CN103222977A - Granisetron and dexamethasone compound transdermal controlled-release patch and preparation method thereof - Google Patents
Granisetron and dexamethasone compound transdermal controlled-release patch and preparation method thereof Download PDFInfo
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- CN103222977A CN103222977A CN2013101939347A CN201310193934A CN103222977A CN 103222977 A CN103222977 A CN 103222977A CN 2013101939347 A CN2013101939347 A CN 2013101939347A CN 201310193934 A CN201310193934 A CN 201310193934A CN 103222977 A CN103222977 A CN 103222977A
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- sensitive adhesive
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- granisetron
- dexamethasone
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- 238000002360 preparation method Methods 0.000 title claims abstract description 23
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- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims abstract description 39
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the field of pharmaceutical preparations, in particular to a granisetron and dexamethasone compound transdermal controlled release patch and a preparation method thereof. The patch is characterized by consisting of a back lining layer, a pressure-sensitive adhesive skeleton type drug-containing storage layer and a protective film, wherein the pressure-sensitive adhesive skeleton type drug-containing storage layer contains granisetron, dexamethasone, a transdermal penetration enhancer, a cross-linking agent, a plasticizer and pressure-sensitive adhesive, the transdermal penetration enhancer is preferably azone, and the content of azone is 2-5% by weight based on the total weight of the pressure-sensitive adhesive skeleton type drug-containing storage layer. The invention overcomes the defect of unstable permeation quantity caused by large difference of oil-water distribution coefficients of granisetron and dexamethasone, and simultaneously leads two medicaments of granisetron and dexamethasone with different physicochemical properties to have higher permeation quantity and maintain higher blood concentration in a longer time.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of compound control-released percutaneous patch for the treatment of the nausea and vomiting due to chemotherapy, radiotherapy or the postoperative and preparation method thereof.
Background technology
Granisetron (Granisetron) chemistry 1-methyl-N-(9-methyl-9-azabicyclic [3,3,1] nonane-3-yl) by name-1H-indole-3-Methanamide, molecular formula is C
18H
24N
4O is white crystalline powder, and granisetron is a kind of potent high selectivity 5-HT
3Receptor antagonist, its resisting emesis mechanism are highly selectively to hinder abdominal part vagus nerve end neuron, and the 5-HT on ventriculus quartus's emetic receptive field of chemistry and the intestinal mucosa enterochromaffin cell
3Receptor.Granisetron and the structural 5-HT of adjusting vomiting
3Receptor binding site has high-affinity and high selectivity.
Dexamethasone (Dexamethasone) chemical name 16 Alpha-Methyls-11 β, 17 α, 21-trihydroxy-9 α-fuprednate-1,4-diene-3, the 20-diketone, molecular formula is C
22H
29FO
5, be white or almost white crystalline powder; Odorless.Dexamethasone is the same with other glucocorticoids, has pharmacological actions such as antiinflammatory, antiendotoxin, inhibition immunity, shock and enhancing stress, so be widely used in treating multiple disease, as autoimmune disease, allergy, inflammation, asthma and department of dermatologry, ophthalmic diseases.The Decameth indispensable first-aid medicine that gives emergency treatment to a dying patient especially, in recent ten years, the clinicist uses dexamethasone sodium phosphate prevention and treats drug allergy that all kinds of Chinese medicine and western medicine cause and diseases such as fever that the treatment viral influenza causes, and dexamethasone clinical application amount is increased year by year.
Drug combination (Drug combination) is meant two or more medicine while of adopting in order to reach therapeutic purposes or successively uses.Nausea and vomiting Drug therapy had the strategy of single drug and drug combination substantially in the past.Even single drug treatment nausea and vomiting only often has still less patient's nausea and vomiting of may command 30%-60%, to the acute vomiting weak effect; The bad increase dosage of effect, curative effect increases few, and side effect can increase by the logarithm level; Generally only act on an acceptor site and can not reach shortcomings such as effective therapeutic effect.And drug combination has the different medicine nausea of mechanism of action and the vomiting interaction energy adds up, collaborative or complementary, can effectively improve the control rate of nausea and vomiting than the folk prescription medication; Dosage increased the ill effect that causes when low dose of drug combination can reduce single drug; And can limit advantages such as another side effects of pharmaceutical drugs mutually with medicine.So drug combination has become the main application method of the nausea and vomiting due to treatment chemotherapy, radiotherapy or the postoperative.Granisetron and dexamethasone drug combination have obtained the consistent of doctor and patient as the effective ways of the nausea and vomiting due to treatment chemotherapy, radiotherapy or the postoperative and have admitted, and extensively apply to clinical, it is advantageous that synergism by two medicines, improve the control rate of nausea and vomiting effectively, and the minimizing using dosage reduces toxic and side effects.
