CN117159508A - Hot-melt patch and preparation method thereof - Google Patents
Hot-melt patch and preparation method thereof Download PDFInfo
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- CN117159508A CN117159508A CN202311201211.7A CN202311201211A CN117159508A CN 117159508 A CN117159508 A CN 117159508A CN 202311201211 A CN202311201211 A CN 202311201211A CN 117159508 A CN117159508 A CN 117159508A
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- Prior art keywords
- styrene
- hot
- melt
- isoprene
- patch
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- 239000012943 hotmelt Substances 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title description 13
- 229920000346 polystyrene-polyisoprene block-polystyrene Polymers 0.000 claims abstract description 29
- 239000011241 protective layer Substances 0.000 claims abstract description 19
- 229920002367 Polyisobutene Polymers 0.000 claims abstract description 16
- 239000004014 plasticizer Substances 0.000 claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- 239000010410 layer Substances 0.000 claims abstract description 13
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 claims abstract description 12
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims abstract description 12
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims abstract description 11
- 239000012790 adhesive layer Substances 0.000 claims abstract description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 16
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 claims description 15
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 claims description 15
- 229960002373 loxoprofen Drugs 0.000 claims description 15
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 claims description 15
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 14
- 239000003381 stabilizer Substances 0.000 claims description 14
- 229960002390 flurbiprofen Drugs 0.000 claims description 13
- 229940057995 liquid paraffin Drugs 0.000 claims description 13
- 125000005456 glyceride group Chemical group 0.000 claims description 11
- 239000000377 silicon dioxide Substances 0.000 claims description 11
- 235000012239 silicon dioxide Nutrition 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 239000003963 antioxidant agent Substances 0.000 claims description 8
- 239000011248 coating agent Substances 0.000 claims description 8
- 238000000576 coating method Methods 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- 230000003078 antioxidant effect Effects 0.000 claims description 7
- 239000006184 cosolvent Substances 0.000 claims description 7
- 239000002085 irritant Substances 0.000 claims description 7
- 239000003961 penetration enhancing agent Substances 0.000 claims description 7
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 6
- 238000002844 melting Methods 0.000 claims description 6
- 230000008018 melting Effects 0.000 claims description 6
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 4
- 229960000991 ketoprofen Drugs 0.000 claims description 4
- 235000019483 Peanut oil Nutrition 0.000 claims description 3
- 229960001259 diclofenac Drugs 0.000 claims description 3
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 3
- 229960000905 indomethacin Drugs 0.000 claims description 3
- 239000000155 melt Substances 0.000 claims description 3
- 239000004006 olive oil Substances 0.000 claims description 3
- 235000008390 olive oil Nutrition 0.000 claims description 3
- 239000000312 peanut oil Substances 0.000 claims description 3
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 2
- 239000004831 Hot glue Substances 0.000 claims 1
- 230000001070 adhesive effect Effects 0.000 abstract description 21
- 239000011159 matrix material Substances 0.000 abstract description 6
- 239000003292 glue Substances 0.000 abstract description 4
- 230000000052 comparative effect Effects 0.000 description 24
- 239000000853 adhesive Substances 0.000 description 19
- 238000004090 dissolution Methods 0.000 description 15
- 238000012360 testing method Methods 0.000 description 12
- 229960001866 silicon dioxide Drugs 0.000 description 10
- 238000011835 investigation Methods 0.000 description 9
- 229960001193 diclofenac sodium Drugs 0.000 description 8
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 8
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 7
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 6
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 229940041616 menthol Drugs 0.000 description 6
- -1 oleum Eucalypti Chemical compound 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 238000013112 stability test Methods 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 239000012738 dissolution medium Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000000691 measurement method Methods 0.000 description 3
- 235000011007 phosphoric acid Nutrition 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 229960004106 citric acid Drugs 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 230000003467 diminishing effect Effects 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960004838 phosphoric acid Drugs 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 238000013271 transdermal drug delivery Methods 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 229920002633 Kraton (polymer) Polymers 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 229940007061 capsicum extract Drugs 0.000 description 1
- 239000001943 capsicum frutescens fruit extract Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- 229960003608 clomifene Drugs 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- KPHWPUGNDIVLNH-UHFFFAOYSA-M diclofenac sodium Chemical compound [Na+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KPHWPUGNDIVLNH-UHFFFAOYSA-M 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 229960003898 flurbiprofen sodium Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002973 irritant agent Substances 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 229920001748 polybutylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The application provides a hot-melt type patch, which comprises a backing layer, an adhesive layer and a protective layer, wherein the adhesive layer comprises the following components in percentage by weight: 1-10% of a pharmaceutical active ingredient, 10-30% of a styrene-isoprene-styrene triblock copolymer, 8-20% of polyisobutylene, 8-25% of a tackifier and 20-70% of a plasticizer, wherein the pharmaceutical active ingredient is a non-steroidal anti-inflammatory agent, and the weight ratio of styrene/isoprene in the styrene-isoprene-styrene triblock copolymer is 15/85-25/75. The hot-melt patch provided by the application has the advantages that the adhesive property of the prepared patch is good, the patch is easy to peel off, the thermal stability is good, and the skin adhesion is free from residual glue and glue overflow phenomenon by optimizing the matrix styrene-isoprene-styrene triblock copolymer.
