CN103142608A - Codeine phosphate and promethazine hydrochloride compound membranous preparation - Google Patents
Codeine phosphate and promethazine hydrochloride compound membranous preparation Download PDFInfo
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- CN103142608A CN103142608A CN2013100629771A CN201310062977A CN103142608A CN 103142608 A CN103142608 A CN 103142608A CN 2013100629771 A CN2013100629771 A CN 2013100629771A CN 201310062977 A CN201310062977 A CN 201310062977A CN 103142608 A CN103142608 A CN 103142608A
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Abstract
The invention discloses a codeine phosphate and promethazine hydrochloride compound membranous preparation. The codeine phosphate and promethazine hydrochloride compound membranous preparation comprises membranous strips, codeine phosphate and promethazine hydrochloride; the codeine phosphate and the promethazine hydrochloride are loaded on the membranous strips in therapeutically effective amount; the membranous strips comprise acidic membranous strips and alkaline membranous strips which are connected into a whole body and arranged at intervals; each acidic membranous strip takes a highly water-soluble polymer film-forming material as a main body and comprises 1-20% by weight of acidic agent; each acidic membranous strip takes a highly water-soluble polymer film-forming material as a main body and comprises 1-20% by weight of acidic agent; the codeine phosphate or the promethazine hydrochloride is loaded on the acidic membranous strips or the alkaline membranous strips. The codeine phosphate and promethazine hydrochloride compound membranous preparation can become an effervescent film in water to dull the sense of smell and mask smell, is high in dissolution speed and is low in interaction of different components of the preparation.
Description
Technical field
The present invention relates to codeine phosphate and promethazine hydrochloride compound preparation, be specifically related to contain the medicine film preparation of codeine phosphate and promethazine hydrochloride compound recipe.
Background technology
Codeine phosphate can directly suppress the coughing centre of medulla oblongata, and antitussive action is rapid and powerful, and its action intensity is about 1/4 of morphine.Analgesic activity is also arranged, be about 1/12～1/7 of morphine, but be better than general antipyretic analgesic.The effect such as its respiration inhibition, constipation, toleration and addiction is all than a little less than morphine.Promethazine hydrochloride is histamine H 1 receptor's antagonist, can be to the telangiectasis due to antianaphylaxis, reduce the permeability of blood capillary, panting due to the alleviation bronchial smooth muscle shrinks, antihistamine effect is more lasting, also have obvious central inhibitory action, can increase the effect of anesthetics, analgesic, hypnotic and local anaesthetics.Thereby codeine phosphate commonly used and the cough of promethazine hydrochloride compound treatment clinically, have obvious antitussive and certain antihistamine effect, be applicable to violent dry cough and irritable cough, comprise that upper respiratory tract infection, throat and bronchus stimulate cough, expectoration, dry cough or the allergic cough who causes.Especially be applicable to the violent dry cough person with chest pain.With its preparation patent medicine film preparation, need use water delivery service, be placed on tongue instantly, especially be fit to the child, improve patient's compliance, be subject to patient's 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, 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, 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.Passion for Life Healthcare company develops and the product of the prevention of a kind of uniqueness of having gone on the market snoring
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, 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 (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 entry, both react, 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 aqueous solvent together with active constituents of medicine, repastes the cloth drying and forming-film.Acidizer in effervescent and alkaline agent react in the with slurry process, can't retain in film simultaneously.When 2) preparing the compound recipe membrane, because the physicochemical property of the active component in 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 a kind of codeine phosphate and the membranaceous preparation of promethazine hydrochloride compound recipe, the defective that exists to overcome prior art satisfies clinical needs.
