CN103142608B - Codeine phosphate and promethazine hydrochloride compound membranous preparation - Google Patents
Codeine phosphate and promethazine hydrochloride compound membranous preparation Download PDFInfo
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- CN103142608B CN103142608B CN201310062977.1A CN201310062977A CN103142608B CN 103142608 B CN103142608 B CN 103142608B CN 201310062977 A CN201310062977 A CN 201310062977A CN 103142608 B CN103142608 B CN 103142608B
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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 the medicine film preparation containing codeine phosphate and promethazine hydrochloride compound recipe.
Background technology
Codeine phosphate directly can suppress the coughing centre of medulla oblongata, and antitussive action is rapid and powerful, and its action intensity is about 1/4 of morphine.Also there is analgesic activity, be about 1/12 ~ 1/7 of morphine, but be better than general antipyretic analgesic.Its respiration inhibition, constipation, toleration and the effect such as additive are all weak compared with morphine.Promethazine hydrochloride is histamine H 1 receptor's antagonist, can to the telangiectasis caused by antianaphylaxis, reduce the permeability of blood capillary, alleviate panting caused by bronchial smooth muscle contraction, antihistamine effect is more lasting, also there is obvious central inhibitory action, the effect of anesthetics, analgesic, hypnotic and local anaesthetics can be increased.Thus conventional codeine phosphate and the cough of promethazine hydrochloride compound treatment clinically, there is obvious antitussive and certain antihistamine effect, be applicable to violent dry cough and irritable cough, comprise upper respiratory tract infection, throat and bronchus stimulate cause cough, expectoration, dry cough or allergic cough.Especially the violent dry cough person with chest pain is applicable to.Prepared patent medicine film preparation, do not need, with water delivery service, to be placed on tongue instant, be especially applicable to child, improve patient's compliance, be subject to patient and welcome; And its production technology is simple, power consumption is few, and cost is lower.
Medicine film preparation is as far back as nineteen seventies i.e. existing much research, 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.
But membrane is thin, light, little, the easy moisture absorption, thus to packaging requirement higher, should be easy to use, the quality of medicine should be able to be ensured again, and domestic current packaged form use inconvenience, unsightly; The drug loading of membrane is not high (general 30 ~ below 60mg), and will carry out taste masking.These all constrain development and the application of membrane.
In recent years, membrane development is swift and violent, and calendar year 2001 Pfizer company is proposed
with
product, for anti-halitosis in advance.Novartis company is also proposed the folk prescription or compound oral membrane that a series of effective ingredient is diphenhydramine, phenylephrine and dextromethorphan, for catching a cold, coughing or the Prevention and Curation of rhinitis.More pelliculae pro cavo oris product is had to occur subsequently.Pelliculae pro cavo oris technology is used for the product of physical strength reinforcing, vitimin supplement, hypersexuality and appetite-suppressing by Biofilm company.Ondansetron (ondansetron) membrane of MonosolRx company exploitation and its oral cavity quick disintegrating slice
bioequivalence, obtains the approval of FDA in July, 2010.Passion for Life Healthcare company develops and the product of the pre-anti-snoring of a kind of uniqueness of having gone on the market
voglibose (voglibose) membrane of Kyukyu yakuhin Kogyo K.K. of Japan development, released, for improving diabetics postprandial hyperglycemia in August, 2006.
Patent about membrane also emerges in an endless stream, there is the edible water-soluble film (CN101516331A) containing foam reducing flavoring agent, for the film bandage (CN101389309A) of mucosal administration of actives, high dose film compositions and preparation method thereof (CN101616660A), polymer-based films and drug delivery system prepared therefrom (CN101668519A), the preparation method (CN101744791A) of edible film, for the film (CN101346135A) of the adjusted pH that activating agent is sent, for the film bandage (CN101389309A) of mucosal administration of actives, non-mucoadhesive film dosage forms (CN101626756A), disintegrable oral films (CN101384249A), membrane (CN101621990A) that can be Orally administered, for neuroleptic, film (CN101287445A) can not be collapsed by the oral fast spued, instant capacity membrane (CN100396332C) etc.The present inventor has also applied for the patent of packaged form of the production machine of membrane, the packaging machine of membrane, the new of membrane, to promote membrane development at home.
