CN101084884B - Oral film composition capable of masking pharmaceutical unpleasant flavor and preparation method thereof - Google Patents
Oral film composition capable of masking pharmaceutical unpleasant flavor and preparation method thereof Download PDFInfo
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- CN101084884B CN101084884B CN2007101181038A CN200710118103A CN101084884B CN 101084884 B CN101084884 B CN 101084884B CN 2007101181038 A CN2007101181038 A CN 2007101181038A CN 200710118103 A CN200710118103 A CN 200710118103A CN 101084884 B CN101084884 B CN 101084884B
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Abstract
The invention relates to a film composition capable of covering unpleasant odor of active medicament for oral administration and its preparation method. In the composition, the ratio of active medicament and medicinal water insoluble material is 1:1-10, and the ratio of medicinal water insoluble material and medicinal water-soluble polymer material is 1:0.5-50. The preparation method is shown in specification. Medicament is imbeded in water-insoluble material, while correctant is mixed in water-soluble polymer material, thereby preparing film with good taste and easy deglutition for oral administration.
Description
Technical field
The present invention relates to a kind of oral film compositions and preparation method thereof, specifically relate to oral film compositions of a kind of bad smell of covering active medicine and preparation method thereof.
Background technology
Oral administration is the most frequently used administering mode, and type of preparation is also a lot, but exists variety of issue for different users.Conventional oral solid formulation as coated tablet, capsule, can cover the adverse drug abnormal smells from the patient, but the patient of child, old man and some dysphagias is difficult for taking.Other preparations, as: dispersible tablet, oral cavity disintegration tablet, chewable tablet, granule, oral liquid, powder, dry suspension etc., though be easy to take, and,, also can improve taste by adding correctives for the lighter medicine of disagreeable taste; But,, can not improve the bad sensation when oral even add a large amount of correctivess for the heavier medicine of disagreeable taste.
The advantage of membrane is that technology is simple, does not have powder to fly upward, and the moulding material consumption is few, and content is accurate, good stability, compatibility is with low uncertainty, analyzes to disturb and lacks, absorb rapid-action, but at present in the prior art, water miscible film material of the general independent selection of oral film preparation or the preparation of water-insoluble film material.The water-solubility membrane material can dissolve in the oral cavity, and is easy-to-swallow, but for the more serious chemical compound of bad mouthfeel, even add a large amount of correctivess, can not improve the bad sensation when oral.As select for use water-insoluble film material to prepare membrane, and insoluble in the oral cavity because of the membrane of preparation, can avoid the stripping of bad mouthfeel chemical compound, but swallowing of monoblock membrane is very difficult, for the patient of child and dysphagia, difficulty is particularly serious.
Therefore, still need further oral membrane to be carried out the research of prescription and preparation method up to now, good to produce mouthfeel, easy-to-swallow oral membrane satisfies patient's needs.
Summary of the invention
An object of the present invention is to provide a kind of oral film compositions of covering the active medicine bad smell.Another object of the present invention provides a kind of method for preparing above-mentioned oral membrane, makes the membrane mouthfeel of preparation good, easy-to-swallow, solves problems of the prior art.
One aspect of the present invention provides a kind of oral membrane of covering the active medicine bad smell, wherein active medicine and medicinal water-insoluble macromolecular material and/or solid-state organic ester, solid-state organic alcohol, solid-state organic acid ratio are 1: 1-10, medicinal water-insoluble macromolecular material and/or solid-state organic ester, solid-state organic alcohol, solid-state organic acid and the ratio of medicinal soluble macromolecular material are 1: 0.5-50.
Oral membrane of the present invention can also contain correctives, and pharmaceutical pack is embedded in the pharmaceutically useful water-insoluble material, and correctives is blended in the pharmaceutically useful water-soluble material.After oral, water-soluble material discharges correctives at Orally dissolving, makes membrane softening simultaneously, is broken into fritter; The medical compounds of indissoluble is embedded in the water-insoluble material, and is little to the mouthfeel influence; Behind mixing in water for oral taking, film preparation discharges chemical compound in vivo.Integral body feels it is that mouthfeel is good, easy-to-swallow.
Can be used for medicine of the present invention and comprise following various kinds of drug: antibiotic, antiviral agents, analgesic, anesthetics, antihistaminic, anti-arthritic, antasthmatic, antidepressants, antidiabetic drug, diarrhea medicine, anti-inflammatory agent, antinanseant, antineoplastic agent, antiparkinsonian drug, antipyretic, psychosis, H2 antagonist, cardiovascular drug, antihypertensive, vasodilator, ACE inhibitor.