Described codeine phosphate and the membranaceous preparation of promethazine hydrochloride compound recipe comprise codeine phosphate and the promethazine hydrochloride 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 space arranges, refers to, and when being provided with many acid strip film bands and alkaline strip film band, acid strip film band and the space setting of alkaline strip film band;
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;
A kind of loading on respectively on acid strip film band or alkaline strip film band in described codeine phosphate or promethazine hydrochloride;
Preferably, described acid strip film band and alkaline strip film band also comprise more than one in plasticizer, correctives, coloring agent or stabilizing agent;
Preferably, described acid strip film band comprises the component of following percentage by weight:
Codeine phosphate or promethazine hydrochloride 0～30%, preferred 10～30%;
Highly-water-soluble macromolecule filming material 40～98%, preferred 45～70%;
Stabilizing agent 0～5%, preferred 0～1%;
Described alkaline strip film band comprises the component of following percentage by weight:
Codeine phosphate or promethazine hydrochloride 0～30%, preferred 10～30%;
Highly-water-soluble macromolecule filming material 40～98%, preferred 45～70%;
Stabilizing agent 0～5%, preferred 0～1%;
In the gross weight of described membranaceous preparation, the content of described codeine phosphate or promethazine hydrochloride is 1～30%, and is preferred 5～15%, and the weight ratio of codeine phosphate and promethazine hydrochloride is: codeine phosphate: promethazine hydrochloride=1: 0.625;
Described membranaceous preparation thickness is 0.04～0.20mm, preferred 0.06～0.10mm;
The invention still further relates to codeine phosphate and the membranaceous preparation of promethazine hydrochloride compound recipe that another kind is provided with blank tape, described codeine phosphate and the membranaceous preparation of promethazine hydrochloride compound recipe that is provided with blank tape, comprise blank tape, described blank tape is arranged between described acid strip film band and 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;
A kind of loading on respectively on acid strip film band or alkaline strip film band in described codeine phosphate or promethazine hydrochloride;
Preferably, described blank tape also comprises more than one in plasticizer, correctives, coloring agent or 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 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.;
Preferably:
Described acid strip film band comprises the component of following percentage by weight:
Codeine phosphate or promethazine hydrochloride 0～30%, preferred 10～30%;
Highly-water-soluble macromolecule filming material 40～98%, preferred 45～70%;
Stabilizing agent 0～5%, preferred 0～1%;
Described alkaline strip film band comprises the component of following percentage by weight:
Codeine phosphate or promethazine hydrochloride 0～30%, preferred 10～30%;
Highly-water-soluble macromolecule filming material 40～98%, preferred 45～70%;
Stabilizing agent 0～5%, preferred 0～1%;
Described blank tape comprises the component of following percentage by weight:
Highly-water-soluble macromolecule filming material 60～100%, preferred 75～99.9%;
Stabilizing agent 0～5%, preferred 0～1%;
In the gross weight of described membranaceous preparation, the content of described codeine phosphate or promethazine hydrochloride is 1～30%, preferred 5～15%;
The weight ratio of codeine phosphate and promethazine hydrochloride is: codeine phosphate: promethazine hydrochloride=1: 0.625;
The preparation method of described codeine phosphate and the membranaceous preparation of promethazine hydrochloride compound recipe comprises the steps:
(1) codeine phosphate or promethazine hydrochloride, acidizer and other adjuvants are mixed with water, the acquisition weight concentration is 15～35% water slip, makes acid serosity A;
(2) codeine phosphate or promethazine hydrochloride, alkaline agent and other adjuvants are mixed with water, the acquisition weight concentration is 15～35% water slip, makes alkaline slurry B;
When step (1) employing codeine phosphate, step (2) adopts promethazine hydrochloride;
When step (1) employing promethazine hydrochloride, step (2) adopts codeine phosphate;
(3) serosity A and serosity B are coated on flat board at the interval successively, due to the solvent expansion effect, are complex as a whole, obtain the medicine carrying thin film;
Term " interval coating successively " 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, obtain described membranaceous preparation at the temperature of 50～90 ℃.
Need to prove, when the content of certain component is 0, during preparation, do not add.
Further, comprise the preparation method of codeine phosphate and the membranaceous preparation of promethazine hydrochloride compound recipe of blank tape, comprise the steps:
(1) codeine phosphate or promethazine hydrochloride, acidizer and other adjuvants are mixed with water, the acquisition weight concentration is 15～35% water slip, makes acid serosity A;
(2) codeine phosphate or promethazine hydrochloride, alkaline agent and other adjuvants are mixed with water, the acquisition weight concentration is 15～35% water slip, makes alkaline slurry B;
When step (1) employing codeine phosphate, step (2) adopts promethazine hydrochloride;
When step (1) employing promethazine hydrochloride, step (2) adopts codeine phosphate;
(3) adjuvant is mixed with water, the acquisition weight concentration is 15～35% water slip, makes blank serosity C;
(4) serosity A, serosity B and blank serosity C are coated on flat board at the interval successively, due to the solvent expansion effect, are complex as a whole, obtain the medicine carrying thin film;
(5) the medicine carrying thin film that step (4) is obtained, dry 5～30min, obtain described compound membranaceous preparation at the temperature of 50～90 ℃.
