CN109481423B - Diclofenac salt transdermal patch and preparation method thereof - Google Patents

Diclofenac salt transdermal patch and preparation method thereof Download PDF

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CN109481423B
CN109481423B CN201811389124.8A CN201811389124A CN109481423B CN 109481423 B CN109481423 B CN 109481423B CN 201811389124 A CN201811389124 A CN 201811389124A CN 109481423 B CN109481423 B CN 109481423B
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diclofenac salt
diclofenac
transdermal patch
sensitive adhesive
patch
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CN109481423A (en
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张锁慧
汪宝瑞
高云华
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Technical Institute of Physics and Chemistry of CAS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The invention discloses a diclofenac salt transdermal patch and a preparation method thereof. The invention firstly discloses a diclofenac salt transdermal patch, which sequentially comprises a backing film, a drug storage and a protective film from top to bottom; wherein, the raw materials of the drug reservoir comprise diclofenac salt, a pressure-sensitive adhesive matrix and a solubilizer. The invention further discloses a preparation method of the diclofenac salt transdermal patch. The diclofenac salt transdermal patch of the invention screens the solubilizer and the addition amount thereof through an orthogonal test to increase the solubility of the diclofenac salt in the pressure-sensitive adhesive matrix, promote the drug to permeate the skin, effectively improve the transdermal permeation amount of the patch per unit area and the stability of the patch, and improve the bioavailability of the diclofenac salt.

Description

Diclofenac salt transdermal patch and preparation method thereof
Technical Field
The invention relates to the technical field of medicines. More particularly, relates to a diclofenac salt transdermal patch and a preparation method thereof.
Background
Diclofenac and its salt are important anthranilic acid non-steroidal antipyretic analgesic and anti-inflammatory drugs, and their pharmacological actions are mainly to inhibit the synthesis of prostaglandin in the body. Prostaglandins have high biological activity and participate in various pathological processes such as fever, pain, inflammation and the like of organisms. Diclofenac combines with cyclooxygenase to cover the active center of enzyme, thereby blocking the metabolic process of converting arachidonic acid into prostaglandin catalyzed by the enzyme, relieving pain, having anti-inflammatory effect, having small central side effect and low toxicity, being a better analgesic, well relieving arthralgia and improving the activity of the medicament. The traditional Chinese medicine composition is mainly used for treating rheumatoid arthritis, osteoarthritis and ankylosing spondylitis clinically; various soft tissue swelling and pain, including lumbago, backache, scapulohumeral periarthritis, synovitis, tenosynovitis, and cervical spondylopathy; soft tissue injuries, including contusions, pounding injuries, sprains, lacerations, strains, and the like. It also has good therapeutic effect on toothache, dysmenorrhea, cancer, and postoperative pain.
The diclofenac and the salt thereof are commonly used preparations including tablets, capsules, gels, creams, patches and the like, wherein the transdermal patch has the advantages of no liver first pass effect, no influence of gastric emptying rate and the like, high bioavailability, convenient use, no pain, capability of withdrawing or interrupting treatment at any time, accurate administration dosage, fixed absorption area, stable blood concentration and the like. However, diclofenac salts have a low oil-water distribution coefficient (LogP) and low solubility in water or fat-soluble ingredients, and thus have a problem that the drug in the patch is likely to crystallize out.
Therefore, there is a need to provide a new diclofenac salt transdermal patch that solves at least one of the above problems.
Disclosure of Invention
The invention aims to provide a diclofenac salt transdermal patch with high drug loading, stable drug and good transdermal permeability.
Another object of the present invention is to provide a method for preparing the above diclofenac salt transdermal patch.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a diclofenac salt transdermal patch, which sequentially comprises a backing film, a drug storage and a protective film from top to bottom; wherein, the raw materials of the drug reservoir comprise diclofenac salt, a pressure-sensitive adhesive matrix and a solubilizer.
Further, the solubilizer includes but is not limited to one or a mixture of lactic acid, sodium lactate, boric acid and tartaric acid.
