane preparation obtaining, thickness is 0.07mm, every containing Zolmitriptan 2.5mg.Be applicable to with/without the migrainous acute treatment of tendency.Once take a slice.If symptom continue need medication for the first time after 2 hours secondary take medicine, or recurrence, takes medicine still effective again, in 24 hours, maximal dose must not surpass 15mg.
This medicine film preparation is aesthetic in appearance.After meeting water, become effervescent film, 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 that is 2.0mm with two-layer sieve aperture internal diameter respectively folder, according to the method (two appendix X A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, check, observe and record that membrane all dissolves and by the time of screen cloth.It is very fast that this product is dissolved the time limit, is 41 ± 4s.
Get 6 of this product, with paperclip, clamp respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take water 100ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure and calculate the stripping quantity of every.Stripping curve is shown in accompanying drawing 5.From accompanying drawing 5, this product In Vitro Dissolution is very fast, in 3min, dissolves completely.
Embodiment 6
Escitalopram oxalate film
1) get escitalopram oxalate 60g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again xylitol 10g, stevioside 20g, light blue 0.2g and fumaric acid 10g, finally add corn starch 80g and HPC20g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get escitalopram oxalate 60g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again xylitol 10g, stevioside 20g, light blue 0.2g and potassium bicarbonate 10g, finally add corn starch 80g and sodium alginate 20g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
Serosity A, B are added in 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 coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 10min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, according to assay result, cut into after certain size, from stainless steel band, peel off, pack and get final product.
The compound herbal membrane preparation obtaining, thickness is 0.08mm, every containing escitalopram 5mg.Be used for the treatment of depression.Every day 1 time, each 2.
This medicine film preparation is aesthetic in appearance.After meeting water, become effervescent film, 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 that is 2.0mm with two-layer sieve aperture internal diameter respectively folder, according to the method (two appendix X A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, check, observe and record that membrane all dissolves and by the time of screen cloth.It is very fast that this product is dissolved the time limit, is 45 ± 3s.
Get 6 of this product, with paperclip, clamp respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take water 100ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure and calculate the stripping quantity of every.Stripping curve is shown in accompanying drawing 6.From accompanying drawing 6, this product In Vitro Dissolution is very fast, in 3min, dissolves completely.
Claims (8)
1. membranaceous preparation, is characterized in that, comprises acid strip film band and alkaline strip film band, and described acid strip film band and alkaline strip film band are connected, and space arranges;
Described acid strip film band, take highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20% acidizer; Described alkaline strip film band, take highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20% alkaline agent;
The preparation method of described membranaceous preparation, comprises the steps:
(1) active constituents of medicine, acidizer and other adjuvants are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes acid serosity A;
(2) active constituents of medicine, alkaline agent and other adjuvants are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes alkaline slurry B;
(3) serosity A and serosity B are coated in to flat board above in interval successively, due to solvent expansion effect, are complex as a whole, obtain medicine carrying thin film;
(4) medicine carrying thin film step (3) being obtained, at the temperature of 50～90 ℃, dry 5～30min, obtains described membranaceous preparation;
Active constituents of medicine loads on acid strip film band, or loads on alkaline strip film band, or loads on acid strip film band and alkaline strip film band simultaneously.
2. membranaceous preparation 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.
3. membranaceous preparation according to claim 1, is characterized in that, described acid strip film band and alkaline strip film band also comprise more than one in plasticizer, correctives, coloring agent or stabilizing agent.
4. membranaceous preparation according to claim 3, 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 active constituents of medicine is 1～30%.
5. membranaceous preparation according to claim 3, 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 active constituents of medicine is 5～30%.
6. according to the membranaceous preparation described in claim 1～5 any one, it is characterized in that, described active constituents of medicine is the medicine of donepezil, Zolmitriptan, loperamide, simvastatin, olanzapine, diphenhydramine, cetirizine hydrochloride, scopolamine hydrobromide, chlorphenamine maleate, voglibose, Lizakuputan benzoate, Zolpidemtar Trate, Ondansetron Hydrochloride, asenapine, escitalopram oxalate, vaccine or polypeptide.
7. membranaceous preparation according to claim 5, it is characterized in that, described highly-water-soluble macromolecule filming material is selected from more than one in polyvinyl alcohol, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, sodium alginate, CMC-Na, polyoxyethylene, Rhizoma Bletillae gel, maltodextrin, corn starch or carrageenan;
Described plasticizer is selected from more than one in Polyethylene Glycol, glycerol or Tween 80;
Described correctives is selected from more than one in sweeting agent, acidic flavoring agent, aromatic, resin macromolecular material, lecithin, cephalin or phosphatidic acid;
Described stabilizing agent is selected from sodium sulfite, sodium sulfite, EDTA-2Na, BHA, BHT or vitamin E;
Described coloring agent is selected from titanium dioxide, various natural pigment or artificial color.
8. according to the preparation method of the membranaceous preparation described in claim 1～7 any one, it is characterized in that, comprise the steps:
(1) active constituents of medicine, acidizer and other adjuvants are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes acid serosity A;
(2) active component, alkaline agent and other adjuvants are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes alkaline slurry B;
(3) serosity A and serosity B are coated in to flat board above in interval successively, due to solvent expansion effect, are complex as a whole, obtain medicine carrying thin film;
(4) medicine carrying thin film step (3) being obtained, at the temperature of 50～90 ℃, dry 5～30min, obtains described membranaceous preparation.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12138353B2 (en) | 2016-12-20 | 2024-11-12 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
| US12329862B2 (en) | 2018-06-20 | 2025-06-17 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2995301B1 (en) * | 2013-05-10 | 2019-08-07 | CTC Bio, Inc. | Film preparation containing donepezil-free base and method for producing same |
| TR201509009A1 (en) * | 2014-12-11 | 2017-02-21 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A thin film strip of asenapine |
| CN104586819A (en) * | 2015-01-05 | 2015-05-06 | 万特制药(海南)有限公司 | Medicine composition for treating senile dementia and preparation method thereof |
| EP3558276B1 (en) | 2016-12-20 | 2024-11-06 | LTS Lohmann Therapie-Systeme AG | Transdermal therapeutic system containing asenapine and polysiloxane or polyisobutylene |
| CN110799180A (en) | 2017-06-26 | 2020-02-14 | 罗曼治疗系统股份公司 | Transdermal therapeutic system containing asenapine and siloxane acrylic hybrid polymer |
| BR112020026099A2 (en) | 2018-06-20 | 2021-03-23 | Lts Lohmann Therapie-Systeme Ag | transdermal therapeutic system containing asenapine |
| CN110251489B (en) * | 2019-07-02 | 2022-05-20 | 沈阳药科大学 | Olanzapine oral instant film agent and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12138353B2 (en) | 2016-12-20 | 2024-11-12 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
| US12329862B2 (en) | 2018-06-20 | 2025-06-17 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
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