The present 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 effective method to modify taste, effervescent is made up 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 temporary paralysis taste bud and taste masking.But in the process preparing 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) when preparing compound recipe membrane, because the physicochemical property of the active component in compound recipe is different, the prescription be applicable to and technique different, influence each other sometimes.The compound recipe be such as made up of A and B, acidic excipient can strengthen the stability of A material, but have impact on the dissolubility of B substance, and B is not easily uniformly dispersed in pulping process.
Summary of the invention
The object of this invention is to provide a kind of codeine phosphate and promethazine hydrochloride compound recipe film-like preparation, to overcome the defect that prior art exists, meet clinical needs.
Described codeine phosphate and promethazine hydrochloride compound recipe film-like preparation, comprise codeine phosphate and the promethazine hydrochloride of strip film strips and load treatment effective dose thereon;
Described strip film strips, comprises acidic strip film strips and alkaline strip film strips, and described acidic strip film strips and alkaline strip film strips are connected, and spaced setting; Described spaced setting, refers to when being provided with many acidic strip film strips and alkaline strip film strips, acidic strip film strips and the spaced setting of alkaline strip film strips;
Described acidic strip film strips, based on highly-water-soluble macromolecule filming material, with film strips weighing scale, the acidizer containing 1 ~ 20%, preferably 2 ~ 10%, described acidizer is selected from citric acid, tartaric acid, fumaric acid, maleic acid, adipic acid or malic acid;
Described alkaline strip film strips, based on highly-water-soluble macromolecule filming material, with film strips weighing scale, the alkaline agent containing 1 ~ 20%, preferably 2 ~ 10%, described alkaline agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or calcium carbonate;
One in described codeine phosphate or promethazine hydrochloride respectively load in acidic strip film strips or alkaline strip film strips;
Preferably, described acidic strip film strips and alkaline strip film strips, also comprise in plasticizer, correctives, coloring agent or stabilizing agent more than one;
Preferably, described acidic strip film strips comprises the component of following percentage by weight:
Codeine phosphate or promethazine hydrochloride 0 ~ 30%, preferably 10 ~ 30%;
Highly-water-soluble macromolecule filming material 40 ~ 98%, preferably 45 ~ 70%;
Acidizer 1 ~ 20%, preferably 2 ~ 10%;
Plasticizer 0 ~ 20%, preferably 0 ~ 5%;
Correctives 0 ~ 40%, preferably 5 ~ 30%;
Coloring agent 0 ~ 5%, preferably 0.1 ~ 5%;
Stabilizing agent 0 ~ 5%, preferably 0 ~ 1%;
Described alkaline strip film strips comprises the component of following percentage by weight:
Codeine phosphate or promethazine hydrochloride 0 ~ 30%, preferably 10 ~ 30%;
Highly-water-soluble macromolecule filming material 40 ~ 98%, preferably 45 ~ 70%;
Alkaline agent 1 ~ 20%, preferably 2 ~ 10%;
Plasticizer 0 ~ 20%, preferably 0 ~ 5%;
Correctives 0 ~ 40%, preferably 5 ~ 30%;
Coloring agent 0 ~ 5%, preferably 0.1 ~ 5%;
Stabilizing agent 0 ~ 5%, preferably 0 ~ 1%;
With the total weight of described film-like preparation, described codeine phosphate or the content of promethazine hydrochloride are 1 ~ 30%, preferably 5 ~ 15%, and the weight ratio of codeine phosphate and promethazine hydrochloride is: codeine phosphate: promethazine hydrochloride=1: 0.625;
Described film-like preparation thickness is 0.04 ~ 0.20mm, preferably 0.06 ~ 0.10mm;
The invention still further relates to codeine phosphate and promethazine hydrochloride compound recipe film-like preparation that another kind is provided with blank tape, described codeine phosphate and the promethazine hydrochloride compound recipe film-like preparation being provided with blank tape, comprise blank tape, described blank tape is arranged between described acidic strip film strips and alkaline strip film strips, and be connected with described acidic strip film strips and alkaline strip film strips respectively, described blank tape comprises highly-water-soluble macromolecule filming material;