Further, the diclofenac salt includes, but is not limited to, a mixture of one or more of diclofenac sodium, diclofenac diethylamine, diclofenac N- (2-hydroxyethyl) pyrrolidine.
Further, the pressure-sensitive adhesive matrix is an acrylate pressure-sensitive adhesive and comprises an acrylate polymer and a solvent, wherein the content of the acrylate polymer accounts for 20% -50% of the total mass of the acrylate pressure-sensitive adhesive; preferably, the solvent includes but is not limited to one or a mixture of several of ethyl acetate, heptane, hexane, methanol, ethanol, isopropanol, 2, 4-pentanedione, toluene and xylene.
Further, the molar ratio of the diclofenac salt to the solubilizer is 1:0.05-1:5, preferably 1:0.2-1: 2.
Further, the content of the diclofenac salt is 0.5-20%, preferably 1-10% of the total mass of the drug reservoir.
Further, the backing film is one or more layers of composite films, and the material of the backing film comprises one or more of polyethylene terephthalate, polypropylene, polyethylene, ethylene-vinyl acetate copolymer and polyurethane.
Further, the thickness of the backing film is 30-300 μm.
Further, the material of the protective film is one or a mixture of a plurality of polyethylene terephthalate, polyethylene and polypropylene films, the surfaces of which are subjected to plasma treatment and fluorine or silicon coating treatment, and the polyethylene terephthalate is preferably subjected to fluorine coating treatment.
Further, the thickness of the protective film is 20 to 300 μm.
Further, the area of the diclofenac salt transdermal patch is 5-100cm2。
Preferably, the diclofenac salt content per square centimeter of the diclofenac salt transdermal patch ranges from 0.2 to 2 mg.
The invention further provides a preparation method of the diclofenac salt transdermal patch, which comprises the following steps:
adding diclofenac salt into ethanol, mixing, and adding solubilizer;
adding pressure sensitive adhesive matrix, stirring, standing to remove bubbles, coating on protective film, drying, covering with backing film, and pressing.
Further, the coating thickness is 50-1000 μm; preferably 300-600 μm.
Further, the stirring is constant temperature magnetic stirring at 60 ℃ for 30-60 min.
Further, the drying is carried out for 10-20min at 70-90 ℃.
The invention has the following beneficial effects:
the diclofenac salt transdermal patch of the invention screens the solubilizer and the addition amount thereof through an orthogonal test to increase the solubility of the diclofenac salt in the pressure-sensitive adhesive matrix, promote the drug to permeate the skin, effectively improve the transdermal permeation amount of the patch per unit area and the stability of the patch, and improve the bioavailability of the diclofenac salt.
Drawings
The following describes embodiments of the present invention in further detail with reference to the accompanying drawings.
FIG. 1 shows a polarization microscope photograph of diclofenac sodium transdermal patches with test numbers 1 to 9 in the test examples.
Fig. 2 shows a polarization microscope photograph of a commercially available diclofenac sodium patch in the test example.
Fig. 3 shows the absolute value of the cumulative release amount of diclofenac sodium patch 12h in the test example: a: patch No. 2; b: patch No. 3; c: patch No. 9; d: diclofenac sodium patches are commercially available.
Fig. 4 shows the relative values of the cumulative release amount of diclofenac sodium patch 12h in the test examples: a: patch No. 2; b: patch No. 3; c: patch No. 9; d: diclofenac sodium patches are commercially available.
Detailed Description
In order to more clearly illustrate the invention, the invention is further described below with reference to preferred embodiments and the accompanying drawings. Similar parts in the figures are denoted by the same reference numerals. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.
In a first aspect, the invention provides a diclofenac salt transdermal patch, which sequentially comprises a backing membrane, a drug reservoir and a protective membrane from top to bottom; wherein, the raw materials of the drug reservoir comprise diclofenac salt, a pressure-sensitive adhesive matrix and a solubilizer.