In general, above-described various kinds of drug all has bitterness or unpleasant taste is arranged.This specific class medicine comprises racecadotril, Roxithromycin, the amoxicillin, azithromycin, cefaclor, acetaminophen, ibuprofen, nimesulide, guaifenesin, caffeine, voglibose, Mitiglinide, Entecavir, Navoban (Soz), loratadine, desloratadine, fluoxetine, Sertraline, citalopram, Zaleplon, sldenafil, Zolmitriptan, meloxicam, breviscapine, memantine, finasteride, lansoprazole, tamoxifen, voriconazole, valsartan, simvastatin, lovastatin, Pitavastatin, atorvastatin, nifedipine, amlodipine, TANSHINONES, bilobalide, ginkgetin, Yixintong.Especially oral effective dose is lower than 20mg/ time medicine, employing the present invention preferably is prepared into oral membrane, for example: racecadotril, caffeine, voglibose, Mitiglinide, Entecavir, Navoban (Soz), loratadine, desloratadine, fluoxetine, Sertraline, citalopram, Zaleplon, sldenafil, Zolmitriptan, meloxicam, breviscapine, memantine, Pitavastatin, atorvastatin, nifedipine, amlodipine, TANSHINONES, bilobalide, ginkgetin.
The used water-insoluble material of the present invention comprises pharmaceutically useful water-insoluble macromolecular material and pharmaceutically useful water-insoluble solid-state organic ester, solid-state organic alcohol, solid organic acid.The former comprises polyacrylic resin, cellulose acetate-phthalate, Hydroxypropyl Methylcellulose Phathalate, ethyl cellulose; The latter comprises cholesterol, tripalmitin, cholesterol ester stearic acid, Oleum Ricini wax, Brazil wax, stearic acid, octadecanol, spermol.Contain in the oral membrane of the present invention and be selected from least a in the above-mentioned water-insoluble material.
The used pharmaceutically acceptable water-soluble high-molecular material of the present invention is selected from least a in cellulose derivative, polyvinyl alcohol, gelatin, arabic gum, agar, alginic acid and salt thereof, starch, dextrin, zein, carbomer, poloxamer, polyvinyl alcohol, polyvinylpyrrolidone, Polyethylene Glycol, the starch derivatives.
Another aspect of the present invention provides the method for preparing above-mentioned oral membrane, and it comprises following processing step:
(1) with solvent 1 with adjuvant 10 ℃ of-100 ℃ of dissolving, or with adjuvant 1 after 50 ℃ of-100 ℃ of meltings, again medicine is added in the aforesaid liquid, make its dissolving or be uniformly dispersed, A liquid, wherein said adjuvant 1 comprises at least a in the insoluble macromolecular material of the pharmaceutically acceptable water that is insoluble to solvent 2, solid-state organic ester, solid-state organic alcohol, the solid-state organic acid;
(2) usefulness solvent 20 ℃ of-100 ℃ of dissolving, gets B liquid with adjuvant 2, and wherein adjuvant 2 comprises at least a pharmaceutically acceptable water-soluble high-molecular material, can also comprise or not comprise correctives;
(3) under 0 ℃-100 ℃ temperature, A liquid is added in the B liquid, add plasticizer again, spare 5 minutes to 2 hours with agitator stirring or dispersing emulsification machine breast, make two kinds of solution disperse mixing mutually, obtain finely dispersed liquid;
(4) adopt solvent method, extrusion molding or casting filming therapy that aforesaid liquid is made oral film preparation.
In the above-described method, by weight percentage, in the wherein said A liquid, solvent 1 accounts for the 0-98.9% of A liquid total amount, adjuvant 1 accounts for the 1-99.5% of A liquid total amount, and pharmaceutical compositions accounts for the 0.1-40% of A liquid total amount, and the water-insoluble material in the adjuvant 1 accounts for the 50-100% of adjuvant 1 total amount; In the B liquid, solvent 2 accounts for the 40-99% of B liquid total amount, and adjuvant 2 accounts for the 1-60% of B liquid total amount, and the water-soluble high-molecular material in the adjuvant 2 accounts for the 50-100% of adjuvant 2 total amounts; The ratio of A liquid and B liquid is counted by weight: 1: 0.1-100.
