Transdermal patch based on carbamazepine and preparation method

Abstract

The invention is applicable to the technical field of drug-loaded polymer medical preparations, and provides a carbamazepine-based transdermal patch and a preparation method thereof, and the carbamazepine-based transdermal patch comprises a drug-containing layer, a backing layer and a protective layer; the active ingredient of the medicine-containing layer is carbamazepine or pharmaceutically acceptable salt thereof, and the content of carbamazepine or pharmaceutically acceptable salt accounts for 5-35% of the total mass of the medicine-containing layer; the matrix of the drug-containing layer is composed of one or more of polyvinyl alcohol, acrylic acid pressure-sensitive adhesive, polybutylene pressure-sensitive adhesive and polysiloxane pressure-sensitive adhesive, and the content of the matrix accounts for 50%-80% of the total mass of the drug-containing layer. The transdermal patch prepared by the invention can last for 1-5 days, has a continuous and stable transdermal effect and good safety, effectively improves the compliance and convenience of a patient, and can be used for diminishing inflammation and easing pain caused by osteoarthritis, muscle pain and trauma.

Description

Technical Field

[0001] The invention relates to the technical field of drug-carrying polymer medical preparations, in particular to a transdermal patch based on carbamazepine and a preparation method thereof. Background Art

[0002] As a classic anti-epileptic drug, carbamazepine has shown excellent efficacy in clinical applications. However, the current clinical application of carbamazepine is mostly achieved through oral administration, which is often accompanied by the first-pass effect of the drug in the gastrointestinal tract, resulting in reduced bioavailability, poor patient compliance, and large fluctuations in blood drug concentrations. In addition, oral drugs have a certain impact on the human liver.

[0003] In view of the above problems, the present invention develops a transdermal patch of carbamazepine, which transmits drugs through the transdermal drug delivery system, ensuring that the drug enters the blood circulation system through the skin at a stable and continuous rate, thereby maintaining an effective therapeutic concentration and reducing fluctuations in blood drug concentrations. At the same time, it avoids gastrointestinal discomfort and liver damage that may be caused by oral medication, providing patients with a safer and more effective treatment option. Summary of the invention

[0004] The object of the present invention is to provide a transdermal patch based on carbamazepine and a preparation method thereof, so as to solve the problems in the above-mentioned background technology.

[0005] To achieve the above-mentioned object, the present invention provides the following technical solutions: In a first aspect, the present invention provides a transdermal patch based on carbamazepine, the transdermal patch comprising a drug-containing layer, a backing layer and a protective layer;

[0006] The active ingredient of the drug-containing layer is carbamazepine or a pharmaceutically acceptable salt thereof, and its content accounts for 5% to 35% of the total mass of the drug-containing layer;

[0007] The matrix of the drug-containing layer is composed of one or more of polyvinyl alcohol, acrylic pressure-sensitive adhesive, polybutylene pressure-sensitive adhesive and polysiloxane pressure-sensitive adhesive, and the content of the matrix accounts for 50% to 80% of the total mass of the drug-containing layer.

[0008] Preferably, the drug-containing layer further contains an antioxidant, which is composed of one or more of butylated anisole, tocopherol, and BHT, and the content of the antioxidant accounts for 0.1% to 10% of the total mass of the drug-containing layer.

[0009] Preferably, the active ingredient content of the drug-containing layer accounts for 10% to 30% of the total mass of the drug-containing layer, the matrix content of the drug-containing layer accounts for 60% to 80% of the total mass of the drug-containing layer, and the antioxidant content accounts for 0.1% to 4% of the total mass of the drug-containing layer.

[0010] Preferably, the protective layer is one of a polyethylene release film, a polystyrene release film, a polypropylene release film or a release paper treated with dimethyl silicone oil.

[0011] Preferably, the backing layer is one of polyethylene, polypropylene, polyvinyl chloride, polyamide, polyester, a film of a cellulose derivative synthetic resin, a woven fabric, a knitted fabric, a fiber fabric, or a group consisting of a laminate.