Further, the solubilizer includes but is not limited to one or a mixture of lactic acid, sodium lactate, boric acid and tartaric acid, and the solubilizer can effectively increase the solubility of the diclofenac salt in the pressure-sensitive adhesive.
Further, the diclofenac salt includes, but is not limited to, a mixture of one or more of diclofenac sodium, diclofenac diethylamine, diclofenac N- (2-hydroxyethyl) pyrrolidine.
Further, the pressure-sensitive adhesive matrix is an acrylate pressure-sensitive adhesive and comprises an acrylate polymer and a solvent, wherein the content of the acrylate polymer accounts for 20% -50% of the total mass of the acrylate pressure-sensitive adhesive; preferably, the solvent is one or a mixture of more of ethyl acetate, heptane, hexane, methanol, ethanol, isopropanol, 2, 4-pentanedione, toluene and xylene.
The acrylate pressure-sensitive adhesive has the characteristics of small stimulation to skin, less anaphylactic reaction, stable property, no residue after use and the like.
Further, the molar ratio of the diclofenac salt to the solubilizer is 1:0.05 to 1:5, preferably 1:0.2 to 1:2, and may be, for example, 1:0.05, 1:0.2, 1: 1, 1: 1.5, 1:2, 1: 3, 1: 4, 1:5, etc. When the molar ratio of diclofenac salt to solubilizer is outside the above range, crystals of diclofenac salt are precipitated from the patch, and the transdermal permeability of the patch is deteriorated.
Further, the content of the diclofenac salt is 0.5% to 20%, preferably 1% to 10%, of the total mass of the drug depot, and for example, may be 0.5%, 1%, 3%, 5%, 7%, 9%, 10%, 11%, 13%, 15%, 17%, 20%, and the like. When the content of diclofenac salt is low, the transdermal permeability of the patch is poor, and the treatment effect is weakened; if the content of the diclofenac salt is too high, crystals can be precipitated in the patch, and the bioavailability of the diclofenac salt is reduced.
Further, the backing film is one or more layers of composite films, and the material of the backing film comprises one or more of polyethylene terephthalate, polypropylene, polyethylene, ethylene-vinyl acetate copolymer and polyurethane.
Further, the thickness of the backing film is 30-300 μm; for example, it may be 30 μm, 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, or the like.
Further, the material of the protective film is one or a mixture of a plurality of polyethylene terephthalate, polyethylene and polypropylene films, the surfaces of which are subjected to plasma treatment and fluorine or silicon coating treatment, and the polyethylene terephthalate is preferably subjected to fluorine coating treatment.
Further, the thickness of the protective film is 20-300 μm; for example, it may be 20 μm, 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, or the like.
Further, the area of the diclofenac salt transdermal patch is 5-100cm2(ii) a For example, it may be 5cm2、20cm2、40cm2、60cm2、80cm2、100cm2And so on.
Preferably, the content range of the drug in the diclofenac salt transdermal patch per square centimeter is 0.2-2 mg; for example, it may be 0.2mg, 0.5mg, 1mg, 1.5mg, 2mg, etc.
In a second aspect, the invention provides a method for preparing the diclofenac salt transdermal patch, which comprises the following steps:
adding diclofenac salt into ethanol, mixing, and adding solubilizer;
adding pressure sensitive adhesive matrix, stirring, standing to remove bubbles, coating on protective film, drying, covering with backing film, and pressing.
Further, the coating thickness is 50-1000 μm; preferably 300-600 μm; for example, it may be 50 μm, 100 μm, 300 μm, 500 μm, 600 μm, 700 μm, 900 μm, 1000 μm, or the like.
Further, the stirring is constant temperature magnetic stirring at 60 ℃ for 30-60 min.
Further, the drying is carried out for 10-20min at 70-90 ℃.
The present invention will be further described below by way of specific examples.
In the present invention, the raw materials and equipment used are commercially available or commonly used in the art, unless otherwise specified. The methods in the following examples are conventional in the art unless otherwise specified.