One in described codeine phosphate or promethazine hydrochloride respectively load in acidic strip film strips or alkaline strip film strips;
Preferably, described blank tape also comprise in plasticizer, correctives, coloring agent or stabilizing agent more than one;
Described water soluble polymer filmogen comprise 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 more than one;
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 comprise in Polyethylene Glycol (PEG), glycerol or Tween 80 more than one;
Described correctives comprise in sweeting agent, acidic flavoring agent, aromatic, resin macromolecular material, lecithin, cephalin or phosphatidic acid etc. more than one;
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.;
Preferred:
Described acidic strip film strips comprises the component of following percentage by weight:
Codeine phosphate or promethazine hydrochloride 0 ~ 30%, preferably 10 ~ 30%;
Highly-water-soluble macromolecule filming material 40 ~ 98%, preferably 45 ~ 70%;
Acidizer 1 ~ 20%, preferably 2 ~ 10%;
Plasticizer 0 ~ 20%, preferably 0 ~ 5%;
Correctives 0 ~ 40%, preferably 5 ~ 30%;
Coloring agent 0 ~ 5%, preferably 0.1 ~ 5%;
Stabilizing agent 0 ~ 5%, preferably 0 ~ 1%;
Described alkaline strip film strips comprises the component of following percentage by weight:
Codeine phosphate or promethazine hydrochloride 0 ~ 30%, preferably 10 ~ 30%;
Highly-water-soluble macromolecule filming material 40 ~ 98%, preferably 45 ~ 70%;
Alkaline agent 1 ~ 20%, preferably 2 ~ 10%;
Plasticizer 0 ~ 20%, preferably 0 ~ 5%;
Correctives 0 ~ 40%, preferably 5 ~ 30%;
Coloring agent 0 ~ 5%, preferably 0.1 ~ 5%;
Stabilizing agent 0 ~ 5%, preferably 0 ~ 1%;
Described blank tape comprises the component of following percentage by weight:
Highly-water-soluble macromolecule filming material 60 ~ 100%, preferably 75 ~ 99.9%;
Plasticizer 0 ~ 20%, preferably 0 ~ 5%;
Correctives 0 ~ 30%, preferably 0 ~ 15%;
Coloring agent 0 ~ 5%, preferably 0.1 ~ 5%;
Stabilizing agent 0 ~ 5%, preferably 0 ~ 1%;
With the total weight of described film-like preparation, described codeine phosphate or the content of promethazine hydrochloride are 1 ~ 30%, preferably 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 promethazine hydrochloride compound recipe film-like preparation, comprises the steps:
(1) codeine phosphate or promethazine hydrochloride, acidizer and other adjuvants are mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained acid serosity A;
(2) codeine phosphate or promethazine hydrochloride, alkaline agent and other adjuvants are mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained alkaline slurry B;
When step (1) adopts codeine phosphate, then step (2) adopts promethazine hydrochloride;
When step (1) adopts promethazine hydrochloride, then step (2) adopts codeine phosphate;
(3) serosity A and serosity B successively interval is coated on flat board, due to solvent expansion effect, is complex as a whole, obtain medicine carrying thin film;
Term " interval coating successively ", refer to one for serosity A, other one is serosity B;
(4) by the medicine carrying thin film that step (3) obtains, dry 5 ~ 30min at the temperature of 50 ~ 90 DEG C, the film-like preparation described in acquisition.
It should be noted that, when the content of certain component is 0, during preparation, do not add.
Further, comprise the codeine phosphate of blank tape and the preparation method of promethazine hydrochloride compound recipe film-like preparation, comprise the steps:
(1) codeine phosphate or promethazine hydrochloride, acidizer and other adjuvants are mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained acid serosity A;
(2) codeine phosphate or promethazine hydrochloride, alkaline agent and other adjuvants are mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained alkaline slurry B;
When step (1) adopts codeine phosphate, then step (2) adopts promethazine hydrochloride;
When step (1) adopts promethazine hydrochloride, then step (2) adopts codeine phosphate;
(3) adjuvant is mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained blank serosity C;
(4) serosity A, serosity B and blank serosity C are coated on flat board in interval successively, due to solvent expansion effect, are complex as a whole, obtain medicine carrying thin film;
(5) by the medicine carrying thin film that step (4) obtains, dry 5 ~ 30min at the temperature of 50 ~ 90 DEG C, the composite film preparation described in acquisition.