Transdermal drug delivery system (Transdermal drug delivery system, TTDS) percutaneous drug administration preparation is since 1970's, and oneself becomes a research focus in the pharmaceutics field.With conventional medication relatively, it has outstanding feature: 1. improve compliance of patients, needn't frequent drug administration, particularly therapeutic regimen is unfamiliar with or remember the gerontal patient who is forbidden, particular importance seems; 2. directly enter the body circulation after the medicine percutaneous absorbs, drug absorption is not influenced at complicated factors such as intestinal traveling times by the interior pH of digestive tract, food and medicine; Avoid gastrointestinal tract to the destruction of medicine and the first pass effect of liver, reduce the individual difference of medication; 3. percutaneous dosing long action time, slow release effect is obvious, reduces administration number of times, prolongs dosing interval; 4. blood drug level is steady, avoids the appearance that drug level is too high and concentration is crossed low phenomenon, reduces toxic and side effects; 5. percutaneous dosing is the non-invasive administration, can not cause the damage of human body; 6. agents area is at body surface, and interruption of the administration is convenient, improves safety, reduces the danger of oral administration or drug administration by injection.
Though transdermal drug delivery system has many advantages, skin is still most drug and is difficult to penetrating barrier together, and after many drug transdermal administrations, penetrating speed does not reach the treatment requirement, thereby can not guarantee that the skin permeation of drugs of q.s enters in the body.Granisetron profit partition coefficient is 0.78, very easily water-soluble, dexamethasone profit partition coefficient is 3.92, be fat-soluble compound, there is certain diversity in two property of medicine matter, and self-dependent transdermal ability does not reach the treatment requirement, the approach that must seek suitable promotion drug absorption can increase both percutaneous absorption rates simultaneously, just can reach curative effect.Therefore the compound transdermal patch for preparing both has certain technical difficulty.
Summary of the invention
The invention discloses the compound control-released percutaneous patch of a kind of granisetron and dexamethasone, by selecting suitable transdermal penetrating agent, overcome granisetron and dexamethasone profit partition coefficient difference causes the unsettled defective of infiltration capacity greatly, allowed physicochemical property different granisetron and two kinds of medicines of dexamethasone higher infiltration capacity be arranged and in the long time, keep higher blood drug level simultaneously.
Patch of the present invention is made up of backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film; wherein pressure-sensitive adhesive matrix type pastille storage layer contains granisetron, dexamethasone, transdermal penetrating agent, cross-linking agent, plasticizer and pressure sensitive adhesive; the preferred azone of transdermal enhancer; and the content in pressure-sensitive adhesive matrix type pastille storage layer gross weight azone is 2%-5%, is weight percentage.
The parts by weight of each component are preferred in the above-mentioned pressure-sensitive adhesive matrix type pastille storage layer: 5～20 parts of compound medicines, 2～4 parts of azones, 5～15 parts of cross-linking agent, 10～30 parts of plasticizers, 30～50 parts of pressure sensitive adhesives.
Preferred 1:1～the 1:10 of the weight ratio of granisetron and dexamethasone.More preferably 3:8.
The preferred dibutyl sebacate of plasticizer, PEG400 or citric acid triethyl; The preferred succinic acid of cross-linking agent, citric acid or tartaric acid; The preferred macromolecular material polyacrylic resin of pressure sensitive adhesive.
The preferred 0.5-2.5mm of pressure-sensitive adhesive matrix type pastille storage layer thickness.
Described backing layer preferably constitutes with the macromolecular material that a kind of shipwreck in aluminium foil composite polyethylene film, polychloroethylene film, nylon resin film, cellulose acetate membrane, poly tetrafluoroethylene, polypropylene type non-woven fabrics or the Du Pont's non-woven fabrics is soaked into, and its thickness is 0.02-0.3mm.
Described protecting film adopt separate paper, aluminium foil or aluminum-plastic composite membrane one of them.