Description
Technical Field
The application belongs to the technical field of medicinal preparations, and particularly relates to a hot-melt type patch and a preparation method thereof.
Background
The transdermal drug delivery system is the third largest drug delivery system after oral administration and injection, and can deliver drugs into the systemic blood system of the human body through the epidermis and dermis tissues of the human body, thereby realizing local treatment on the affected part. External patches are the most common route of administration in transdermal drug delivery systems. The nonsteroidal anti-inflammatory drugs have the effects of relieving fever, easing pain, diminishing inflammation and the like, and are prepared into external analgesic drugs, and flurbiprofen patches, ketoprofen patches, loxoprofen sodium patches and the like are marketed at present.
The existing patch products often have the following problems: firstly, the release rate of the medicine of the patch is obviously changed under the high temperature condition, so that the curative effect can be influenced, the occurrence rate of adverse reaction can be increased, and even a safety event can occur; secondly, the adhesive surface of the patch flows easily (adhesive overflows at the edge) in the placing process, so that a black rubber ring is generated on the skin when the patch is used, and the using feeling is influenced; thirdly, the adhesive force of the patch is reduced in the placing process, so that the patch is not firmly adhered, and the using effect of a patient is affected.
Disclosure of Invention
It is an object of the present application to provide a non-steroidal anti-inflammatory drug hot-melt patch having excellent heat stability.
The second object of the present application is to provide a method for preparing the hot-melt type patch with excellent heat stability, which is simple and feasible and is easy to industrialize.
According to one aspect of the present application, there is provided a hot-melt type patch including a backing layer, an adhesive layer, and a protective layer, the adhesive layer including, in weight percent:
1-10% of a pharmaceutical active ingredient,
10-30% of a styrene-isoprene-styrene triblock copolymer,
8-20% of polyisobutylene,
8-25% of tackifier,
20-70% of plasticizer,
wherein the active pharmaceutical ingredient is a non-steroidal anti-inflammatory drug, and the weight ratio of styrene/isoprene in the styrene-isoprene-styrene triblock copolymer is 15/85-25/75.
Further, the hot-melt type patch, the adhesive layer comprises, in weight percent:
1-7% of a pharmaceutical active ingredient,
15-25% of a styrene-isoprene-styrene triblock copolymer,
10-15% of polyisobutene,
10-20% of tackifier,
30-60% of plasticizer.
Further, the melt index of the styrene-isoprene-styrene triblock copolymer is less than or equal to 20g/10min.
Further, the tackifier is hydrogenated rosin glyceride.
Further, the softening point of the hydrogenated rosin glyceride is 80-120 ℃.
Further, the non-steroidal anti-inflammatory drug is selected from at least one of loxoprofen or a pharmaceutically acceptable salt thereof, flurbiprofen or a pharmaceutically acceptable salt thereof, ketoprofen or a pharmaceutically acceptable salt thereof, diclofenac or a pharmaceutically acceptable salt thereof, indomethacin or a pharmaceutically acceptable salt thereof.