It should be noted that, when the content of a certain component is 0, during preparation, namely do not add.
The using method of film-like preparation of the present invention is identical with conventional membrane.
The beneficial effect of film-like preparation of the present invention is:
The present inventor, by a large amount of experiments accumulation, is coated with two or more when being coated with simultaneously, final formation many composite film agent.Many film can realize following specific purposes: 1) make effervescent film: containing the acidizer 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, effervescent film is become after meeting water, produce a large amount of bubble, paralysis olfactory sensation and taste masking, and can stripping be accelerated.2) compound recipe film is prepared: can study the prescription of heterogeneity, technique respectively, the compound when being coated with, influencing each other in compound recipe between heterogeneity can be reduced, 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 codeine phosphate and promethazine hydrochloride film-like preparation structural representation.
Fig. 2 is codeine phosphate and the promethazine hydrochloride film-like preparation structural representation 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.
Detailed description of the invention
See Fig. 1, described codeine phosphate and promethazine hydrochloride film-like preparation, comprise acidic strip film strips 1 and alkaline strip film strips 2, and described acidic strip film strips 1 and alkaline strip film strips 2 are connected, and spaced setting.
See Fig. 2, preferably, described codeine phosphate and promethazine hydrochloride film-like preparation, also comprise blank tape 3, described blank tape 3 is arranged between described acidic strip film strips 1 and alkaline strip film strips 2, and is connected with described acidic strip film strips 1 and alkaline strip film strips 2 respectively.
Embodiment 1
1) get codeine phosphate 50g adding distil water 500ml, stir, be uniformly dispersed, then add tartaric acid 20g, stevioside 20g and titanium dioxide 10g while stirring successively, finally add PVA100g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity A.
2) get promethazine hydrochloride 31.25g adding distil water 700ml, stir, be uniformly dispersed, add potassium bicarbonate 20g, stevioside 20g and titanium dioxide 10g while stirring successively again, finally add PVA118.75g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity B.
Add in dosing tank by serosity A and serosity B, this dosing tank is made up 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 DEG C of dry 15min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt knurling rolls embossing again, according to 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 obtained, thickness is 0.08mm, every sheet phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Daily 3 times.More than 12 years old children and adult one time 2 ~ 4; 6 ~ 12 years old children one time 1 ~ 2; 2 ~ 6 years old children one time 0.5 ~ 1.
This medicine film preparation is aesthetic in appearance.Become effervescent film after meeting water, produce a large amount of bubble, stripping is rapid, and sense of taste is better.
Get this product 6, each clip becomes the thin film of 1cm × 1cm size, be the stainless steel silk folder of 2.0mm respectively with two-layer sieve aperture internal diameter, check according to the method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ A) under disintegration inspection technique tablet item, observe and record membrane and all to dissolve and by time of screen cloth.It is very fast that this product dissolves the time limit, is 55 ± 3s.
Get this product 6, clamp with paperclip respectively, adopt dissolution method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ C second methods) device, with 0.1M hydrochloric acid solution 500ml for dissolution medium, rotating speed is 50 turns per minute, from test sample contact dissolution medium, timing immediately, respectively through 1,2,3,5,10 and 15 minute time, get solution 1ml, filter, get subsequent filtrate, measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V D) and calculate the stripping quantity of every sheet.Its In Vitro Dissolution curve is shown in 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 all dissolve completely in 5min.
Embodiment 2
1) promethazine hydrochloride 31.25g adding distil water 500ml is got, stir, be uniformly dispersed, add glycerol 10g, citric acid 4g, sucralose 10g, taste masking resin 50g, EDTA-2Na 0.75g and titanium dioxide 4g more while stirring successively, finally add maltodextrin 40g and corn starch 50g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity A.