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 a film, article one, contain the alkaline agents such as sodium carbonate, sodium bicarbonate or calcium carbonate in 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 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 codeine phosphate and promethazine hydrochloride.
Fig. 2 is codeine phosphate and the membranaceous preparation structure schematic diagram of promethazine hydrochloride with blank tape.
Fig. 3 is codeine phosphate and the promethazine hydrochloride film stripping curve of embodiment 1.
Fig. 4 is codeine phosphate and the promethazine hydrochloride film stripping curve of embodiment 2.
Fig. 5 is codeine phosphate and the promethazine hydrochloride film stripping curve of embodiment 5.
Fig. 6 is codeine phosphate and the promethazine hydrochloride film stripping curve of embodiment 6.
The specific embodiment
Referring to Fig. 1, the membranaceous preparation of described codeine phosphate and promethazine hydrochloride 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 codeine phosphate and promethazine hydrochloride also comprises blank tape 3, described blank tape 3 is arranged between described acid strip film band 1 and alkaline strip film band 2, and is connected with described acid strip film band 1 and alkaline strip film band 2 respectively.
1) get codeine phosphate 50g adding distil water 500ml, stir, be uniformly dispersed, then add successively tartaric acid 20g while stirring, stevioside 20g and titanium dioxide 10g, add at last PVA100g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get promethazine hydrochloride 31.25g adding distil water 700ml, stir, be uniformly dispersed, add successively while stirring again potassium bicarbonate 20g, stevioside 20g and titanium dioxide 10g, add at last PVA118.75g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get 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 the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 15min, due to 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, after cutting into certain size, 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 0.08mm, every phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Take every day 3 times.More than 12 years old, child and adult one time are 2～4; 1～2 of 6～12 years old child one time; 0.5～1 of 2～6 years old child one time.
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 A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, observe and record that membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 55 ± 3s.
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X C the second methods of Chinese Pharmacopoeia version in 2010) device, take 0.1M hydrochloric acid solution 500ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately is respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate the stripping quantity of every according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).Its In Vitro Dissolution curve is seen Fig. 3.As seen from Figure 3, the In Vitro Dissolution of codeine phosphate of the present invention and promethazine hydrochloride compound recipe film is very fast, and codeine phosphate and promethazine hydrochloride be dissolve complete in 5min all.
1) get promethazine hydrochloride 31.25g adding distil water 500ml, stir, be uniformly dispersed, add successively while stirring again glycerol 10g, citric acid 4g, sucralose 10g, taste masking resin 50g, EDTA-2Na 0.75g and titanium dioxide 4g, add at last maltodextrin 40g and corn starch 50g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get codeine phosphate 50g adding distil water 500ml, stir, be uniformly dispersed, add successively while stirring again glycerol 10g, potassium carbonate 4g, aspartame 10g and titanium dioxide 4g, add at last HPMC122g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get 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 the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 70 ℃ of dry 20min, due to 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, after cutting into certain size, 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 0.08mm, every phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Take every day 3 times.More than 12 years old, child and adult one time are 2～4; 1～2 of 6～12 years old child one time; 0.5～1 of 2～6 years old child one time.
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 A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, observe and record that membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 54 ± 5s.
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X C the second methods of Chinese Pharmacopoeia version in 2010) device, take 0.1M hydrochloric acid solution 500ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately is respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate the stripping quantity of every according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).Its In Vitro Dissolution curve is seen Fig. 4.As seen from Figure 4, the In Vitro Dissolution of codeine phosphate of the present invention and promethazine hydrochloride compound recipe film is very fast, and codeine phosphate and promethazine hydrochloride be dissolve complete in 5min all.
1) get promethazine hydrochloride 37.5g adding distil water 500ml, dispersed with stirring is even, add while stirring again aspartame 30g, vitamin E2 g, glycerol 4g, erythrosine pigment 0.2g and malic acid 4g, add at last PVA100g and corn starch 22.3g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get codeine phosphate 60g adding distil water 500ml, dispersed with stirring is even, then adds while stirring aspartame 30g, vitamin E2 g, glycerol 4g, erythrosine pigment 0.2g and sodium bicarbonate 4g, add at last PVA99.8g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get 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 the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 90 ℃ of dry 5min, due to 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, after cutting into certain size, 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, every phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Take every day 3 times.More than 12 years old, child and adult one time are 2～4; 1～2 of 6～12 years old child one time; 0.5～1 of 2～6 years old child one time.