[0012] Preferably, the drug-containing layer further contains a skin permeation enhancer, and the skin permeation enhancer accounts for 0.1% to 15% of the total mass of the drug-containing layer.

[0013] Preferably, the skin penetration enhancer is composed of one or more of glycerol monooleate, glycerol, fatty acid, azone, polyethylene glycol, propylene glycol, butylene glycol, diethylene glycol monoethyl ether, and the skin penetration enhancer accounts for 0.1% to 10% of the total mass of the drug-containing layer.

[0014] Preferably, the transdermal patch further contains an organic solvent for dissolving carbamazepine, and the organic solvent is one or more of ethanol, propylene glycol, acetone, chloroform, dichloromethane, and ethyl acetate.

[0015] Preferably, the drug-containing layer further comprises a filler, and the filler is one or more of polyvinyl pyrrolidone, polyvinyl alcohol, silicon dioxide, bentonite, and talc, and the filler accounts for 0.2% to 5% of the total mass of the drug-containing layer.

[0016] The second aspect of the present invention provides a method for preparing the transdermal patch according to the first aspect of the present invention, comprising the following steps:

[0017] S1, preparation of drug-containing layer:

[0018] The active ingredient is dissolved in an appropriate amount of organic solvent, and then a skin permeation enhancer is added and stirred thoroughly to completely dissolve it, and then a filler, an antioxidant and a matrix are added and stirred to obtain a uniform drug-containing layer;

[0019] S2, preparation of transdermal patch:

[0020] The drug-containing layer is coated on the protective layer, dried at 40°C-60°C for 15 minutes to remove the organic solvent, covered with a backing layer after drying, and then cut into patches of the required size to obtain a transdermal patch.

[0021] The present invention has at least the following beneficial effects:

[0022] The present invention provides a carbamazepine-based transdermal patch and a preparation method thereof. The prepared transdermal patch can last for 1 to 5 days, has a sustained and stable transdermal effect, has good safety, effectively improves patient compliance and convenience, and can be used for the treatment of osteoarthritis, muscle pain, and anti-inflammatory and analgesic effects of swelling and pain caused by trauma. DETAILED DESCRIPTION

[0023] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0024] The present invention provides a carbamazepine-based transdermal patch, which comprises a drug-containing layer, a backing layer and a protective layer;

[0025] The active ingredient of the drug-containing layer is carbamazepine or a pharmaceutically acceptable salt thereof, and its content accounts for 5% to 35% of the total mass of the drug-containing layer, preferably 10% to 30%;

[0026] The matrix of the drug-containing layer is composed of one or more of polyvinyl alcohol, acrylic pressure-sensitive adhesive, polybutylene pressure-sensitive adhesive, and polysiloxane pressure-sensitive adhesive, preferably acrylic pressure-sensitive adhesive, with preferred models of TAK87-4098 and TAK87-2052, and its content accounts for 50% to 80% of the total mass of the drug-containing layer, preferably 60% to 80%.

[0027] Furthermore, the drug-containing layer also contains an antioxidant, which is composed of one or more of butylated anisole, tocopherol, and BHT, preferably BHT, and the content of the antioxidant accounts for 0.1% to 10% of the total mass of the drug-containing layer, preferably 0.1% to 4%.

[0028] Furthermore, the protective layer is one of a polyethylene release film, a polystyrene release film, a polypropylene release film or a release paper treated with dimethyl silicone oil, preferably a polyethylene release film.

[0029] Furthermore, the backing layer is one of polyethylene, polypropylene, polyvinyl chloride, polyamide, polyester, cellulose derivative synthetic resin films, woven fabrics, knitted fabrics, fiber fabrics, or a group consisting of laminates, preferably a polyamide film.