EXAMPLE 1A diclofenac sodium transdermal patch
1. Weighing the following raw materials:
Figure BDA0001872249040000051
2. preparation of transdermal patch
Adding diclofenac sodium into ethanol, mixing, adding lactic acid to dissolve diclofenac sodium, adding DURO-TAK 87-2677 medical pressure-sensitive adhesive (containing acrylate and vinyl acetate copolymer 39.5%, ethyl acetate 22.4%, isopropanol 22.4%, heptane 12.7%, and toluene 3%), magnetically stirring at 60 deg.C for 1 hr, standing for 1 hr to remove air bubbles, coating onto protective film with a coating thickness of 300 μm, oven drying at 70 deg.C for 20min, covering with backing film, pressing, cutting, and sealing with aluminum plastic bag. The protective film is made of polyethylene glycol terephthalate which is coated with fluorine, and the thickness of the protective film is 200 mu m; the backing film is made of polyethylene terephthalate and has a thickness of 100 mu m.
In application, the protective film is torn off, and the side containing the drug reservoir is adhered to skin.
The result of in vitro transdermal experiment shows that the 24-hour accumulated release amount of the patch can reach 31.77 mu g/cm2。
Example 2A diclofenac sodium transdermal patch
1. Weighing the following raw materials:
Figure BDA0001872249040000052
2. preparation of transdermal patch
Adding diclofenac sodium into ethanol, uniformly mixing, adding boric acid to promote the dissolution of the diclofenac sodium, adding DURO-TAK 387-2510 medical pressure-sensitive adhesive (containing 40.5% of acrylate polymer, 54.1% of ethyl acetate and 5.4% of hexane), magnetically stirring at a constant temperature of 60 ℃ for 30min, standing for 1 h to remove bubbles, coating on a protective film with the coating thickness of 600 mu m, drying at 90 ℃ for 10min, covering a backing film, compacting, cutting, and sealing and storing an aluminum plastic bag. The protective film is made of silicon-coated polyethylene glycol terephthalate and has the thickness of 30 mu m; the backing film is made of polyurethane and has a thickness of 300 μm.
In application, the protective film is torn off, and the side containing the drug reservoir is adhered to skin.
The result of in vitro transdermal experiment shows that the 24-hour accumulated release amount of the patch can reach 16.95 mu g/cm2。
EXAMPLE 3A diclofenac sodium transdermal patch
1. Weighing the following raw materials:
Figure BDA0001872249040000061
2. preparation of transdermal patch
Adding diclofenac sodium into ethanol, uniformly mixing, adding tartaric acid to promote the dissolution of diclofenac sodium, adding DURO-TAK 387-2510 medical pressure-sensitive adhesive, magnetically stirring at a constant temperature of 60 ℃ for 45min to completely dissolve diclofenac sodium, standing for 1 h to remove bubbles, coating on a protective film, coating the protective film with the thickness of 1000 mu m, drying at 80 ℃ for 15min, covering a backing film, compacting, cutting, and sealing and storing an aluminum plastic bag. The protective film is made of polypropylene and has the thickness of 300 mu m; the backing film is made of ethylene-vinyl acetate copolymer and has a thickness of 20 μm.
In application, the protective film is torn off, and the side containing the drug reservoir is adhered to skin.
The result of in vitro transdermal experiment shows that the 24-hour accumulated release amount of the patch can reach 50.43 mug/cm2。
Screening of drug depot formulations in test examples
In the experimental example, 2 4-factor 3 horizontal orthogonal tests are carried out to screen the influence of diclofenac salt, medical pressure-sensitive adhesive, solubilizer, molar ratio of diclofenac sodium to solubilizer and drug content of 5 factors on crystallinity, adhesiveness and transdermal permeability of the diclofenac salt transdermal patch.
The specific test method comprises the following steps:
adding diclofenac sodium into a proper amount of ethanol, uniformly mixing, adding a solubilizer, adding the medical pressure-sensitive adhesive, magnetically stirring at a constant temperature of 60 ℃ for 1 hour to completely dissolve the diclofenac sodium, standing for 1 hour to remove bubbles to obtain a drug-containing pressure-sensitive adhesive solution, and checking the crystallinity;
further, the medicated pressure sensitive adhesive solution is coated on a protective film with a coating thickness of 300 μm, dried at 70 deg.C for 20min, covered with a backing film, compressed, and cut to obtain transdermal patch.