As need better control drug release speed and first medication reach required blood drug level rapidly, can between pressure-sensitive adhesive matrix type pastille storage layer and protecting film, add speed release-controlled film and rapid release pastille pressure-sensitive adhesive layer successively.
Described speed release-controlled film adopts ethylene/vinyl acetate copolymer a kind of of high density or low-density polyethylene film or improvement, the preferred 0.02-0.3mm of its thickness.
Described rapid release pastille pressure-sensitive adhesive layer selects for use polyacrylate to make the 1-10% compound medicine of pressure sensitive adhesive material and the mass ratio that accounts for the pressure sensitive adhesive material and the 2-20% transdermal penetrating agent that accounts for the mass ratio of pressure sensitive adhesive material is formed the preferred 0.05-0.5mm of its thickness.
Compound control-released percutaneous patch of the present invention can prepare with following method:
(1) granisetron, dexamethasone and cross-linking agent are dissolved in the dehydrated alcohol, are stirred to dissolving, slowly drip plasticizer, be stirred to clear and bright solution and add pressure sensitive adhesive again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose;
(2) this pastille pressure sensitive adhesive bank glue is coated on the backing film with coating machine, become the uniform thin film of thickness;
(3) this thin film is sent into the air dry oven drying, form super saturated solid solution system transparent membrane after this coating liquid drying;
(4) above-mentioned thin film is pressed protective layer, promptly.
The inventor is in early-stage Study, in order to overcome granisetron and dexamethasone profit partition coefficient difference causes defectives such as infiltration capacity instability greatly, adopted multiple transdermal penetrating agent to test, found that, when selecting 2～5% azones as the transdermal penetrating agent, short saturating effect is better, and low concentration can be brought into play bigger transdermal enhancing effect.Be the result of the test that adopts the short penetrating agent of some different transdermals below:
Adopt general preparation patch technology, pressure-sensitive adhesive matrix type pastille storage layer contains the composition of granisetron, dexamethasone, cross-linking agent, plasticizer and pressure sensitive adhesive and measures constant, what change is the transdermal penetrating agent, also prepare a compound recipe patch that does not add any penetrating agent, prepare compound transdermal patch as stated above.
Transdermal test in vitro diffusion experiment of the present invention adopts the single chamber Franz diffusion cell of improvement.This device is involuted by two cup-shaped grournd glass container assemblies up and down, and skin is clipped in the middle, and is fixed with the rustless steel clamping.Drug release hole diameter 1.5cm, release area are 1.77cm
2, receiving chamber's volume is 17mL.The medium of accepting of granisetron and dexamethasone is 40% ethanol-normal saline solution.
The mouse skin of handling well is fixed between two Room of intelligent transdermal tester diffusion cell, stratum corneum side is to supply chamber, the patch and the contrast patch that do not contain or contain different transdermal penetrating agents are attached on the skin keratin aspect, make it to contact closely, and be fixed on supply chamber with skin.Reception liquid is 40% ethanol-normal saline solution.Set water bath with thermostatic control (32 ± 0.1) ° C, 300rmin
-1Magnetic agitation.Respectively at 1,2,4,6,8,10,12,24,36, the 48h 2mL that takes a sample replenishes barren 40% ethanol of 2mL-normal saline solution simultaneously.Sample is measured peak area, substitution standard curve Equation for Calculating drug level through the HPLC method.