2) get codeine phosphate 50g adding distil water 500ml, stir, be uniformly dispersed, add glycerol 10g, potassium carbonate 4g, aspartame 10g and titanium dioxide 4g while stirring successively again, finally add HPMC122g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity B.
Add in dosing tank by serosity A and serosity B, this dosing tank is made up 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, 70 DEG C of dry 20min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt knurling rolls embossing again, according to 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 obtained, thickness is 0.08mm, every sheet phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Daily 3 times.More than 12 years old children and adult one time 2 ~ 4; 6 ~ 12 years old children one time 1 ~ 2; 2 ~ 6 years old children one time 0.5 ~ 1.
This medicine film preparation is aesthetic in appearance.Become effervescent film after meeting water, produce a large amount of bubble, stripping is rapid, and sense of taste is better.
Get this product 6, each clip becomes the thin film of 1cm × 1cm size, be the stainless steel silk folder of 2.0mm respectively with two-layer sieve aperture internal diameter, check according to the method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ A) under disintegration inspection technique tablet item, observe and record membrane and all to dissolve and by time of screen cloth.It is very fast that this product dissolves the time limit, is 54 ± 5s.
Get this product 6, clamp with paperclip respectively, adopt dissolution method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ C second methods) device, with 0.1M hydrochloric acid solution 500ml for dissolution medium, rotating speed is 50 turns per minute, from test sample contact dissolution medium, timing immediately, respectively through 1,2,3,5,10 and 15 minute time, get solution 1ml, filter, get subsequent filtrate, measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V D) and calculate the stripping quantity of every sheet.Its In Vitro Dissolution curve is shown in 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 all dissolve completely in 5min.
Embodiment 3
1) promethazine hydrochloride 37.5g adding distil water 500ml is got, dispersed with stirring is even, add aspartame 30g, vitamin E2 g, glycerol 4g, erythrosine pigment 0.2g and malic acid 4g more while stirring, finally add PVA100g and corn starch 22.3g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity A.
2) get codeine phosphate 60g adding distil water 500ml, dispersed with stirring is even, then adds aspartame 30g, vitamin E2 g, glycerol 4g, erythrosine pigment 0.2g and sodium bicarbonate 4g while stirring, finally add PVA99.8g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity B.
Add in dosing tank by serosity A and serosity B, this dosing tank is made up 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, 90 DEG C of dry 5min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt knurling rolls embossing again, according to 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 obtained, thickness is 0.06mm, every sheet phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Daily 3 times.More than 12 years old children and adult one time 2 ~ 4; 6 ~ 12 years old children one time 1 ~ 2; 2 ~ 6 years old children one time 0.5 ~ 1.
This medicine film preparation is aesthetic in appearance.Become effervescent film after meeting water, produce a large amount of bubble, stripping is rapid, and sense of taste is better.
Get this product 6, each clip becomes the thin film of 1cm × 1cm size, be the stainless steel silk folder of 2.0mm respectively with two-layer sieve aperture internal diameter, check according to the method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ A) under disintegration inspection technique tablet item, observe and record membrane and all to dissolve and by time of screen cloth.It is very fast that this product dissolves the time limit, is 43 ± 4s.
Embodiment 4
1) get codeine phosphate 32g adding distil water 500ml, dispersed with stirring evenly, then adds aspartame 30g, acesulfame potassium 5.8g while stirring, lures red 0.2g and fumaric acid 4g, finally add HPC128g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity A.
2) get promethazine hydrochloride 20g adding distil water 500ml, dispersed with stirring evenly, then adds taste masking resin 30g, acesulfame potassium 5.8g while stirring, lures red 0.2g and sodium carbonate 4g, finally add HPC100g and maltodextrin 40g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity B.
Add in dosing tank by serosity A and serosity B, this dosing tank is made up 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 DEG C of dry 30min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt knurling rolls embossing again, according to 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 obtained, thickness is 0.10mm, every sheet phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Daily 3 times.More than 12 years old children and adult one time 2 ~ 4; 6 ~ 12 years old children one time 1 ~ 2; 2 ~ 6 years old children one time 0.5 ~ 1.