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 A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, observe and record that membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 43 ± 4s.
Embodiment 4
1) get codeine phosphate 32g adding distil water 500ml, dispersed with stirring is even, then adds while stirring aspartame 30g, acesulfame potassium 5.8g, the red 0.2g of temptation and fumaric acid 4g, add at last HPC128g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get promethazine hydrochloride 20g adding distil water 500ml, dispersed with stirring is even, then adds while stirring taste masking resin 30g, acesulfame potassium 5.8g, the red 0.2g of temptation and sodium carbonate 4g, add at last HPC100g and maltodextrin 40g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get 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 the coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 30min, due to 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, after cutting into certain size, 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 0.10mm, every phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Take every day 3 times.More than 12 years old, child and adult one time are 2～4; 1～2 of 6～12 years old child one time; 0.5～1 of 2～6 years old child one time.
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 A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, observe and record that membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 66 ± 5s.
Embodiment 5
1) get codeine phosphate 50g, adding distil water 600ml stirs, and is uniformly dispersed, then adds while stirring maleic acid 20g, sucralose 15g and allured red pigment 0.3g, adds at last PEO114.7g, crosses 80 mesh sieves, removes insoluble matter, vacuum defoamation.Get serosity A.
2) get PEO32g, adding distil water 100ml is uniformly dispersed, then adds allured red pigment 0.02g and sunset yellow 0.05g, stirs, and crosses 80 mesh sieves, removes insoluble matter, vacuum defoamation.Get serosity B.
3) get promethazine hydrochloride 31.25g, adding distil water 600ml stirs, and is uniformly dispersed, then adds while stirring calcium carbonate 20g, sucralose 15g and allured red pigment 0.3g, adds at last PEO133.45g, crosses 80 mesh sieves, removes insoluble matter, vacuum defoamation.Get serosity C.
Serosity A, B and C are added in 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, 50 ℃ of dry 30min, due to 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, after cutting into certain size, 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, every phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Take every day 3 times.More than 12 years old, child and adult one time are 2～4; 1～2 of 6～12 years old child one time; 0.5～1 of 2～6 years old child one time.
This film preparation is comprised of trichroism, and is aesthetic in appearance, becomes the effervescent film after 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 A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, observe and record that membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 48 ± 3s.
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X C the second methods of Chinese Pharmacopoeia version in 2010) device, take 0.1M hydrochloric acid solution 500ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately is respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate the stripping quantity of every according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).Its In Vitro Dissolution curve is seen Fig. 5.As seen from Figure 5, the In Vitro Dissolution of codeine phosphate of the present invention and promethazine hydrochloride compound recipe film is very fast, and codeine phosphate and promethazine hydrochloride be dissolve complete in 5min all.
1) get codeine phosphate 50g, adding distil water 600ml stirs, and is uniformly dispersed, add while stirring again PEG40004g, citric acid 10g, saccharin sodium 5g, cyclamate 5g and titanium dioxide 10g, add at last HPC116g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get PVP4.75g and HPMC20g, adding distil water 100ml stirs, be uniformly dispersed, then add PEG40001.65g while stirring, acesulfame potassium 4.95g and titanium dioxide 1.65g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity B.
3) get promethazine hydrochloride 31.25g, adding distil water 600ml stirs, be uniformly dispersed, then add PEG40004g while stirring, sodium carbonate 10g, saccharin sodium 5g, cyclamate 5g and titanium dioxide 10g, add at last HPC134.75g, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity C.
Serosity A, B and C are added in 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 20min, due to 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, after cutting into certain size, 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, every phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Take every day 3 times.More than 12 years old, child and adult one time are 2～4; 1～2 of 6～12 years old child one time; 0.5～1 of 2～6 years old child one time.
This film preparation is aesthetic in appearance, becomes the effervescent film after 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 A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, observe and record that membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 53 ± 4s.
