Carbamazepine non-aqueous transdermal absorption patch and preparation method thereof

Abstract

The invention is suitable for the technical field of drug-loaded polymer medical preparations, and provides a carbamazepine non-aqueous transdermal absorption patch and a preparation method thereof, the carbamazepine non-aqueous transdermal absorption patch comprises the following components by mass: 0.5%-10% of carbamazepine, 10%-50% of a matrix, 0.1%-1.5% of an antioxidant, 0.5%-10% of a cosolvent, 0.1%-10% of a penetration enhancer, 5%-70% of a plasticizer, and 10%-70% of a tackifier; preferably, the carbamazepine tablet comprises the following components in percentage by mass: 1%-5% of carbamazepine, 10%-30% of the matrix, 0.1%-1% of the antioxidant, 1%-5% of the cosolvent, 0.1%-5% of the penetration enhancer, 10%-50% of the plasticizer and 10%-50% of the tackifier. The prepared patch is convenient and safe to use, the compliance of a patient is greatly improved, the drug release rate is high, the oral absorption rate of carbamazepine is increased, the drug effect is stable, and clinical requirements are met.

Description

Technical Field

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

[0002] Carbamazepine (Carbamazepine) is also known as carbamazepine, carbamazepine, carbamazepine, carbamazepine, carbamazepine, carbamazepine, carbamazepine, carbamazepine, carbamazepine, carbamazepine, a common psychotropic drug. It mainly has anti-epileptic effects, and is most effective for psychomotor seizures, and is also effective for grand mal seizures, localized seizures and mixed epilepsy; it is particularly suitable for alleviating mental abnormalities and epilepsy with mental symptoms; it is more effective than intulinum for trigeminal neuralgia and glossopharyngeal neuralgia, has anti-diuretic effects, and can prevent or treat manic depression and anti-arrhythmia.

[0003] Most of the existing carbamazepine is taken orally, but carbamazepine is slowly absorbed orally, which affects the efficacy, and there are certain risks in oral administration. Summary of the invention

[0004] The present invention aims to provide a carbamazepine non-aqueous transdermal absorption patch and a preparation method thereof, so as to solve the problems in the above-mentioned background technology.

[0005] To achieve the above object, the present invention provides the following technical solutions: In a first aspect, the present invention provides a carbamazepine non-aqueous transdermal absorption patch, wherein the components and mass percentages are:

[0006] Carbamazepine 0.5% to 10%, base 10% to 50%, antioxidant 0.1% to 1.5%, cosolvent 0.5% to 10%, penetration enhancer 0.1% to 10%, plasticizer 5% to 70%, and viscosity enhancer 10% to 70%.

[0007] Preferably, the mass percentage of each component is:

[0008] Carbamazepine 1% to 5%, base 10% to 30%, antioxidant 0.1% to 1%, solubilizer 1% to 5%, penetration enhancer 0.1% to 5%, plasticizer 10% to 50%, and viscosity enhancer 10% to 50%.

[0009] Preferably, the co-solvent is one or more of ethanol, acetone, propylene glycol, 1,3-butanediol, isopropanol, and polyethylene glycol.

[0010] Preferably, the matrix is ​​one or more of natural rubber, polyisoprene, styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, styrene-butadiene rubber and polyisobutylene.

[0011] Preferably, the penetration enhancer is one or more of polyethylene glycol, isopropyl myristate, lauric acid, peppermint oil, azone, and propylene glycol.

[0012] Preferably, the antioxidant is one or more of tocopherol, ascorbic acid, butylated hydroxytoluene, and butylated hydroxyanisole.

[0013] Preferably, the plasticizer is one or more of squalane, squalene, liquid paraffin, silicone oil, diethylene glycol, propylene glycol, and crotamiton.

[0014] Preferably, the tackifier is one or more of rosin resin, terpene resin, hydrogenated rosin glycerol ester, alicyclic saturated hydrocarbon resin, and maleic acid resin.

[0015] The second aspect of the present invention provides a method for preparing the non-aqueous transdermal absorption patch of the first aspect, comprising the following steps:

[0016] S1, fully melting and refining the matrix, tackifier, plasticizer and antioxidant at a temperature of 120° C. to 160° C. to obtain a matrix mixture;

[0017] S2, heating and dissolving carbamazepine, a transdermal enhancer, and a cosolvent at a temperature of 100° C. to 120° C. to obtain a bulk drug solution;

[0018] S3, adding the drug substance solution to the matrix mixture, stirring evenly, coating on a silicon-treated PET film, laminating with a polyester cloth, and cutting to a desired size to obtain a non-aqueous transdermal absorption patch.

[0019] The present invention has at least the following beneficial effects:

[0020] The present invention provides a carbamazepine non-aqueous transdermal absorption patch and a preparation method thereof. The prepared patch is convenient and safe to use, greatly improves the compliance of patients, has a fast drug release rate, improves the oral absorption rate of carbamazepine, has stable drug efficacy, and meets clinical needs. DETAILED DESCRIPTION

[0021] 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.