This medicine film preparation is aesthetic in appearance.Become effervescent film after meeting water, produce a large amount of bubble, stripping is rapid, and sense of taste is better.
Get this product 6, each clip becomes the thin film of 1cm × 1cm size, be the stainless steel silk folder of 2.0mm respectively with two-layer sieve aperture internal diameter, check according to the method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ A) under disintegration inspection technique tablet item, observe and record membrane and all to dissolve and by time of screen cloth.It is very fast that this product dissolves the time limit, is 66 ± 5s.
Embodiment 5
1) get codeine phosphate 50g, adding distil water 600ml, stir, be uniformly dispersed, then add maleic acid 20g, sucralose 15g and allured red pigment 0.3g while stirring, finally add PEO114.7g, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain 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, removing insoluble matter, vacuum defoamation.Obtain serosity B.
3) get promethazine hydrochloride 31.25g, adding distil water 600ml, stir, be uniformly dispersed, then add calcium carbonate 20g, sucralose 15g and allured red pigment 0.3g while stirring, finally add PEO133.45g, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity C.
Add in dosing tank by serosity A, B and C, this dosing tank is made up of three parallel sulculuses, width is respectively 1.2,0.2,1.2cm, 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, 50 DEG C of dry 30min, due to solvent expansion effect, 3 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt knurling rolls embossing again, according to 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 obtained, thickness is 0.07mm, every sheet phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Daily 3 times.More than 12 years old children and adult one time 2 ~ 4; 6 ~ 12 years old children one time 1 ~ 2; 2 ~ 6 years old children one time 0.5 ~ 1.
This film preparation is made up of trichroism, aesthetic in appearance, becomes effervescent film, produce a large amount of bubble after meeting water, and stripping is rapid, and sense of taste is better.
Get this product 6, each clip becomes the thin film of 1cm × 1cm size, be the stainless steel silk folder of 2.0mm respectively with two-layer sieve aperture internal diameter, check according to the method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ A) under disintegration inspection technique tablet item, observe and record membrane and all to dissolve and by time of screen cloth.It is very fast that this product dissolves the time limit, is 48 ± 3s.
Get this product 6, clamp with paperclip respectively, adopt dissolution method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ C second methods) device, with 0.1M hydrochloric acid solution 500ml for dissolution medium, rotating speed is 50 turns per minute, from test sample contact dissolution medium, timing immediately, respectively through 1,2,3,5,10 and 15 minute time, get solution 1ml, filter, get subsequent filtrate, measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V D) and calculate the stripping quantity of every sheet.Its In Vitro Dissolution curve is shown in 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 all dissolve completely in 5min.
Embodiment 6
1) get codeine phosphate 50g, adding distil water 600ml, stir, be uniformly dispersed, add PEG40004g, citric acid 10g, saccharin sodium 5g, cyclamate 5g and titanium dioxide 10g more while stirring, finally add HPC116g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity A.
2) get PVP4.75g and HPMC20g, adding distil water 100ml, stir, be uniformly dispersed, then add PEG40001.65g, acesulfame potassium 4.95g and titanium dioxide 1.65g while stirring, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity B.
3) get promethazine hydrochloride 31.25g, adding distil water 600ml, stir, be uniformly dispersed, then add PEG40004g, sodium carbonate 10g, saccharin sodium 5g, cyclamate 5g and titanium dioxide 10g while stirring, finally add HPC134.75g, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity C.
Add in dosing tank by serosity A, B and C, this dosing tank is made up of three parallel sulculuses, width is respectively 1.2,0.2,1.2cm, 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, 70 DEG C of dry 20min, due to solvent expansion effect, 3 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt knurling rolls embossing again, according to 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 obtained, thickness is 0.08mm, every sheet phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Daily 3 times.More than 12 years old children and adult one time 2 ~ 4; 6 ~ 12 years old children one time 1 ~ 2; 2 ~ 6 years old children one time 0.5 ~ 1.