Further, the plasticizer is at least one selected from liquid paraffin, peanut oil and olive oil.
Further, the hot-melt patch also comprises at least one of a stabilizer, an antioxidant, a permeation enhancer, a pH regulator, an anti-irritant and a cosolvent.
Further, the stabilizer is silicon dioxide, and the use amount of the stabilizer is 0.2-3% by weight, and more preferably 0.5-2% by weight.
According to another aspect of the present application, there is also provided a method for preparing the above-mentioned hot-melt patch, comprising the steps of:
heating and melting the styrene-isoprene-styrene triblock copolymer, the polyisobutylene, the tackifier and part of plasticizer, optionally adding an antioxidant, stirring uniformly, adding a medicinal active ingredient and the rest plasticizer, optionally adding a cosolvent, a pH regulator, an anti-irritant, a permeation enhancer and a stabilizer, and stirring uniformly to obtain a paste;
and uniformly coating the paste on the protective layer, then attaching the paste to the backing layer, and finally cutting the paste into a proper size to obtain the hot-melt patch.
The application has the beneficial effects that:
the non-steroidal anti-inflammatory drug hot-melt patch is good in adhesive property, easy to peel and good in thermal stability, and has no residual adhesive and glue overflow phenomenon when being attached to skin by optimizing matrix styrene-isoprene-styrene triblock copolymer.
The preparation method of the nonsteroidal anti-inflammatory drug hot-melt type patch with excellent heat stability is simple and feasible and is easy to industrialize.
Detailed Description
The application provides a hot-melt type patch, which comprises a backing layer, an adhesive layer and a protective layer, wherein the adhesive layer comprises the following components in percentage by weight: 1-10% of a pharmaceutical active ingredient, 10-30% of a styrene-isoprene-styrene triblock copolymer, 8-20% of polyisobutylene, 8-25% of a tackifier and 20-70% of a plasticizer, wherein the pharmaceutical active ingredient is a non-steroidal anti-inflammatory agent, and the weight ratio of styrene/isoprene in the styrene-isoprene-styrene triblock copolymer is 15/85-25/75.
In the present application, styrene-isoprene-styrene triblock copolymer and polyisobutylene are substrates for patches, and styrene-isoprene-styrene triblock copolymer (SIS) refers to a block copolymer of styrene and isoprene, both ends of which contain polystyrene. Examples of such styrene-isoprene-styrene block copolymers include Kraton D1111, D1113, D1114, D1124, D1126, D1161, D1163, D1164, and paling petrochemical products 1105, 1106, 1209, 1124, 1126, 4019, 1125, 1128, 1108, 4016, and the like, and JSR SIS5002, SIS5229, SIS5250, SI5403, SIS5506, and the like. The application surprisingly finds that the thermal stability of the patch is better when the weight ratio of styrene/isoprene in the matrix is in the range of 15/85-25/75. It was further found that when the melt index of the styrene-isoprene-styrene triblock copolymer was 20g/10min or less, the thermal stability was further improved and the skin adhesion was free from the phenomenon of residual adhesive and flash adhesive.
The hot-melt type patch of the application comprises the following components in percentage by weight: 1-7% of a pharmaceutical active ingredient, 15-25% of a styrene-isoprene-styrene triblock copolymer, 10-15% of polyisobutylene, 10-20% of a tackifier and 30-60% of a plasticizer.
The tackifier of the present application is preferably rosin resin with rosin or rosin derivative as matrix, and the rosin resin has various kinds of available modes, such as KR-610, KR-614, KE604, KR-120, KE-100, KE-311, KE-359 and ESTERGUNM. The application discovers that the softening point of the tackifier can influence the stability of a product, when the tackifier with a low softening point (less than 80 ℃) is adopted, the thermal stability of the prepared patch is poor, glue overflow occurs, residues exist on skin after the patch is applied and used, and when the tackifier with a high softening point (more than 120 ℃) is adopted, the prepared patch is not beneficial to subsequent processing, so the hydrogenated rosin glyceride with the softening point of 80-120 ℃ is preferably adopted as an adhesive, and the thermal stability of the hot-melt patch is further improved.