[0022] The present invention provides a carbamazepine non-aqueous transdermal absorption patch, the components and mass percentages of which are as follows:

[0023] Carbamazepine 0.5% to 10%, base 10% to 50%, antioxidant 0.1% to 1.5%, cosolvent 0.5% to 10%, penetration enhancer 0.1% to 10%, plasticizer 5% to 70%, and viscosity enhancer 10% to 70%.

[0024] Furthermore, the mass percentage of each component is:

[0025] Carbamazepine 1% to 5%, base 10% to 30%, antioxidant 0.1% to 1%, solubilizer 1% to 5%, penetration enhancer 0.1% to 5%, plasticizer 10% to 50%, and viscosity enhancer 10% to 50%.

[0026] The cosolvent is one or more of ethanol, acetone, propylene glycol, 1,3-butanediol, isopropanol, and polyethylene glycol, preferably polyethylene glycol.

[0027] The matrix is ​​selected from one or more of natural rubber, polyisoprene, styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, styrene-butadiene rubber and polyisobutylene, preferably styrene-isoprene-styrene block copolymer and polyisobutylene are used together.

[0028] Wherein, the penetration enhancer is selected from at least one of polyethylene glycol, isopropyl myristate, lauric acid, peppermint oil, azone, and propylene glycol, preferably azone and peppermint oil.

[0029] The antioxidant is selected from at least one of tocopherol, ascorbic acid, butylated hydroxytoluene and butylated hydroxyanisole, preferably butylated hydroxytoluene.

[0030] Wherein, the plasticizer is selected from at least one of squalane, squalene, liquid paraffin, silicone oil, diethylene glycol, propylene glycol, and crotamiton, preferably liquid paraffin.

[0031] The tackifier is selected from at least one of rosin resin, terpene resin, alicyclic saturated hydrocarbon resin and maleic acid resin, preferably rosin resin, more preferably hydrogenated rosin glycerol ester and alicyclic saturated hydrocarbon resin. These tackifiers can be used alone or in combination.

[0032] The preparation method of the non-aqueous transdermal absorption patch comprises the following steps:

[0033] S1, fully melting and refining the matrix, tackifier, plasticizer and antioxidant at a temperature of 120° C. to 160° C. to obtain a matrix mixture;

[0034] S2, heating and dissolving carbamazepine, a transdermal enhancer, and a cosolvent at a temperature of 100° C. to 120° C. to obtain a bulk drug solution;

[0035] S3, adding the drug substance solution to the matrix mixture, stirring evenly, coating on a silicon-treated PET film, laminating with a polyester cloth, and cutting to a desired size to obtain a non-aqueous transdermal absorption patch.

[0036] Based on the above technical solution, the present invention provides the following partial embodiments:

[0037] Example 1

[0038] The samples were prepared according to the recipe in Table 1 as follows:

[0039] Table 1 Prescription composition and dosage in Example 1

[0040] Component name effect Proportion% Carbamazepine Active ingredients 3 Styrene-isoprene-styrene block copolymer Matrix 20 Polyisobutylene Matrix 5 Alicyclic saturated hydrocarbon resin Tackifier 30 Liquid paraffin Plasticizers 36.5 Azone Skin penetration enhancers 2 Butylated Hydroxytoluene Antioxidants 0.5 Polyethylene glycol Solvent 3

[0041] Preparation process:

[0042] At a temperature of 120°C, styrene-isoprene-styrene block copolymer, polyisobutylene, hydrogenated rosin glycerol ester, liquid paraffin and butylated hydroxytoluene are fully melted and refined; at a temperature of 100°C, carbamazepine, azone and polyethylene glycol are heated and dissolved; the raw material drug solution is added to the matrix, stirred evenly, coated on a silicon-treated PET film, laminated with a polyester cloth, and cut into a required size to obtain a non-aqueous transdermal absorption patch.

[0043] Example 2

[0044] Table 2 Prescription composition and dosage in Example 2

[0045] Component name effect Proportion% Carbamazepine Active ingredients 3 Styrene-isoprene-styrene block copolymer Matrix 22.5 Polyisobutylene Matrix 7.5 Glycerol Ester of Hydrogenated Rosin Tackifier 20 Liquid paraffin Plasticizers 41.5 peppermint Skin penetration enhancers 2 Butylated Hydroxytoluene Antioxidants 0.5 Polyethylene glycol Solvent 3

[0046] Preparation process:

[0047] At a temperature of 130°C, styrene-isoprene-styrene block copolymer, polyisobutylene, hydrogenated rosin glycerol ester, liquid paraffin and butylated hydroxytoluene are fully melted and refined; at a temperature of 110°C, carbamazepine, peppermint oil and polyethylene glycol are heated and dissolved; the raw material drug solution is added to the matrix, stirred evenly, coated on a silicon-treated PET film, laminated with a polyester cloth, and cut into a required size to obtain a non-aqueous transdermal absorption patch.