As previously discussed, feature of the present invention is to contain water solublity and water-insoluble two kinds of materials in the oral membrane simultaneously, correctives is embedded in the water-soluble high-molecular material film former, there is the medicine of bad smell then to be embedded in the water-insoluble material, utilize the immiscible character of water-insoluble material and water-soluble solution, the chemical compound of bad smell can not discharged in the oral cavity, thereby reach purpose of the present invention.Therefore, in the method for the present invention, when preparation A liquid,, except that comprising at least a water-insoluble material, can also contain surfactant, in the adjuvant 1 as Tween 80 according to the dissolving and the dispersive property of medicine in solvent.Adjuvant 2 also can contain correctives such as spice, sweeting agent etc. except that comprising the water-soluble high-molecular material film former, with further mouthfeel when improving membrane and taking.
Said solvent 1 is selected from one or more the mixture in alcohols, esters, ethers, acids, ketone, alkanes, the low molecular poly, the mixture of one or more in preferred alcohol, acetone, ethyl acetate, the isopropyl alcohol in the said method; Solvent 2 is selected from one or more the mixture in water, alcohols, acids, the low molecular poly, preferred water.
In A liquid of the inventive method and the B liquid blend step, the ratio of A liquid and B liquid will be in suitable scope, and can add plasticizer, makes two kinds of abundant mixings of liquid, and is not stratified, helps film forming.Plasticizer commonly used has at least a in glycerol, propylene glycol, Macrogol 200, PEG400, Macrogol 600, citron acid esters, the phthalic acid ester, and its consumption is the 0.01%-10% of A liquid and B liquid gross weight.
Solvent method, extrusion molding or casting filming therapy that the present invention adopts are the conventional film-forming methods that uses in the art.
By membrane disintegrate in 2 minutes in water of the prescription of oral film compositions provided by the present invention and preparation method preparation, the medicine in the membrane in water in 1 minute dissolution less than dissolution in 10%, 5 minute less than 50%.More preferably membrane can disintegrate in 1 minute in water, the membrane Chinese medicine in water in 1 minute dissolution less than dissolution in 2%, 5 minute less than 10%.
The prescription of oral film compositions provided by the present invention and preparation method compared with prior art have following advantage: the oral film preparation that 1, makes mouthfeel when taking is good, easy-to-swallow, is applicable to the patient of child, old man and dysphagia.2, preparation method is simple, and in preparation process, the mixed liquor that adopts film technique will comprise medicine is directly made oral film preparation, has avoided conventional method to need process with the embedding microgranule solidify, separates out, washs, dry refabrication afterwards becomes corresponding dosage form.
The specific embodiment
The present invention is described in more detail by the following examples, but the present invention is not subjected to any restriction of these embodiment.By the difference of oral membrane aspects such as dissolution in dissolution, the simulated gastric fluid in mouthfeel, disintegration, water of contrast experiment's example and embodiment of the invention gained relatively, thereby verify superiority of the present invention.
Contrast experiment's example 1 usefulness hydroxypropyl methylcellulose prepares the oral membrane of racecadotril
Prescription:
Hydroxypropyl methylcellulose 250g
Aspartame 15g
Chocolate essence 2g
Mentholum 9g
Purified water 1000ml
Racecadotril 50g
Ethanol 500ml
Plasticizer:
Glycerol 15ml
Preparation method:
Adopt the water-soluble film forming agent hydroxypropyl methylcellulose to prepare the oral film preparation of racecadotril.Hydroxypropyl emthylcellulose (HPMC) is added swelling in the purified water, and room temperature is used the agitator stirring and dissolving down, aspartame, chocolate essence and water solublity Herba Menthae brain is added successively stirring and dissolving again; After in addition racecadotril being dissolved in ethanol, under the room temperature this racecadotril alcoholic solution is added in the HPMC aqueous solution, add the plasticizer glycerol again, stirred 40 minutes, leave standstill the degassing after, adopt casting filming therapy, it is dry to extend on the polyester stripping film, obtain thickness and be 100 microns film, according to dosage cut apart, packing promptly.
Contrast experiment's example 2 usefulness polyacrylic resins prepare the oral membrane of racecadotril
Prescription:
Polyacrylic resin 250g
Racecadotril 50g
Aspartame 15g
Fructus Citri Limoniae essence 2g
Mentholum 9g
Ethanol 500ml
Plasticizer:
Glycerol 15ml
Preparation method:
Adopt water-insoluble film former polyacrylic resin to prepare the oral membrane of racecadotril.Under 70 ℃ polyacrylic resin is dissolved in the ethanol, place and again racecadotril, Mentholum to be added successively after the room temperature and make its dissolving, add the plasticizer glycerol then, stirred 40 minutes, after leaving standstill the degassing, adopt casting filming therapy, it is dry to extend on the polyester stripping film, obtain thickness and be 100 microns film, according to dosage cut apart, pack promptly.