In the present application, the pharmaceutically active ingredient is a non-steroidal anti-inflammatory drug, which has the effects of relieving fever, easing pain, diminishing inflammation, etc., and has been made into an analgesic for external use, and there are various products on the market, and the type of the non-steroidal anti-inflammatory drug in the present application is not limited, and it is preferable that at least one of loxoprofen or a pharmaceutically acceptable salt thereof, flurbiprofen or a pharmaceutically acceptable salt thereof, ketoprofen or a pharmaceutically acceptable salt thereof, diclofenac or a pharmaceutically acceptable salt thereof, indomethacin or a pharmaceutically acceptable salt thereof can be made into a hot-melt type patch.
The plasticizer of the present application may be selected from materials compatible with other matrix components, such as liquid paraffin, peanut oil, olive oil, etc. The liquid paraffin is particularly preferable, and 1 or 2 or more kinds of them may be used in combination.
Preferably, the hot melt patch of the present application may further include some additives conventionally used, such as stabilizers, antioxidants, permeation enhancers, pH adjusters, anti-irritants, co-solvents, and the like. The additives are added according to actual needs, and generally, the stabilizer is 0-3%, the antioxidant is 0-2%, the penetration enhancer is 0-3%, the pH regulator is 0-2%, the anti-irritant is 0-3%, and the cosolvent is 0-10%. Further, the antioxidant is preferably at least one of dibutyl hydroxy toluene, tocopherol acetate, propyl gallate and the like; the penetration enhancer is preferably at least one of clomiphene, azone, menthol, N-methylpyrrolidone, oleic acid, oleum Eucalypti, isopropyl myristate, etc.; the pH regulator is preferably at least one of lactic acid, tartaric acid, citric acid, phosphoric acid, etc.; the anti-irritant agent is preferably at least one of L-menthol, peppermint oil, capsaicin, capsicum extract, etc.; the cosolvent is selected from at least one of dimethyl sulfoxide (DMSO), propylene glycol and 1, 3-butanediol; the stabilizer is selected from silicon dioxide, zinc stearate, etc.
According to the application, when silicon dioxide is added into the hot-melt type patch as a stabilizer, the thermal stability of the patch is further improved, and the principle is that small silicon dioxide particles form a grid structure in a patch matrix, so that the colloid flow can be inhibited, the elastic modulus and the viscous modulus of the pressure-sensitive adhesive are improved, the cohesive force of the colloid can be enhanced, and the thermal stability of the patch is improved. The amount of the stabilizer silicon dioxide is 0.2-3%, preferably 0.5-2% by weight.
The backing layer of the patch of the present application is preferably a film or cloth of polyester, polyethylene polypropylene, polybutylene, nylon, polyurethane, etc.; the protective layer is preferably a pre-treated removable release paper or a film of polyethylene, polypropylene, polyester or the like.
According to another aspect of the present application, there is also provided a method for preparing the above-mentioned hot-melt patch, comprising the steps of:
heating and melting the styrene-isoprene-styrene triblock copolymer, the polyisobutylene, the tackifier and part of plasticizer, optionally adding an antioxidant, stirring uniformly, adding a medicinal active ingredient and the rest plasticizer, optionally adding a cosolvent, a pH regulator, an anti-irritant, a permeation enhancer and a stabilizer, and stirring uniformly to obtain a paste;
and uniformly coating the paste on the protective layer, then attaching the paste to the backing layer, and finally cutting the paste into a proper size to obtain the hot-melt patch.
The present application will be described in further detail below by taking as an example the pharmaceutically active ingredient selected from the group consisting of loxoprofen sodium, flurbiprofen and diclofenac sodium. The following examples are merely illustrative of the present application and should not be construed as limiting the application.
The reagents and raw materials used in the application are all commercially available.
Table 1. SIS technical characteristic parameters.
。
Table 2. Softening point of hydrogenated rosin glyceride.
。
Examples 1-8 are loxoprofen sodium patches, the formulations of which are shown in table 3 below.
Table 3 list of prescriptions for each example.