This film preparation is aesthetic in appearance, becomes effervescent film, produce a large amount of bubble after meeting water, and stripping is rapid, and sense of taste is better.
Get this product 6, each clip becomes the thin film of 1cm × 1cm size, be the stainless steel silk folder of 2.0mm respectively with two-layer sieve aperture internal diameter, check according to the method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ A) under disintegration inspection technique tablet item, observe and record membrane and all to dissolve and by time of screen cloth.It is very fast that this product dissolves the time limit, is 53 ± 4s.
Get this product 6, clamp with paperclip respectively, adopt dissolution method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ C second methods) device, with 0.1M hydrochloric acid solution 500ml for dissolution medium, rotating speed is 50 turns per minute, from test sample contact dissolution medium, timing immediately, respectively through 1,2,3,5,10 and 15 minute time, get solution 1ml, filter, get subsequent filtrate, measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V D) and calculate the stripping quantity of every sheet.Its In Vitro Dissolution curve is shown in 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 all dissolve completely in 5min.
Embodiment 7
1) get codeine phosphate 50g, adding distil water 600ml, stir, be uniformly dispersed, add xylitol 13g, aspartame 15g, light blue pigment 0.2g, tartaric acid 10g and vitamin E2 g more while stirring, finally add HPMC110g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity A.
2) get HPMC32.97g adding distil water 100ml, stir, then add light blue pigment 0.03g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity B.
3) promethazine hydrochloride 31.25g is got, adding distil water 600ml, stir, be uniformly dispersed, then add xylitol 13g, aspartame 15g, light blue pigment 0.2g, sodium carbonate 10g and vitamin E2 g while stirring, finally add HPMC128.75g, stir, cross 80 mesh sieves, removing insoluble matter, vacuum defoamation.Obtain serosity C.
Add in dosing tank by serosity A, B, C, this dosing tank is made up 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 coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 70 DEG C of dry 20min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt knurling rolls embossing again, according to 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 obtained, thickness is 0.08mm, every sheet phosphoric acid codeine 5mg, promethazine hydrochloride 3.125mg.Daily 3 times.More than 12 years old children and adult one time 2 ~ 4; 6 ~ 12 years old children one time 1 ~ 2; 2 ~ 6 years old children one time 0.5 ~ 1.
This medicine film preparation is aesthetic in appearance.Become effervescent film after meeting water, produce a large amount of bubble, stripping is rapid, and sense of taste is better.
Get this product 6, each clip becomes the thin film of 1cm × 1cm size, be the stainless steel silk folder of 2.0mm respectively with two-layer sieve aperture internal diameter, check according to the method (Chinese Pharmacopoeia version in 2010 two annex Ⅹ A) under disintegration inspection technique tablet item, observe and record membrane and all to dissolve and by time of screen cloth.It is very fast that this product dissolves the time limit, is 55 ± 4s.
Claims (6)
1. codeine phosphate and promethazine hydrochloride compound recipe film-like preparation, is characterized in that, comprises codeine phosphate and the promethazine hydrochloride of strip film strips and load treatment effective dose thereon;
Described strip film strips, comprises acidic strip film strips and alkaline strip film strips, and described acidic strip film strips and alkaline strip film strips are connected, and spaced setting;
Described acidic strip film strips, based on highly-water-soluble macromolecule filming material, with film strips weighing scale, containing the acidizer of 1 ~ 20%;
Described alkaline strip film strips, based on highly-water-soluble macromolecule filming material, with film strips weighing scale, containing the alkaline agent of 1 ~ 20%;
One in described codeine phosphate or promethazine hydrochloride respectively load in acidic strip film strips or alkaline strip film strips;
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;
Preparation method, comprises the steps:
(1) codeine phosphate or promethazine hydrochloride, acidizer and other adjuvants are mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained acid serosity A;
(2) codeine phosphate or promethazine hydrochloride, alkaline agent and other adjuvants are mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained alkaline slurry B;
When step (1) adopts codeine phosphate, then step (2) adopts promethazine hydrochloride;
When step (1) adopts promethazine hydrochloride, then step (2) adopts codeine phosphate;
(3) serosity A and serosity B successively interval is coated on flat board, due to solvent expansion effect, is complex as a whole, obtain medicine carrying thin film;
(4) by the medicine carrying thin film that step (3) obtains, dry 5 ~ 30min at the temperature of 50 ~ 90 DEG C, the film-like preparation described in acquisition.