Different penetrating agents to granisetron and dexamethasone compound recipe patch 48h in-vitro percutaneous short ooze the effect concrete outcome see Table 1 and table 2(n=5)
Granisetron transdermal penetration speed under the effect of the different transdermal penetrating agent of table 1
| Penetrating agent | The transdermal equation | r | Js（μg·cm -2·h -1） | The anatonosis ratio |
| No penetrating agent | Q=5.5096t-5.5653 | 0.9965 | 5.5096 | 1 |
| 1% azone | Q=15.265t-33.537 | 0.9974 | 15.265 | 2.77 |
| 2% azone | Q=17.849t–37.894 | 0.9982 | 17.849 | 3.24 |
| 3% azone | Q=19.635t-43.98 | 0.9979 | 19.635 | 3.56 |
| 5% azone | Q=20.892t-8.5918 | 0.9982 | 20.892 | 3.79 |
| 7% azone | Q=15.783t–36.908 | 0.9932 | 15.783 | 2.86 |
| 5% oleic acid | Q=8.0308t-31.124 | 0.9903 | 8.0308 | 1.46 |
| 5% isopropyl myristate | Q=5.1714t-9.0587 | 0.998 | 5.1714 | 0.94 |
| 3% decyl methyl sulfoxide | Q=6.3175t–10.735 | 0.9947 | 6.3175 | 1.15 |
| 5% tween 80 | Q=7.8906t–9.5748 | 0.9993 | 7.8906 | 1.43 |
| 10% propylene glycol | Q=11.264t–10.967 | 0.9921 | 11.264 | 2.04 |
Dexamethasone transdermal penetration speed under the effect of the different transdermal penetrating agent of table 2
| Penetrating agent | The transdermal equation | r | Js（μg·cm -2·h -1） | The anatonosis ratio |
| No penetrating agent | Q=6.1038t–13.575 | 0.9975 | 6.1038 | 1 |
| 1% azone | Q=12.285t–30.593 | 0.9981 | 12.285 | 2.01 |
| 2% azone | Q=12.738t–19.048 | 0.9943 | 12.738 | 2.09 |
| 3% azone | Q=13.046t–12.983 | 0.9956 | 13.046 | 2.14 |
| 5% azone | Q=14.275t–22.754 | 0.9962 | 14.275 | 2.39 |
| 7% azone | Q=12.135t–27.563 | 0.9953 | 12.135 | 1.99 |
| 5% oleic acid | Q=5.7028t–26.743 | 0.9879 | 5.7028 | 0.93 |
| 5% isopropyl myristate | Q=8.233t–9.0528 | 0.9978 | 8.233 | 1.35 |
| 3% decyl methyl sulfoxide | Q=7.3713t–11.748 | 0.9992 | 7.3713 | 1.21 |
| 5% tween 80 | Q=8.9360t–15.456 | 0.9905 | 8.9360 | 1.46 |
| 10% propylene glycol | Q=9.4732t–13.783 | 0.9988 | 9.4732 | 1.55 |
By table 1 and table 2 as seen, in the selected penetrating agent of experiment, oleic acid does not have transdermal enhancing effect substantially to dexamethasone, but granisetron is had certain facilitation.5% isopropyl myristate and 3% decyl methyl sulfoxide are not obvious to two medicines the short effect of oozing, and 5% tween 80 and 10% propylene glycol have certain short effect of oozing to two medicines.Azone all has the bigger short effect of oozing to two medicines, and azone does not have concentration dependent to the short effect of dexamethasone, and the short saturating effect of various concentration is all better.Then along with the increase of concentration, short saturating effect increases to granisetron.All things considered, azone is all better to the short effect of two medicines, and low concentration can be brought into play the bigger short effect of oozing.The short saturating concentration of the best of azone is 2～5%, and improving azone concentration again can not reinforced effects.
Description of drawings
Fig. 1 is the compound transdermal patche (wherein 1 is backing film, the 2nd, pressure-sensitive adhesive matrix pastille storage layer the 2, the 5th, protecting film) that embodiment 1～7 makes
Fig. 2 is the compound transdermal patche (wherein 1 is backing film, the 2nd, pressure-sensitive adhesive matrix pastille storage layer, the 3rd, speed release-controlled film, the 4th, rapid release pastille pressure-sensitive adhesive layer, the 5th, protecting film) that embodiment 8 makes
Fig. 3 is the release in vitro curve of granisetron in granisetron-dexamethasone compound transdermal patch
Fig. 4 is the release in vitro curve of dexamethasone in granisetron-dexamethasone compound transdermal patch
The specific embodiment
The compound control-released percutaneous patch of preparation granisetron-dexamethasone is made up of backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film, and its preparation method is:
(1) precision takes by weighing the 0.18g granisetron, 0.48g dexamethasone, 0.15g succinic acid, add 6ml ethanol and be stirred to dissolving, slow adding 1g dibutyl sebacate and 0.16g azone are stirred to clear and bright solution and add 1.8g Eudragit E100 again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose;
(2) above-mentioned pastille pressure sensitive adhesive bank viscose is heated to the pastille glue that the ethanol volatilization obtains suitable denseness, ultrasonic degas adopts curtain coating technology to be coated on the CoTran of certain area
TMOn the 9720 polyethylene backing films, put into 60 ° of C of baking oven and solidify 40min, the superimposed inertia silication separate paper in cooling back promptly.Its structure is seen Fig. 1.