。
The preparation methods of examples 1 to 8 are as follows:
according to the component proportion, heating and melting SIS, polyisobutene, hydrogenated rosin glyceride and part of liquid paraffin, optionally adding dibutyl hydroxy toluene, stirring uniformly, then adding loxoprofen sodium and the rest liquid paraffin, optionally adding silicon dioxide, phosphoric acid and menthol, stirring uniformly to obtain paste;
and uniformly coating the paste on the protective layer, then attaching the paste to the backing layer, and finally cutting the paste into a proper size to obtain the loxoprofen sodium patch.
The formulation of the comparative example is shown in the following table.
Table 4 list of comparative examples prescriptions.
。
The preparation method of comparative examples 1 to 5 comprises the following steps:
according to the component proportion, heating and melting SIS, polyisobutene, hydrogenated rosin glyceride and part of liquid paraffin, adding dibutyl hydroxy toluene, stirring uniformly, adding loxoprofen sodium, the rest liquid paraffin, silicon dioxide, phosphoric acid and menthol, and stirring uniformly to obtain paste;
and uniformly coating the paste on the protective layer, then attaching the paste to the backing layer, and finally cutting the paste into a proper size to obtain the loxoprofen sodium patch.
Adhesion detection
The loxoprofen sodium patches prepared in examples 1 to 8 and comparative examples 1 to 5 of the present application were tested as follows.
Cutting the product into pieces of 5cm×10cm, and sticking on the inclined plane of adhesion tester with the adhesive surface facing upwards without gap between the adhesive surface and thick paper. The part above the inclined plane, which is more than 10cm away from the sample to be tested, is set as the center of the ball, and the maximum ball number which can prevent the adhesive surface from falling is recorded when the protective layer is torn off rapidly according to the legal operation (the first method of the fourth rule 0952 of the annual edition of Chinese pharmacopoeia 2015). The test was repeated 3 times, and the largest ball number that the adhesive surface could prevent from falling should be 19 or more.
Table 5 initial adhesion test results for each example and comparative example.
。
Thermal stability investigation test
The loxoprofen sodium patches prepared in examples 1 to 8 and comparative examples 1 to 5 of the present application were examined at 40℃and 60℃respectively, and the properties, initial adhesion and dissolution of the samples were examined, with the results shown in tables 6 to 8.
Table 6 results of examining the thermal stability of each example and comparative example.
。
Table 7 the results of the primary adhesion test were examined for thermal stability of each of examples and comparative examples.
。
The results in Table 6 and Table 7 show that the loxoprofen sodium patch prepared by the application has stable sample property and no obvious difference in appearance property under the condition of thermal stability investigation, and the initial adhesion detection results can meet the requirements.
Dissolution measurement
Dissolution rate measurement method: cutting the sample into round slices with the diameter of 3.0cm (wherein the release area is a circle with the diameter of 2.6 cm), peeling the protective layer, placing on a stainless steel plate, fixing the paste body with one side upwards, taking 700ml of sodium dodecyl sulfate solution (1-1000) as a dissolution medium, sampling and detecting at the temperature of 32 ℃ and the rotating speed of 100 revolutions per minute for 60 minutes, and calculating the dissolution rate.
Table 8 examples and commercial products thermal stability test dissolution test results.
。
The results show that the dissolution rate of the loxoprofen sodium patch prepared by the application is not obviously changed under the high-temperature investigation condition of 60 ℃, and the thermal stability of the loxoprofen sodium patch is better than that of a commercially available preparation.
Examples 9 to 16 are flurbiprofen patches, and the formulations are shown in the following table 9.
Table 9 list of prescriptions for each example.
。
The preparation methods of examples 9 to 16 are:
heating SIS, polyisobutylene, hydrogenated rosin glyceride and part of liquid paraffin to be melted according to the component proportion, optionally adding dibutyl hydroxy toluene, stirring uniformly, then adding flurbiprofen and the rest liquid paraffin, optionally adding silicon dioxide and menthol, and stirring uniformly to obtain paste;
and uniformly coating the paste on the protective layer, then attaching the paste to the backing layer, and finally cutting the paste into a proper size to obtain the flurbiprofen patch.
The formulation of the comparative example is shown in the following table.
Table 10 list the prescriptions for each comparative example.