[0030] Furthermore, the drug-containing layer also contains a skin penetration enhancer, which is composed of one or more of glycerol monooleate, glycerol, fatty acid, azone, polyethylene glycol, propylene glycol, butylene glycol, and diethylene glycol monoethyl ether, preferably a combination of diethylene glycol monoethyl ether and glycerol monooleate. The skin penetration enhancer accounts for 0.1% to 15% of the total mass of the drug-containing layer, preferably 1% to 10%.

[0031] Furthermore, the transdermal patch also contains an organic solvent for dissolving carbamazepine, and the organic solvent is one or more of ethanol, propylene glycol, acetone, chloroform, dichloromethane, and ethyl acetate, preferably ethanol.

[0032] Furthermore, the drug-containing layer further comprises a filler, which is one or more of polyvinyl pyrrolidone, polyvinyl alcohol, silicon dioxide, bentonite, and talc. The filler accounts for 0.2% to 5% of the total mass of the drug-containing layer, preferably 0.5% to 2%.

[0033] The preparation method of the transdermal patch comprises the following steps:

[0034] S1, preparation of drug-containing layer:

[0035] The active ingredient is dissolved in an appropriate amount of organic solvent, and then a skin permeation enhancer is added and stirred thoroughly to completely dissolve it, and then a filler, an antioxidant and a matrix are added and stirred to obtain a uniform drug-containing layer;

[0036] S2, preparation of transdermal patch:

[0037] The drug-containing layer is coated on the protective layer, dried at 40°C-60°C for 15 minutes to remove the organic solvent, covered with a backing layer after drying, and then cut into patches of the required size to obtain a transdermal patch.

[0038] Based on the above technical solution, the present invention provides the following partial embodiments:

[0039] Example 1

[0040] Preparation of carbamazepine transdermal patch:

[0041] S1, preparation of drug-containing layer:

[0042] Table 1 Prescription composition and dosage of the drug-containing layer in Example 1

[0043] Component name effect Proportion% Carbamazepine Active ingredients 20 Anhydrous ethanol Solvents Moderate Acrylic pressure sensitive adhesive TAK87-4098 Matrix 68.5 Silicon dioxide Fillers 1 BHT Antioxidants 0.5 Diethylene glycol monoethyl ether Penetration enhancers 5 Glyceryl Monooleate Penetration enhancers 5

[0044] Dissolve carbamazepine in an appropriate amount of ethanol, then add diethylene glycol monoethyl ether and glycerol monooleate, and stir thoroughly to make them completely dissolved; add silicon dioxide, acrylic pressure-sensitive adhesive and BHT, and stir to obtain a uniform drug-containing layer;

[0045] S2, preparation of transdermal patch:

[0046] The drug-containing layer is coated on the protective layer (the protective layer is a polyethylene release film treated with dimethyl silicone oil), dried at 40°C for 15 minutes to remove the organic solvent, and covered with a backing layer (the backing layer is a synthetic resin film of polyethylene, polypropylene and polyvinyl chloride) after drying, and then cut into patches of the required size to obtain a carbamazepine transdermal patch.

[0047] Example 2

[0048] Preparation of carbamazepine transdermal patch:

[0049] S1, preparation of drug-containing layer:

[0050] Table 2 Prescription composition and dosage of the drug-containing layer in Example 2

[0051]

[0052]

[0053] Prepare the drug-containing layer according to the components in the above table, and the remaining steps are the same as in Example 1; S2, the same as in Example 1.

[0054] Example 3

[0055] Preparation of carbamazepine transdermal patch:

[0056] S1, preparation of drug-containing layer:

[0057] Table 3 Prescription composition and dosage of the drug-containing layer in Example 3

[0058] Component name effect Proportion% Carbamazepine Active ingredients 20 Anhydrous ethanol Solvents Moderate Acrylic pressure sensitive adhesive TAK87-4098 Matrix 78.5 Silicon dioxide Fillers 1 BHT Antioxidants 0.5 Diethylene glycol monoethyl ether Penetration enhancers / Glyceryl Monooleate Penetration enhancers /

[0059] Prepare the drug-containing layer according to the components in the above table, and the remaining steps are the same as in Example 1; S2, the same as in Example 1.