Get 6 of this product, clamp with paperclip respectively, adopt dissolution method (two appendix X C the second methods of Chinese Pharmacopoeia version in 2010) device, take 0.1M hydrochloric acid solution 500ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately is respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, measure and calculate the stripping quantity of every according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).Its In Vitro Dissolution curve is seen Fig. 6.As seen from Figure 6, the In Vitro Dissolution of codeine phosphate of the present invention and promethazine hydrochloride compound recipe film is very fast, and codeine phosphate and promethazine hydrochloride be dissolve complete in 5min all.
Embodiment 7
1) get codeine phosphate 50g, adding distil water 600ml stirs, and is uniformly dispersed, add while stirring again xylitol 13g, aspartame 15g, light blue pigment 0.2g, tartaric acid 10g and vitamin E2 g, add at last HPMC110g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity A.
2) get HPMC32.97g adding distil water 100ml, stir, then add light blue pigment 0.03g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity B.
3) get promethazine hydrochloride 31.25g, adding distil water 600ml, stir, be uniformly dispersed, then add while stirring xylitol 13g, aspartame 15g, light blue pigment 0.2g, sodium carbonate 10g and vitamin E2 g, add at last HPMC128.75g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Get serosity C.
Serosity A, B, C are added in dosing tank, and this dosing tank is comprised of three parallel sulculuses, and width is respectively 1.2cm, 0.2cm and 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 20min, due to 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, after cutting into certain size, 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, every phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Take every day 3 times.More than 12 years old, child and adult one time are 2～4; 1～2 of 6～12 years old child one time; 0.5～1 of 2～6 years old child one time.
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 A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, observe and record that membrane all dissolves and the time by screen cloth.It is very fast that this product is dissolved the time limit, is 55 ± 4s.
Claims (10)
1. codeine phosphate and the membranaceous preparation of promethazine hydrochloride compound recipe, is characterized in that, comprises codeine phosphate and the promethazine hydrochloride 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;
A kind of loading on respectively on acid strip film band or alkaline strip film band in described codeine phosphate or promethazine hydrochloride.
2. codeine phosphate according to claim 1 and the membranaceous preparation of promethazine hydrochloride compound recipe, is characterized in that, 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.
3. codeine phosphate according to claim 1 and the membranaceous preparation of promethazine hydrochloride compound recipe, 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. codeine phosphate according to claim 1 and the membranaceous preparation of promethazine hydrochloride compound recipe, 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 codeine phosphate or promethazine hydrochloride is 1～30%, and the weight ratio of codeine phosphate and promethazine hydrochloride is: codeine phosphate: promethazine hydrochloride=1: 0.625.
5. codeine phosphate according to claim 1 and the membranaceous preparation of promethazine hydrochloride compound recipe, 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 codeine phosphate or promethazine hydrochloride is 5～15%.
6. codeine phosphate and the membranaceous preparation of promethazine hydrochloride compound recipe, is characterized in that, comprises codeine phosphate and the promethazine hydrochloride of strip film band and load treatment effective dose thereon;
Described strip film band comprises blank tape, acid strip film band and alkaline strip film band, the described blank tape of establishing is put between described acid strip film band and 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 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;
A kind of loading on respectively on acid strip film band or alkaline strip film band in described codeine phosphate or promethazine hydrochloride.
7. codeine phosphate according to claim 6 and the membranaceous preparation of promethazine hydrochloride compound recipe, is characterized in that, 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.
8. codeine phosphate according to claim 6 and the membranaceous preparation of promethazine hydrochloride compound recipe, is characterized in that, described blank tape, acid strip film band and alkaline strip film band also comprise more than one in plasticizer, correctives, coloring agent or stabilizing agent.
9. codeine phosphate according to claim 6 and the membranaceous preparation of promethazine hydrochloride compound recipe, 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 codeine phosphate or promethazine hydrochloride is 1～30%, and the weight ratio of codeine phosphate and promethazine hydrochloride is: codeine phosphate: promethazine hydrochloride=1: 0.625.
10. according to claim 1～9 described codeine phosphates of any one and the membranaceous preparation of promethazine hydrochloride compound recipe, 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 carrageenan.
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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 |
| CN102028672A (en) * | 2010-09-29 | 2011-04-27 | 上海现代药物制剂工程研究中心有限公司 | Microporous spongy film preparation 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 |
| CN102028672A (en) * | 2010-09-29 | 2011-04-27 | 上海现代药物制剂工程研究中心有限公司 | Microporous spongy film preparation and preparation method thereof |
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