。
The preparation method of the comparative examples 6-10 comprises the following steps:
heating SIS, polyisobutylene, dibutyl hydroxy toluene, hydrogenated rosin glyceride and part of liquid paraffin to be molten and uniformly stirring, then adding flurbiprofen, the rest of liquid paraffin, silicon dioxide and menthol, and uniformly stirring to obtain paste;
and uniformly coating the paste on the protective layer, then attaching the paste to the backing layer, and finally cutting the paste into a proper size to obtain the flurbiprofen patch.
Adhesion detection
The flurbiprofen patches prepared in examples 9 to 16 and comparative examples 6 to 10 of the present application were tested as follows.
Cutting the product into pieces of 5cm×10cm, and sticking on the inclined plane of adhesion tester with the adhesive surface facing upwards without gap between the adhesive surface and thick paper. The part above the inclined plane, which is more than 10cm away from the sample to be tested, is set as the center of the ball, and the maximum ball number which can prevent the adhesive surface from falling is recorded when the protective layer is torn off rapidly according to the legal operation (the first method of the fourth rule 0952 of the annual edition of Chinese pharmacopoeia 2015). The test was repeated 3 times, and the largest ball number that the adhesive surface could prevent from falling should be 19 or more.
Table 11 initial adhesion test results for each example and comparative example.
。
Thermal stability investigation test
The flurbiprofen patches prepared in examples 9 to 16 and comparative examples 6 to 10 of the present application were examined at 40℃and 60℃respectively, and the properties, initial adhesion and dissolution of the samples were examined, with the results shown in tables 12 to 13.
Table 12 results of examining the thermal stability of each example and comparative example.
。
Table 13 the results of the primary adhesion test were examined for thermal stability of each of the examples and comparative examples.
。
The results in Table 12 and Table 13 show that the flurbiprofen patch prepared by the application has stable sample properties under the condition of thermal stability investigation, has no obvious difference in appearance properties, and meets the requirements in initial adhesion detection results.
Dissolution measurement
Dissolution rate measurement method: cutting the sample into round slices with the diameter of 3.0cm (wherein the release area is a circle with the diameter of 2.6 cm), peeling the protective layer, placing on a stainless steel plate, fixing the paste body with one side upwards, taking 700ml of sodium dodecyl sulfate solution (1-1000) as a dissolution medium, sampling and detecting at the temperature of 32 ℃ and the rotating speed of 50 revolutions per minute for 60 minutes, and calculating the dissolution rate.
Table 14 examples and commercial products thermal stability test results.
。
The result shows that the flurbiprofen patch prepared by the application has no obvious change of dissolution rate under the high temperature investigation condition of 60 ℃, and has better thermal stability than the commercially available preparation.
Examples 17 to 24 are diclofenac sodium patches, and the prescription is shown in table 15 below.
Table 15 list of prescriptions for each example.
。
The formulation of the comparative example is shown in the following table.
Table 16 a list of comparative examples prescriptions.
。
The preparation methods of examples 17-24 and comparative examples 11-15 were:
according to the component proportion, heating and melting SIS, polyisobutylene, dibutyl hydroxy toluene, hydrogenated rosin glyceride and liquid paraffin, uniformly stirring, then adding sodium diclofenac, dimethyl sulfoxide, menthol, silicon dioxide and citric acid, and uniformly stirring to obtain paste (the components which are not added in the prescription);
and uniformly coating the paste on the protective layer, then attaching the paste to the backing layer, and finally cutting the paste into a proper size to obtain the diclofenac sodium patch.
Adhesion detection
The diclofenac sodium patches prepared in examples 17 to 24 and comparative examples 11 to 15 of the present application were tested as follows.
Cutting the product into pieces of 5cm×10cm, and sticking on the inclined plane of adhesion tester with the adhesive surface facing upwards without gap between the adhesive surface and thick paper. The part above the inclined plane, which is more than 10cm away from the sample to be tested, is set as the center of the ball, and the maximum ball number which can prevent the adhesive surface from falling is recorded when the protective layer is torn off rapidly according to the legal operation (the first method of the fourth rule 0952 of the annual edition of Chinese pharmacopoeia 2015). The test was repeated 3 times, and the largest ball number that the adhesive surface could prevent from falling should be 15 or more.