2. codeine phosphate according to claim 1 and promethazine hydrochloride compound recipe film-like preparation, it is characterized in that, described acidic strip film strips comprises the component of following percentage by weight:
Described alkaline strip film strips comprises the component of following percentage by weight:
With the total weight of described film-like preparation, described codeine phosphate or the content of promethazine hydrochloride are 1 ~ 30%, and the weight ratio of codeine phosphate and promethazine hydrochloride is: codeine phosphate: promethazine hydrochloride=1: 0.625.
3. codeine phosphate according to claim 1 and promethazine hydrochloride compound recipe film-like preparation, it is characterized in that, described acidic strip film strips comprises the component of following percentage by weight:
Described alkaline strip film strips comprises the component of following percentage by weight:
With the total weight of described film-like preparation, described codeine phosphate or the content of promethazine hydrochloride are 5 ~ 15%.
4. codeine phosphate and promethazine hydrochloride compound recipe film-like preparation, is characterized in that, comprises codeine phosphate and the promethazine hydrochloride of strip film strips and load treatment effective dose thereon;
Described strip film strips comprises blank tape, acidic strip film strips and alkaline strip film strips, described blank tape of establishing is put between described acidic strip film strips and alkaline strip film strips, and be connected with described acidic strip film strips and alkaline strip film strips respectively, described blank tape comprises highly-water-soluble macromolecule filming material;
Described acidic strip film strips, based on highly-water-soluble macromolecule filming material, with film strips weighing scale, containing the acidizer of 1 ~ 20%;
Described alkaline strip film strips, based on highly-water-soluble macromolecule filming material, with film strips weighing scale, containing the alkaline agent of 1 ~ 20%;
One in described codeine phosphate or promethazine hydrochloride respectively load in acidic strip film strips or alkaline strip film strips;
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;
Preparation method, comprises the steps:
(1) codeine phosphate or promethazine hydrochloride, acidizer and other adjuvants are mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained acid serosity A;
(2) codeine phosphate or promethazine hydrochloride, alkaline agent and other adjuvants are mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained alkaline slurry B;
When step (1) adopts codeine phosphate, then step (2) adopts promethazine hydrochloride;
When step (1) adopts promethazine hydrochloride, then step (2) adopts codeine phosphate;
(3) other adjuvants are mixed with water, obtain the water slip that weight concentration is 15 ~ 35%, obtained blank serosity C;
(4) serosity A, serosity B and blank serosity C are coated on flat board in interval successively, due to solvent expansion effect, are complex as a whole, obtain medicine carrying thin film;
(5) by the medicine carrying thin film that step (4) obtains, dry 5 ~ 30min at the temperature of 50 ~ 90 DEG C, the composite film preparation described in acquisition.
5. codeine phosphate according to claim 4 and promethazine hydrochloride compound recipe film-like preparation, it is characterized in that, described acidic strip film strips comprises the component of following percentage by weight:
Described alkaline strip film strips comprises the component of following percentage by weight:
Described blank tape comprises the component of following percentage by weight:
With the total weight of described film-like preparation, described codeine phosphate or the content of promethazine hydrochloride are 1 ~ 30%, and the weight ratio of codeine phosphate and promethazine hydrochloride is: codeine phosphate: promethazine hydrochloride=1: 0.625.
6. the codeine phosphate according to any one of Claims 1 to 5 and promethazine hydrochloride compound recipe film-like preparation, it is characterized in that, described water soluble polymer filmogen comprise in polyvinyl alcohol, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, sodium alginate, CMC-Na, polyoxyethylene, Bletilla glucomannan, maltodextrin, corn starch or carrageenan more than one.
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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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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1658835A (en) * | 2002-06-04 | 2005-08-24 | Lts罗曼治疗方法有限公司 | Film-shaped, dissolvable preparations for active substance release and method for the production thereof |
| 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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