One, the mensuration of compound recipe patch viscous force
Adopt the spin slope to stop method and measure embodiment 1 compound recipe patch viscous force just.Suitable serial steel ball is rolled across the stickiness face that lies on the hang plate respectively,, estimate its size of viscous force just according to the biggest ball steel ball that the stickiness face of test sample can cling.Measure 3 batches by the homemade sample of above-mentioned prescription, experimental result sees Table 3.
Patch is pasted on the bread board surface.The vertical placement hung the counterweight of a definite quality along the length direction of patch, and the slippage of record patch is until time that comes off or the distance that moves down within a certain period of time.Measure 3 batches of homemade samples, experimental result sees Table 4.
Table 3 compound transdermal patch is the mensuration of viscous force just
| |
1 | 2 | 3 |
| First viscous force (steel ball number) | 8 | 8 | 8 |
The mensuration that table 4 compound transdermal patch is held viscous force
| |
1 | 2 | 3 |
| Hold viscous force (min) | 28 | 26 | 29 |
The result judges: in the steel ball that 3 test samples stick separately, if 3 all be maximum steel ball ball number, perhaps two be the steel ball ball number of maximum, and another steel ball ball is number only little No. one, and then the result number represents with the steel ball ball of maximum; If one is maximum steel ball ball number, and two steel ball balls are number only little No. one in addition, and then the result is with number expression of only little No. one steel ball ball.
Make the compound recipe patch have good first viscous force by prescription of the present invention and production technology as can be known and hold viscous force by table 3 and table 4.
Two, patch release in vitro degree test
Transdermal patch by backing layer, the drug depot, adhesive layer of (or do not have) release-controlled film arranged and form with the protective layer that preceding need are removed.The pharmaceutically-active time is by the medicament contg and the rate of releasing drug decision of transdermal patch.
Release medium is added in the stripping rotor, and pre-temperature is to 32 ± 0.5 ° of C; Embodiment 1 transdermal patch is fixed on the centre of net dish, and emission surface upwards places the stripping rotor bottom with the net dish, and making patch parallel with the surfaces of revolution at the bottom of the oar, the distance of adjusting between stirring paddle and the net dish is 25 ± 2mm, begins to stir and timing (10min, 20min, 40min, 60min, 90min, 150min, 210min, 300min, 360min) sampling 2ml, and in time replenish the equal-volume blank medium.The HPLC method is measured concentration and is calculated release.
The release in vitro curve of granisetron and dexamethasone as shown in Figure 3 and Figure 4 in granisetron-dexamethasone compound transdermal patch.Can obtain from the measurement result of release, granisetron release when 90min reaches 90% in granisetron-dexamethasone compound transdermal patch, dexamethasone then when 150min release reach 90%.
The compound control-released percutaneous patch of preparation granisetron-dexamethasone is made up of backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film, and its preparation method is:
(1) precision takes by weighing the 0.18g granisetron, 0.48g dexamethasone, 0.15g succinic acid, add 6ml ethanol and be stirred to dissolving, slow adding 1g PEG400 and 0.16g azone are stirred to clear and bright solution and add 1.8g Eudragit E100 again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose;
(2) above-mentioned pastille pressure sensitive adhesive bank viscose is heated to the pastille glue that the ethanol volatilization obtains suitable denseness, ultrasonic degas adopts curtain coating technology to be coated on the CoTran of certain area
TMOn the 9720 polyethylene backing films, put into 60 ° of C of baking oven and solidify 40min, the superimposed inertia silication separate paper in cooling back promptly.
Embodiment 3
The compound control-released percutaneous patch of preparation granisetron-dexamethasone is made up of backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film, and its preparation method is:
(1) precision takes by weighing the 0.18g granisetron, 0.48g dexamethasone, 0.16g citric acid, add 6ml ethanol and be stirred to dissolving, slow adding 1g dibutyl sebacate and 0.16g azone are stirred to clear and bright solution and add 1.8g Eudragit E100 again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose; (2) above-mentioned pastille pressure sensitive adhesive bank viscose is heated to the pastille glue that the ethanol volatilization obtains suitable denseness, ultrasonic degas adopts curtain coating technology to be coated on the CoTran of certain area
TMOn the 9720 polyethylene backing films, put into 60 ° of C of baking oven and solidify 40min, the superimposed inertia silication separate paper in cooling back promptly.