Table 17 initial adhesion test results for each example and comparative example.
。
Thermal stability investigation test
The diclofenac sodium patches prepared in examples 17 to 24 and comparative examples 11 to 15 of the present application were examined at 40℃and 60℃respectively, and the properties, initial adhesion and dissolution of the samples were examined, with the results shown in tables 18 to 19.
Table 18 thermal stability test results for each example and comparative example.
。
Table 19 the results of the primary adhesion test were examined for thermal stability of each of examples and comparative examples.
。
The results in Table 18 and Table 19 show that the diclofenac sodium patch prepared by the application has stable sample properties under the condition of thermal stability investigation, has no obvious difference in appearance properties, and meets the requirements in initial adhesion detection results.
Dissolution measurement
Dissolution rate measurement method: cutting the sample into round slices with the diameter of 3.0cm (wherein the release area is a circle with the diameter of 2.6 cm), peeling the protective layer, placing on a stainless steel plate, fixing the paste body with one side upwards, taking 700ml of sodium dodecyl sulfate solution (1-1000) as a dissolution medium, sampling and detecting at the temperature of 32 ℃ and the rotating speed of 100 revolutions per minute for 60 minutes, and calculating the dissolution rate.
Table 20 examples and commercial products thermal stability test dissolution test results.
。
The result shows that the dissolution rate of the diclofenac sodium patch prepared by the application is not obviously changed under the high temperature investigation condition of 60 ℃, and the heat stability of the diclofenac sodium patch is better than that of a commercially available preparation.
The foregoing is a further detailed description of the application in connection with specific embodiments, and it is not intended that the application be limited to such description. It will be apparent to those skilled in the art that several simple deductions or substitutions may be made without departing from the spirit of the application, and these should be considered to be within the scope of the application.
Claims (10)
1. A hot melt patch comprising a backing layer, an adhesive layer and a protective layer, wherein the adhesive layer comprises, in weight percent:
1-10% of a pharmaceutical active ingredient,
10-30% of a styrene-isoprene-styrene triblock copolymer,
8-20% of polyisobutylene,
8-25% of tackifier,
20-70% of plasticizer,
wherein the active pharmaceutical ingredient is a non-steroidal anti-inflammatory drug, and the weight ratio of styrene/isoprene in the styrene-isoprene-styrene triblock copolymer is 15/85-25/75.
2. The hot melt adhesive patch according to claim 1, wherein said adhesive layer comprises, in weight percent:
1-7% of a pharmaceutical active ingredient,
15-25% of a styrene-isoprene-styrene triblock copolymer,
10-15% of polyisobutene,
10-20% of tackifier,
30-60% of plasticizer.
3. A hot-melt type patch according to claim 1 or 2, wherein,
the melt index of the styrene-isoprene-styrene triblock copolymer is less than or equal to 20g/10min.
4. The hot-melt patch according to any one of claim 1 to 3,
the tackifier is hydrogenated rosin glyceride.
5. The hot-melt type patch according to claim 4, wherein,
the softening point of the hydrogenated rosin glyceride is 80-120 ℃.
6. The hot-melt patch according to any one of claims 1 to 5, wherein,
the non-steroidal anti-inflammatory drug is selected from at least one of loxoprofen or a medicinal salt thereof, flurbiprofen or a medicinal salt thereof, ketoprofen or a medicinal salt thereof, diclofenac or a medicinal salt thereof, indomethacin or a medicinal salt thereof.
7. The hot-melt patch according to any one of claims 1 to 6, wherein,
the plasticizer is at least one selected from liquid paraffin, peanut oil and olive oil.
8. The hot-melt patch according to any one of claims 1 to 7, wherein,
and at least one of stabilizer, antioxidant, penetration enhancer, pH regulator, anti-irritant and cosolvent.
9. The hot-melt type patch according to claim 8, wherein,
the stabilizer is silicon dioxide, and the dosage of the stabilizer is 0.2-3%, preferably 0.5-2% by weight.