[0060] Example 4

[0061] Preparation of carbamazepine transdermal patch:

[0062] S1, preparation of drug-containing layer:

[0063] Table 4 Prescription composition and dosage of the drug-containing layer in Example 4

[0064] Component name effect Proportion% Carbamazepine Active ingredients 20 Anhydrous ethanol Solvents 0 Acrylic pressure sensitive adhesive TAK87-4098 Matrix 68.5 Silicon dioxide Fillers 1 BHT Antioxidants 0.5 Diethylene glycol monoethyl ether Penetration enhancers 5 Glyceryl Monooleate Penetration enhancers 5

[0065] Prepare the drug-containing layer according to the components in the above table, and the remaining steps are the same as in Example 1; S2, the same as in Example 1.

[0066] Example 5

[0067] Preparation of carbamazepine transdermal patch:

[0068] S1, preparation of drug-containing layer:

[0069] Table 5 Prescription composition and dosage of the drug-containing layer in Example 5

[0070] Component name effect Proportion% Carbamazepine Active ingredients 20 Anhydrous ethanol Solvents Moderate Acrylic pressure sensitive adhesive TAK87-2052 Matrix 73.5 Silicon dioxide Fillers 1 BHT Antioxidants 0.5 Diethylene glycol monoethyl ether Penetration enhancers 2.5 Glyceryl Monooleate Penetration enhancers 2.5

[0071] Prepare the drug-containing layer according to the components in the above table, and the remaining steps are the same as in Example 1; S2, the same as in Example 1.

[0072] A series of related tests were conducted on the products prepared in Examples 1 to 5 above, and the results are as follows:

[0073] ①. Physical adhesion:

[0074] Table 6 Physical Adhesion Results

[0075] name Sample preparation Initial adhesion Stickiness Adhesion Example 1 Colorless transparent colloid No. 10 ball >3h 217MN Example 2 Colorless transdermal colloid 8 ball >2.5h 186MN Example 3 Colorless transdermal colloid Ball No. 11 >4.5h 243MN Example 4 Translucent colloid Ball No. 7 >2h 165MN Example 5 Colorless transdermal colloid No. 10 ball >4h 228MN

[0076] It can be seen from the above table that the drug loading and the amount of penetration enhancer have a greater impact on the physical adhesion of the product, and anhydrous ethanol affects the colloid properties during sample preparation; the patch of this product has a longer application time and can be applied for 1 to 2 days.

[0077] ②. Drug release test:

[0078] Using Examples 1 to 5, a drug release test was conducted on pH 7.40 phosphate buffer, and the results are as follows:

[0079] Table 7 Drug release to phosphate buffer

[0080] name Release rate after 48h (%) Example 1 90.5 Example 2 75.1 Example 3 86.2 Example 4 73.4 Example 5 85.4

[0081] It can be seen from the above table that the use of penetration enhancers has no significant effect on the release of the drug, and different concentrations of API will affect the cumulative release of the drug.

[0082] ③. In vitro permeation test of isolated pig skin:

[0083] Using Examples 1, 3, and 5, a drug release test was conducted on a pH 7.40 phosphate buffer solution, and the results were as follows:

[0084] Table 8 Drug skin permeability

[0085] name <![CDATA[Cumulative permeation amount after 48 h (ug / cm 2 )]]> Example 1 895.1 Example 3 465.6 Example 5 659.8

[0086] As can be seen from the above table, transdermal enhancers have a greater impact on drug permeation behavior, and transdermal enhancers need to be added to improve drug permeation.

[0087] The transdermal patch prepared by the present invention can last for 1 to 5 days, has a sustained and stable transdermal effect and good safety, effectively improves the compliance and convenience of patients, and can be used to treat osteoarthritis, muscle pain, and anti-inflammatory and analgesic effects of swelling and pain caused by trauma.