Embodiment 1: prepare the oral membrane of racecadotril with hydroxypropyl methylcellulose, polyacrylic resin film former
Prescription:
A liquid:
Polyacrylic resin 100g
Racecadotril 50g
Ethanol 500ml
B liquid:
Hydroxypropyl methylcellulose 150g
Aspartame 15g
Chocolate essence 2g
Mentholum 9g
Purified water 1000ml
Plasticizer:
Glycerol 15ml
Preparation method:
Adopt water-soluble film forming agent hydroxypropyl methylcellulose and water-insoluble film former polyacrylic resin to prepare the oral film preparation of racecadotril.70 ℃ are dissolved in polyacrylic resin in the ethanol, racecadotril are dissolved in the alcoholic solution of above-mentioned polyacrylic resin after placing room temperature again, are prepared into A liquid.Hydroxypropyl emthylcellulose is added swelling in the purified water, and room temperature is used the agitator stirring and dissolving down, aspartame, chocolate essence and water solublity Herba Menthae brain is added successively again, and stirring and dissolving is prepared into B liquid.Under the room temperature A liquid is added in the B liquid, adds glycerol, stirred 40 minutes, leave standstill the degassing after, adopt casting filming therapy, it is dry to extend on the polyester stripping film, obtains thickness and be 100 microns film, according to dosage cuts apart, and packs promptly.
Embodiment 1 is compared with the oral membrane of contrast experiment's example 1, contrast experiment's example 2 gained, and the method for inspection of employing is as follows:
(1) mouthfeel: allow 10 volunteers will with distinct methods preparation but weight is identical, the membrane that content of dispersion is identical is put into mouth and was chewed 2 minutes, relatively taste and film are in the degree of dissolved in oral cavity.
(2) disintegration: according to two ones of Chinese Pharmacopoeia versions in 2005, appendix XA detects.Getting 6 in the sample of different preparation methoies preparation respectively, add baffle plate, is that 37 ℃ water is that medium detects with temperature, and the record membrane is the time by screen cloth all.
(3) dissolution: with water is the sample that medium detects different preparation methoies.With the octadecyl silane is filler; With 0.5% phosphoric acid solution (containing 0.5% triethylamine)-acetonitrile (64: 36) ammonia adjust pH is 5.0 as mobile phase; The detection wavelength is 210nm.Theoretical cam curve all should be not less than 3000 in racecadotril.
Get the sample of different preparation methoies, according to dissolution method (two appendix XC first methods of Chinese Pharmacopoeia version in 2005), with water 1000ml is medium, rotating speed is that per minute 100 changes, and solution 3ml is respectively got in operation during respectively at 1 minute, 5 minutes, 30 minutes in accordance with the law, filter, get subsequent filtrate 1ml and put in the 10ml measuring bottle, be diluted to scale with mobile phase, as need testing solution.It is an amount of that precision takes by weighing the racecadotril reference substance in addition, puts in the 50ml measuring bottle, with the mobile phase dissolving, and is diluted to scale; Get 1ml and put in the 100ml measuring bottle, be diluted to scale, in contrast product solution with mobile phase.Get each 50ul of reference substance solution and need testing solution respectively and inject chromatograph of liquid, the record chromatogram is by the dissolution of external standard method calculating membrane.
The comparison of the different membrane of table 1
Contrast experiment's example 1 adopts water-soluble film forming agent, in water disintegrate fast, in the oral cavity, can dissolve, easy-to-swallow; But stripping is fast in water, for the more serious racecadotril of bad mouthfeel, even add a large amount of correctivess, can not improve its bitterness.Contrast experiment's example 2 is selected water-insoluble film material for use, not disintegrate in water, and stripping quantity is little, and is insoluble in the oral cavity, can avoid the stripping of racecadotril bitterness; But monoblock membrane dysphagia is especially for the patient of child and dysphagia.The method that embodiment 1 adopts is that water soluble film-forming material and water-insoluble filmogen are made the system of disperseing homogeneous and prepared film forming, in water disintegrate fast, stripping is slow, after oral, hydroxypropyl methylcellulose dissolves in the oral cavity, discharges correctives, make membrane softening simultaneously, be broken into fritter; Racecadotril is embedded in the polyacrylic resin, and is little to the mouthfeel influence; Behind mixing in water for oral taking, membrane discharges chemical compound in vivo, and whole sensation mouthfeel is good, easy-to-swallow.