10. The method for preparing a hot-melt type patch according to any one of claims 1 to 9, comprising the steps of:
heating and melting the styrene-isoprene-styrene triblock copolymer, the polyisobutylene, the tackifier and part of plasticizer, optionally adding an antioxidant, stirring uniformly, adding a medicinal active ingredient and the rest plasticizer, optionally adding a cosolvent, a pH regulator, an anti-irritant, a permeation enhancer and a stabilizer, and stirring uniformly to obtain a paste;
and uniformly coating the paste on the protective layer, then attaching the paste to the backing layer, and finally cutting the paste into a proper size to obtain the hot-melt patch.
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| CN202311201211.7A CN117159508A (en) | 2023-09-18 | 2023-09-18 | Hot-melt patch and preparation method thereof |
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| CN202311201211.7A CN117159508A (en) | 2023-09-18 | 2023-09-18 | Hot-melt patch and preparation method thereof |
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1409628A (en) * | 1999-12-15 | 2003-04-09 | 久光制药株式会社 | Adhesive preparations |
| CN1424908A (en) * | 2000-04-18 | 2003-06-18 | 久光制药株式会社 | Patch containing anti-inflammatory agent |
| JP2004043512A (en) * | 2003-11-10 | 2004-02-12 | Hisamitsu Pharmaceut Co Inc | Antiphlogistic and analgesic plaster |
| CN101052384A (en) * | 2004-11-05 | 2007-10-10 | 立德化学株式会社 | Non-aqueous transdermal absorption prepn. contg. non-steroid antiphlogistic analgesic |
| JP2011020997A (en) * | 2009-03-19 | 2011-02-03 | Kyoritsu Yakuhin Kogyo Kk | Patch for external use |
| JP2015013847A (en) * | 2012-06-22 | 2015-01-22 | 興和株式会社 | Pharmaceutical composition 2 containing loxoprofen |
| CN106692111A (en) * | 2015-11-13 | 2017-05-24 | 北京泰德制药股份有限公司 | External skin patch containing ketoprofen and preparation method of external skin patch |
| CN106692110A (en) * | 2015-08-19 | 2017-05-24 | 天津市山佳医药科技有限公司 | Aryl propionic acid type nonsteroidal anti-inflammatory drug patch and preparation method thereof |
| CN116747208A (en) * | 2023-08-10 | 2023-09-15 | 湖南九典制药股份有限公司 | Ketoprofen patch and preparation method thereof |
-
2023
- 2023-09-18 CN CN202311201211.7A patent/CN117159508A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1409628A (en) * | 1999-12-15 | 2003-04-09 | 久光制药株式会社 | Adhesive preparations |
| CN1424908A (en) * | 2000-04-18 | 2003-06-18 | 久光制药株式会社 | Patch containing anti-inflammatory agent |
| JP2004043512A (en) * | 2003-11-10 | 2004-02-12 | Hisamitsu Pharmaceut Co Inc | Antiphlogistic and analgesic plaster |
| CN101052384A (en) * | 2004-11-05 | 2007-10-10 | 立德化学株式会社 | Non-aqueous transdermal absorption prepn. contg. non-steroid antiphlogistic analgesic |
| JP2011020997A (en) * | 2009-03-19 | 2011-02-03 | Kyoritsu Yakuhin Kogyo Kk | Patch for external use |
| JP2015013847A (en) * | 2012-06-22 | 2015-01-22 | 興和株式会社 | Pharmaceutical composition 2 containing loxoprofen |
| CN106692110A (en) * | 2015-08-19 | 2017-05-24 | 天津市山佳医药科技有限公司 | Aryl propionic acid type nonsteroidal anti-inflammatory drug patch and preparation method thereof |
| CN106692111A (en) * | 2015-11-13 | 2017-05-24 | 北京泰德制药股份有限公司 | External skin patch containing ketoprofen and preparation method of external skin patch |
| CN116747208A (en) * | 2023-08-10 | 2023-09-15 | 湖南九典制药股份有限公司 | Ketoprofen patch and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 盖德化工网: "SIS/美国kraton/D-1107高断裂伸长率", pages 1 - 2, Retrieved from the Internet <URL:https://china.guidechem.com/trade/pdetail4371601.html> * |
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