[0088] The above shows and describes the basic principles, main features and advantages of the present invention. It is obvious to those skilled in the art that the present invention is not limited to the details of the above exemplary embodiments, and that the present invention can be implemented in other specific forms without departing from the spirit or basic features of the present invention. Therefore, no matter from which point of view, the embodiments should be regarded as exemplary and non-restrictive. The scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims are included in the present invention.

[0089] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A transdermal patch based on carbamazepine, characterized in that: The transdermal patch comprises a drug-containing layer, a backing layer and a protective layer; The active ingredient of the drug-containing layer is carbamazepine or a pharmaceutically acceptable salt thereof, and its content accounts for 5% to 35% of the total mass of the drug-containing layer; The matrix of the drug-containing layer is composed of one or more of polyvinyl alcohol, acrylic pressure-sensitive adhesive, polybutylene pressure-sensitive adhesive and polysiloxane pressure-sensitive adhesive, and the content of the matrix accounts for 50% to 80% of the total mass of the drug-containing layer.

2. A carbamazepine-based transdermal patch according to claim 1, characterized in that: The drug-containing layer also contains an antioxidant, which is composed of one or more of butylated anisole, tocopherol and BHT, and the content of the antioxidant accounts for 0.1% to 10% of the total mass of the drug-containing layer.

3. A carbamazepine-based transdermal patch according to claim 2, characterized in that: The active ingredient content of the drug-containing layer accounts for 10% to 30% of the total mass of the drug-containing layer, the matrix content of the drug-containing layer accounts for 60% to 80% of the total mass of the drug-containing layer, and the antioxidant content accounts for 0.1% to 4% of the total mass of the drug-containing layer.

4. A carbamazepine-based transdermal patch according to claim 1, characterized in that: The protective layer is one of a polyethylene release film, a polystyrene release film, a polypropylene release film or a release paper treated with dimethyl silicone oil.

5. A carbamazepine-based transdermal patch according to claim 1, characterized in that: The backing layer is one of polyethylene, polypropylene, polyvinyl chloride, polyamide, polyester, cellulose derivative synthetic resin films, woven fabrics, knitted fabrics, fiber fabrics, or a group consisting of laminates.

6. A carbamazepine-based transdermal patch according to claim 1, characterized in that: The drug-containing layer also contains a skin penetration enhancer, which accounts for 0.1% to 15% of the total weight of the drug-containing layer.

7. A carbamazepine-based transdermal patch according to claim 6, characterized in that: The skin penetration enhancer is composed of one or more of glycerol monooleate, glycerol, fatty acid, azone, polyethylene glycol, propylene glycol, butylene glycol, and diethylene glycol monoethyl ether, and the skin penetration enhancer accounts for 0.1% to 10% of the total mass of the drug-containing layer.

8. A carbamazepine-based transdermal patch according to claim 1, characterized in that: The transdermal patch also contains an organic solvent for dissolving carbamazepine, and the organic solvent is one or more of ethanol, propylene glycol, acetone, chloroform, dichloromethane, and ethyl acetate.

9. A carbamazepine-based transdermal patch according to claim 1, characterized in that: The drug-containing layer further comprises a filler, which is one or more of polyvinyl pyrrolidone, polyvinyl alcohol, silicon dioxide, bentonite, and talcum powder, and the filler accounts for 0.2% to 5% of the total mass of the drug-containing layer.

10. The method for preparing the transdermal patch according to any one of claims 1 to 9, characterized in that: The following steps are involved: S1, preparation of drug-containing layer: The active ingredient is dissolved in an appropriate amount of organic solvent, and then a skin permeation enhancer is added and stirred thoroughly to completely dissolve it, and then a filler, an antioxidant and a matrix are added and stirred to obtain a uniform drug-containing layer; S2, preparation of transdermal patch: The drug-containing layer is coated on the protective layer, dried at 40°C-60°C for 15 minutes to remove the organic solvent, covered with a backing layer after drying, and then cut into patches of the required size to obtain a transdermal patch.

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