Embodiment 2-17 presses table 2,3 prescription and technological parameter, and prepares oral membrane according to embodiment 1 described method.
Prescription (the unit: g) of table 2 embodiment 2-9
The table 3 embodiment 10-17 (unit: g) of filling a prescription
Dissolution in the mouthfeel of the membrane of detection embodiment 2 to 17 preparations, disintegration, the water the results are shown in Table 4.
The testing result of table 4 embodiment 2 to 17
Embodiment 18: prepare the oral film preparation of Pitavastatin with octadecanol, hydroxypropyl emthylcellulose film former
Prescription:
A liquid:
Octadecanol 30g
Pitavastatin 10g
Tween 80 5g
B liquid:
Hydroxypropyl emthylcellulose 350g
Aspartame 8g
Fructus Citri Limoniae essence 2g
Water solublity Herba Menthae brain 9g
Purified water 1300ml
Plasticizer:
Glycerol 10ml
Preparation method:
Octadecanol is heated to 50 ℃ of meltings, again Pitavastatin, Tween 80 is joined in the octadecanol, stir, be prepared into A liquid.Hydroxypropyl emthylcellulose is added swelling in the purified water, and the dissolving of room temperature magnetic stirrer adds saccharin sodium, Fructus Citri Limoniae essence and water solublity Herba Menthae brain more successively, and stirring and dissolving is prepared into B liquid.50 ℃ add A liquid in the B liquid, add the plasticizer glycerol again, stir 1 hour, adopt casting filming therapy, and the drying that extends on the polyester stripping film obtains thickness and be 80 microns film, according to dosage cuts apart, packs promptly.
Embodiment 19-21 presses the prescription and the technological parameter of table 5, and prepares oral membrane according to embodiment 18 described methods.
Table 5 embodiment 19 to 21 prescription (units: g)
Dissolution in the mouthfeel of the membrane of inspection embodiment 18 to 21 preparations, disintegration, the water the results are shown in Table 6.
The testing result of table 6 embodiment 19-21
Above embodiment is not of the present invention whole, in parameter area of the present invention, all can realize effect of the present invention.
Claims (5)
1. the oral film compositions that can cover the active medicine bad smell, it is characterized in that said composition comprises: a kind of active medicine that bad smell is arranged, at least a in pharmaceutically useful water-insoluble macromolecular material, solid-state organic ester, solid-state organic alcohol, the solid-state organic acid, pharmaceutically useful water-soluble high-molecular material; Wherein active medicine and medicinal water-insoluble macromolecular material and/or solid-state organic ester, solid-state organic alcohol, solid-state organic acid ratio are 1: 1-10, and medicinal water-insoluble macromolecular material and/or solid-state organic ester, solid-state organic alcohol, solid-state organic acid and the ratio of medicinal soluble macromolecular material are 1: 0.5-50;
Described pharmaceutically useful water-insoluble macromolecular material is selected from polyacrylic resin, cellulose acetate-phthalate, Hydroxypropyl Methylcellulose Phathalate, ethyl cellulose; The insoluble solid-state organic ester of pharmaceutically acceptable water, solid-state organic alcohol, solid organic acid are selected from cholesterol, tripalmitin, cholesterol ester stearic acid, Oleum Ricini wax, Brazil wax, stearic acid, octadecanol, spermol;
Described pharmaceutically acceptable water-soluble high-molecular material be selected from carboxymethyl cellulose, hydroxypropyl emthylcellulose, polyvinyl alcohol, gelatin, arabic gum, agar, alginic acid and salt thereof, starch, dextrin, zein, carbomer, poloxamer,, polyvinylpyrrolidone, Polyethylene Glycol, carboxymethyl starch sodium.
2. oral film compositions according to claim 1, wherein said active medicine is selected from: racecadotril, Roxithromycin, voglibose, Mitiglinide, Entecavir, Navoban (Soz), loratadine, desloratadine, fluoxetine, Sertraline, citalopram, Zaleplon, sldenafil, Zolmitriptan, meloxicam, breviscapine, memantine, finasteride, lansoprazole, tamoxifen, voriconazole, valsartan, simvastatin, lovastatin, Pitavastatin, atorvastatin, nifedipine, amlodipine, TANSHINONES, bilobalide, ginkgetin, Yixintong.