The results of the crystallinity examination by polarization microscopy showed that, as shown in FIGS. 1 and 2, formulations 3 and 9 showed no crystal precipitation, and formulation 2 showed a small amount of crystal precipitation. Formulations 1, 4, 5, 6, 7, 8 and commercially available patches have crystal precipitates. Since crystallization in the patch deteriorates the transdermal permeability of the patch, the formulations 2, 3 and 9 were selected for the adhesion test and transdermal test of the patch.
The adhesion was expressed by initial adhesion, holding adhesion and peel strength, and the results are shown in table 1: the initial adhesion and the holding adhesion of the prescription patch 2 and 3 are close to those of the commercially available patch, but the peeling test causes stringiness, which does not meet the regulation related to the Chinese pharmacopoeia of 2015 edition. The patch with the prescription of No. 9 has proper initial adhesion, holding adhesion and peeling strength, so the prescription of No. 9 is selected as the optimal prescription.
In vitro transdermal experiments, the skin of the pig ear was fixed to a modified Franz diffusion cell with the dermis facing the receiving chamber and the stratum corneum facing the feeding chamber. The patch is applied to the stratum corneum and a suitable amount of phosphate buffer with pH 7.4 is added into the receiving chamber. Samples were taken at 37 ℃ in a thermostatic water bath cycle with magnetic stirring for 1, 2, 3, 4, 5, 6, 8, 10, 12 hours and the sample concentration was determined by high performance liquid chromatography, and the results are shown in FIGS. 3 and 4, from which it can be seen that: the relative values of the cumulative release amount per unit area of the patches prepared by the medicine-containing pressure-sensitive adhesive of prescriptions 2, 3 and 9 have no obvious difference. The absolute value of the cumulative release amount per unit area is mainly related to the drug content of the patch. The higher the drug content per unit area of the patch, the higher the transdermal permeation amount. The lactic acid is used as a solubilizer, so that the dosage of the diclofenac sodium in the drug-containing pressure-sensitive adhesive can be obviously increased, the diclofenac sodium is dispersed in the pressure-sensitive adhesive in a molecular form, and the transdermal permeation quantity of the drug per unit area and the stability of the patch are improved. The medicine-containing pressure-sensitive adhesive of prescription No. 9 has high stability through crystallinity examination, and the adhesive force of the patch is moderate, and the transdermal permeability is good.
TABLE 1 results of drug depot formulation screening
Figure BDA0001872249040000071
Figure BDA0001872249040000081
Note: in the tables a, b and c, the products DURO-TAK 387-2510, DURO-TAK87-6908 (containing 38% polyisobutylene and 62% n-heptane) and DURO-TAK 87-2677, respectively, are pressure-sensitive adhesives for medical use, which are available from Henkel.
Table 2 cumulative release results for drug depot formulations of different compositions and contents
Figure BDA0001872249040000082
Note: in the table, the molar ratio of the raw material drug to the solubilizer is fixed to be 1: 1; a, b and c are respectively DURO-TAK 387-2510, DURO-TAK87-6908 (containing 38% of polyisobutene and 62% of n-heptane) and DURO-TAK 87-2677 products which are medical pressure-sensitive adhesives purchased from Henkel company.
The factors of the diclofenac salt species, the solubilizer species, the molar ratio of the diclofenac salt to the solubilizer, the drug content and the like are considered, and as shown in tables 1 and 2, the solubilizing agent provided by the invention can be used for increasing the solubility of the diclofenac salt in the medical pressure-sensitive adhesive, the transdermal permeability of a drug reservoir and the transdermal cumulative release amount.
It should be understood that the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention, and it will be obvious to those skilled in the art that other variations or modifications may be made on the basis of the above description, and all embodiments may not be exhaustive, and all obvious variations or modifications may be included within the scope of the present invention.