Embodiment 4
The compound control-released percutaneous patch of preparation granisetron-dexamethasone is made up of backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film, and its preparation method is:
(1) precision takes by weighing the 0.18g granisetron, 0.48g dexamethasone, 0.13g tartaric acid, add 6ml ethanol and be stirred to dissolving, slow adding 1g dibutyl sebacate and 0.16g azone are stirred to clear and bright solution and add 1.8g Eudragit E100 again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose;
(2) above-mentioned pastille pressure sensitive adhesive bank viscose is heated to the pastille glue that the ethanol volatilization obtains suitable denseness, ultrasonic degas adopts curtain coating technology to be coated on the CoTran of certain area
TMOn the 9720 polyethylene backing films, put into 60 ° of C of baking oven and solidify 40min, the superimposed inertia silication separate paper in cooling back promptly.
Embodiment 5
The compound control-released percutaneous patch of preparation granisetron-dexamethasone is made up of backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film, and its preparation method is:
(1) precision takes by weighing the 0.18g granisetron, 0.48g dexamethasone, 0.13g tartaric acid, add 6ml ethanol and be stirred to dissolving, slow adding 0.9g PEG400 and 0.16g azone are stirred to clear and bright solution and add 1.8g Eudragit E100 again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose;
(2) above-mentioned pastille pressure sensitive adhesive bank viscose is heated to the pastille glue that the ethanol volatilization obtains suitable denseness, ultrasonic degas adopts curtain coating technology to be coated on the CoTran of certain area
TMOn the 9720 polyethylene backing films, put into 60 ° of C of baking oven and solidify 40min, the superimposed inertia silication separate paper in cooling back promptly.
Embodiment 6
The compound control-released percutaneous patch of preparation granisetron-dexamethasone is made up of backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film, and its preparation method is:
(1) precision takes by weighing the 0.18g granisetron, 0.48g dexamethasone, 0.16g citric acid, add 6ml ethanol and be stirred to dissolving, slow adding 1g PEG400 and 0.16g azone are stirred to clear and bright solution and add 1.8g Eudragit E100 again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose;
(2) above-mentioned pastille pressure sensitive adhesive bank viscose is heated to the pastille glue that the ethanol volatilization obtains suitable denseness, ultrasonic degas adopts curtain coating technology to be coated on the CoTran of certain area
TMOn the 9720 polyethylene backing films, put into 60 ° of C of baking oven and solidify 40min, the superimposed inertia silication separate paper in cooling back promptly.
Embodiment 7
The compound control-released percutaneous patch of preparation granisetron-dexamethasone is made up of backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film, and its preparation method is:
(1) precision takes by weighing the 0.18g granisetron, 0.48g dexamethasone, 0.15g citric acid, add 6ml ethanol and be stirred to dissolving, slow adding 1g citric acid triethyl and 0.16g azone are stirred to clear and bright solution and add 1.8g Eudragit E100 again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose;
(2) above-mentioned pastille pressure sensitive adhesive bank viscose is heated to the pastille glue that the ethanol volatilization obtains suitable denseness, ultrasonic degas adopts curtain coating technology to be coated on the CoTran of certain area
TMOn the 9720 polyethylene backing films, put into 60 ° of C of baking oven and solidify 40min, the superimposed inertia silication separate paper in cooling back promptly.
Embodiment 8
The compound control-released percutaneous patch of preparation granisetron-dexamethasone is made up of backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film, and its preparation method is:
(1) precision takes by weighing the 0.18g granisetron, 0.48g dexamethasone, 0.15g citric acid, add 6ml ethanol and be stirred to dissolving, slow adding 1g citric acid triethyl and 0.16g azone are stirred to clear and bright solution and add 1.8g Eudragit E100 again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose;
(2) precision takes by weighing the 0.09g granisetron, and the 0.24g dexamethasone adds 3ml ethanol and is stirred to dissolving, slowly adds the 0.07g azone and is stirred to transparent gluey rapid release pastille pressure-sensitive adhesive layer glue;
(2) above-mentioned pastille pressure sensitive adhesive bank viscose is heated to the pastille glue that the ethanol volatilization obtains suitable denseness, ultrasonic degas adopts curtain coating technology to be coated on the CoTran of certain area
TMOn the 9720 polyethylene backing films, the polyethylene film that superposes successively in the above, and with curtain coating technology rapid release pastille pressure-sensitive adhesive layer glue is uniformly coated on above the polyethylene film, to put into 60 ° of C of baking oven and solidify 40min, the superimposed inertia silication separate paper in cooling back is promptly.Its structure is seen Fig. 2.