3. the preparation method of oral membrane according to claim 1 and 2, it may further comprise the steps:
(1) with solvent 1 with adjuvant 10 ℃ of-100 ℃ of dissolving, or with adjuvant 1 after 50 ℃ of-100 ℃ of meltings, again medicine is added in the aforesaid liquid, make its dissolving or be uniformly dispersed, A liquid, wherein said adjuvant 1 comprises at least a in the insoluble macromolecular material of the pharmaceutically acceptable water that is insoluble to solvent 2, solid-state organic ester, solid-state organic alcohol, the solid-state organic acid;
(2) usefulness solvent 20 ℃ of-100 ℃ of dissolving, gets B liquid with adjuvant 2, and wherein adjuvant 2 comprises at least a pharmaceutically useful water-soluble high-molecular material, also comprises or do not comprise correctives;
(3) under 0 ℃-100 ℃ temperature, A liquid is added in the B liquid, add plasticizer again, spare 5 minutes to 120 minutes with agitator stirring or dispersing emulsification machine breast, make two kinds of solution disperse mixing mutually, obtain finely dispersed liquid;
(4) adopt solvent method, extrusion molding or casting filming therapy that aforesaid liquid is made membrane.
4. method according to claim 3, wherein said solvent 1 are one or more the mixture in ethanol, acetone, ethyl acetate, isopropyl alcohol, the low molecular poly; Solvent 2 is one or more the mixture in water, the low molecular poly.
5. method according to claim 3, by weight percentage, in the wherein said A liquid, solvent 1 accounts for the 0-98.9% of A liquid total amount, adjuvant 1 accounts for the 1-99.5% of A liquid total amount, and pharmaceutical compositions accounts for the 0.1-40% of A liquid total amount, and the water-insoluble material in the adjuvant 1 accounts for the 50-100% of adjuvant 1 total amount; In the B liquid, solvent 2 accounts for the 40-99% of B liquid total amount, and adjuvant 2 accounts for the 1-60% of B liquid total amount, and the water-soluble high-molecular material in the adjuvant 2 accounts for the 50-100% of adjuvant 2 total amounts; The ratio of A liquid and B liquid is counted by weight: 1: 0.1-100.
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| CN2007101181038A CN101084884B (en) | 2007-06-28 | 2007-06-28 | Oral film composition capable of masking pharmaceutical unpleasant flavor and preparation method thereof |
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| CN2007101181038A CN101084884B (en) | 2007-06-28 | 2007-06-28 | Oral film composition capable of masking pharmaceutical unpleasant flavor and preparation method thereof |
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| CN101084884B true CN101084884B (en) | 2010-12-08 |
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Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732286B (en) * | 2010-01-22 | 2012-01-04 | 上海现代药物制剂工程研究中心有限公司 | Voglibose film and preparation method thereof |
| CN102048730A (en) * | 2010-12-10 | 2011-05-11 | 浙江昂利康制药有限公司 | Levamlodipine besylate composition and preparation method thereof |
| CN102166197B (en) * | 2011-04-25 | 2012-09-05 | 四川百利药业有限责任公司 | Racecadotril granules and production process thereof |
| CN102824333B (en) * | 2012-09-26 | 2014-05-14 | 苏州大学 | Oral quick-dissolving film preparation and preparation method thereof |
| CN103800306B (en) * | 2013-12-18 | 2020-06-19 | 重庆医药工业研究院有限责任公司 | Memantine oral membrane and preparation method thereof |
| CN103816136A (en) * | 2013-12-20 | 2014-05-28 | 重庆医药工业研究院有限责任公司 | Dutasteride oral cavity film agent and preparation method thereof |
| CN104306354A (en) * | 2014-09-24 | 2015-01-28 | 万特制药(海南)有限公司 | Finasteride oral instant membrane |
| CN104188940A (en) * | 2014-09-26 | 2014-12-10 | 天津市聚星康华医药科技有限公司 | Simvastatin oral instant film and preparation method thereof |
| CN105919982A (en) * | 2016-06-30 | 2016-09-07 | 合肥华方医药科技有限公司 | Racecadotril oral fast dissolving film and preparation method thereof |
| CN114917205A (en) * | 2017-11-24 | 2022-08-19 | 江苏恒瑞医药股份有限公司 | Oral dissolving film composition |
| CN108451935A (en) * | 2018-04-12 | 2018-08-28 | 天津双硕医药科技有限公司 | A kind of solid composite medicament containing Mitiglinide Calcium |
| CN111388455B (en) * | 2020-04-09 | 2022-09-02 | 沈阳药科大学 | Everolimus oral film and preparation method thereof |
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