Claims (15)

1. A diclofenac salt transdermal patch is characterized by comprising a backing film, a drug storage and a protective film from top to bottom in sequence; wherein, the raw materials of the drug reservoir comprise diclofenac salt, a pressure-sensitive adhesive matrix and a solubilizer; the solubilizer is boric acid, and the molar ratio of the diclofenac salt to the solubilizer is 1:0.05-1: 5; the content of the diclofenac salt is 0.5 to 20 percent of the total mass of the drug reservoir.
2. The diclofenac salt transdermal patch of claim 1, wherein the molar ratio of diclofenac salt to solubilizer is 1:0.2 to 1: 2.
3. The transdermal patch of claim 1, wherein the diclofenac salt is present in an amount of 1-10% by weight of the total mass of the drug depot.
4. The diclofenac salt transdermal patch of claim 1, wherein the diclofenac salt is a mixture of one or more of diclofenac sodium, diclofenac diethylamine, diclofenac N- (2-hydroxyethyl) pyrrolidine.
5. The diclofenac salt transdermal patch of claim 1, wherein the pressure sensitive adhesive matrix is an acrylate pressure sensitive adhesive comprising an acrylate polymer and a solvent.
6. The diclofenac salt transdermal patch according to claim 5, wherein the content of the acrylate copolymer is 20-50% of the total mass of the acrylate pressure sensitive adhesive matrix.
7. The diclofenac salt transdermal patch of claim 5, wherein the solvent is one or a mixture of ethyl acetate, heptane, hexane, methanol, ethanol, isopropanol, 2, 4-pentanedione, toluene, xylene.
8. The diclofenac salt transdermal patch of claim 1, wherein the backing film is one or more layers of composite film, and the material of the backing film comprises one or more of polyethylene terephthalate, polypropylene, polyethylene, ethylene-vinyl acetate copolymer, and polyurethane.
9. The diclofenac salt transdermal patch of claim 1, wherein the backing film has a thickness of 30-300 μm.
10. The diclofenac salt transdermal patch according to claim 1, wherein the protective film is made of one or more of polyethylene terephthalate, polyethylene and polypropylene films, the surface of which is treated by plasma, fluorine or silicon.
11. The diclofenac salt transdermal patch according to claim 1, wherein the protective film is made of polyethylene terephthalate with fluorine-coated surface.
12. The diclofenac salt transdermal patch of claim 1, wherein the protective film has a thickness of 20-300 μm.
13. A process for the preparation of a transdermal patch of diclofenac salt according to any of claims 1 to 12, comprising the following steps:
adding diclofenac salt into ethanol, mixing, and adding solubilizer;
adding pressure sensitive adhesive matrix, stirring, standing to remove bubbles, coating on protective film, drying, covering with backing film, and pressing.
14. The method of claim 13, wherein the coating thickness is 50 to 1000 μm.
15. The method as claimed in claim 13, wherein the coating thickness is 300-600 μm.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4738848A (en) * 1985-06-04 1988-04-19 Nitto Electric Industrial Co., Ltd. Anti-inflammatory analgesic adhesive preparation
CN1462187A (en) * 2001-05-23 2003-12-17 株式会社脱苦海 Analgesic/antiinflammatary patches for topical use
WO2005102306A1 (en) * 2004-04-23 2005-11-03 Hisamitsu Pharmaceutical Co., Inc. Anti-inflammatory analgesic adhesive patch

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4738848A (en) * 1985-06-04 1988-04-19 Nitto Electric Industrial Co., Ltd. Anti-inflammatory analgesic adhesive preparation
CN1462187A (en) * 2001-05-23 2003-12-17 株式会社脱苦海 Analgesic/antiinflammatary patches for topical use
WO2005102306A1 (en) * 2004-04-23 2005-11-03 Hisamitsu Pharmaceutical Co., Inc. Anti-inflammatory analgesic adhesive patch

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