Claims (9)
1. compound control-released percutaneous patch that contains granisetron and dexamethasone; form by backing layer, pressure-sensitive adhesive matrix type pastille storage layer and protecting film; wherein pressure-sensitive adhesive matrix type pastille storage layer contains granisetron, dexamethasone, transdermal penetrating agent, cross-linking agent, plasticizer and pressure sensitive adhesive; it is characterized in that: transdermal enhancer is an azone; and the content in pressure-sensitive adhesive matrix type pastille storage layer gross weight azone is 2%-5%, is weight percentage.
2. the compound control-released percutaneous patch of claim 1, wherein the parts by weight of each component are in the pressure-sensitive adhesive matrix type pastille storage layer: 5～20 parts of compound medicines, 2～4 parts of azones, 5～15 parts of cross-linking agent, 10～30 parts of plasticizers, 30～50 parts of pressure sensitive adhesives.
3. the compound control-released percutaneous patch of claim 1, wherein the weight ratio of granisetron and dexamethasone is 1:1～1:10.
4. the compound control-released percutaneous patch of claim 1, wherein plasticizer is dibutyl sebacate, PEG400 or citric acid triethyl; Cross-linking agent is succinic acid, citric acid or tartaric acid; Pressure sensitive adhesive is a polyacrylic resin.
5. the compound control-released percutaneous patch of claim 1, wherein pressure-sensitive adhesive matrix type pastille storage layer thickness is 0.5-2.5mm.
6. the compound control-released percutaneous patch of claim 1, folded successively between described pressure-sensitive adhesive matrix pastille storage layer and protecting film have speed release-controlled film and a rapid release pastille pressure-sensitive adhesive layer.
7. the compound control-released percutaneous patch of claim 6, the speed release-controlled film is made up of polyethylene film or ethylene/vinyl acetate copolymer.
8. the compound control-released percutaneous patch of claim 7, rapid release pastille pressure-sensitive adhesive layer is made up of polyacrylate, compound medicine and transdermal penetrating agent.
9. the preparation method of the compound control-released percutaneous patch of claim 1 comprises:
(1) granisetron, dexamethasone and cross-linking agent are dissolved in the dehydrated alcohol, are stirred to dissolving, slowly drip plasticizer and azone, be stirred to clear and bright solution and add pressure sensitive adhesive again, continue to be stirred to transparent gluey pastille pressure sensitive adhesive bank viscose;
(2) pastille pressure sensitive adhesive bank glue is coated on the backing film with coating machine, become the uniform thin film of thickness;
(3) thin film is sent into the air dry oven drying, formed super saturated solid solution system transparent membrane after this coating liquid drying;
(4) above-mentioned thin film is pressed protective layer, promptly.
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| CN2013101939347A CN103222977A (en) | 2013-05-22 | 2013-05-22 | Granisetron and dexamethasone compound transdermal controlled-release patch and preparation method thereof |
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| CN2013101939347A CN103222977A (en) | 2013-05-22 | 2013-05-22 | Granisetron and dexamethasone compound transdermal controlled-release patch and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105147642A (en) * | 2015-07-31 | 2015-12-16 | 大连理工大学 | Transdermal patch containing formoterol or fumarate thereof |
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| CN101721394A (en) * | 2008-10-29 | 2010-06-09 | 大连理工大学 | Granisetron and/or hydrochloride patch thereof |
| CN102283820A (en) * | 2011-08-02 | 2011-12-21 | 沈阳药科大学 | Granisetron transdermal patch and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105147642A (en) * | 2015-07-31 | 2015-12-16 | 大连理工大学 | Transdermal patch containing formoterol or fumarate thereof |
| CN105147642B (en) * | 2015-07-31 | 2018-02-16 | 大连理工大学 | A kind of transdermal patch containing Formoterol or its fumarate |
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