[0048] Example 3

[0049] Table 3 Prescription composition and dosage in Example 3

[0050]

[0051]

[0052] Preparation process:

[0053] At a temperature of 140°C, styrene-isoprene-styrene block copolymer, polyisobutylene, hydrogenated rosin glycerol ester, liquid paraffin and butylated hydroxytoluene are fully melted and refined; at a temperature of 120°C, carbamazepine, peppermint oil and polyethylene glycol are heated and dissolved; the raw material drug solution is added to the matrix, stirred evenly, coated on a silicon-treated PET film, laminated with a polyester cloth, and cut into a required size to obtain the non-aqueous transdermal absorption patch of the present invention.

[0054] Example 4

[0055] Table 4 Prescription composition and dosage in Example 4

[0056] Component name effect Proportion% Carbamazepine Active ingredients 3 Styrene-isoprene-styrene block copolymer Matrix 22.5 Polyisobutylene Matrix 10 Glycerol Ester of Hydrogenated Rosin Tackifier 13 Liquid paraffin Plasticizers 48 peppermint Skin penetration enhancers / Butylated Hydroxytoluene Antioxidants 0.5 Polyethylene glycol Solvent 3

[0057] Preparation process:

[0058] At a temperature of 150° C., styrene-isoprene-styrene block copolymer, polyisobutylene, hydrogenated rosin glycerol ester, liquid paraffin and butylated hydroxytoluene are fully melted and refined; at a temperature of 100° C., carbamazepine, peppermint oil and polyethylene glycol are heated and dissolved; the raw material drug solution is added to the matrix, stirred evenly, coated on a silicon-treated PET film, laminated with a polyester cloth, and cut into a required size to obtain the non-aqueous transdermal absorption patch of the present invention.

[0059] Example 5

[0060] Table 5 Prescription composition and dosage in Example 5

[0061] Component name effect Proportion% Carbamazepine Active ingredients 5 Styrene-isoprene-styrene block copolymer Matrix 22.5 Polyisobutylene Matrix 10 Glycerol Ester of Hydrogenated Rosin Tackifier 13 Liquid paraffin Plasticizers 47 peppermint Skin penetration enhancers 2 Butylated Hydroxytoluene Antioxidants 0.5 Polyethylene glycol Solvent /

[0062] Preparation process:

[0063] At a temperature of 160° C., styrene-isoprene-styrene block copolymer, polyisobutylene, hydrogenated rosin glycerol ester, liquid paraffin and butylated hydroxytoluene are fully melted and refined; at a temperature of 120° C., carbamazepine, peppermint oil and polyethylene glycol are heated and dissolved; the raw material drug solution is added to the matrix, stirred evenly, coated on a silicon-treated PET film, laminated with a polyester cloth, and cut into a required size to obtain the non-aqueous transdermal absorption patch of the present invention.

[0064] A series of related tests were performed on the products prepared in the above Examples 1-5, and the results are as follows:

[0065] ①. Physical adhesion

[0066] Table 6 Physical Adhesion Results

[0067]

[0068]

[0069] It can be seen from the above table that the amount of tackifier and matrix used has a great influence on the physical adhesion of the product.

[0070] ②Drug release test

[0071] Using Examples 3, 4, and 5, a drug release test was conducted on pH 7.40 phosphate buffer, and the results were as follows:

[0072] Table 7 Drug release rate to phosphate buffer

[0073] name Release rate after 24 hours (%) Example 3 85.46 Example 4 83.12 Example 5 50.23

[0074] As can be seen from the above table, the use of transdermal enhancement has no significant effect on the drug release rate. In order to increase the drug release rate, a co-solvent needs to be added to increase drug dissolution and further improve the drug release rate.

[0075] ③. In vitro permeation test of isolated pig skin

[0076] Using Examples 3 and 4, a drug release test was conducted on pH 7.40 phosphate buffer, and the results are as follows:

[0077] Table 8 Drug skin permeability

[0078]

[0079] As can be seen from the above table, transdermal enhancers have a greater impact on drug permeability, and transdermal enhancers need to be added to improve drug permeability.

[0080] In summary, the patch prepared by the present invention can be easily applied or removed, is convenient and safe to use, greatly improves patient compliance, has stable drug efficacy, and meets clinical needs. In addition, the drug release rate is fast, which improves the oral absorption rate of carbamazepine.

[0081] 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.

[0082] 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 carbamazepine non-aqueous transdermal patch, characterized in that: The components and mass percentages are: Carbamazepine 0.5% to 10%, base 10% to 50%, antioxidant 0.1% to 1.5%, cosolvent 0.5% to 10%, penetration enhancer 0.1% to 10%, plasticizer 5% to 70%, and viscosity enhancer 10% to 70%.

2. A carbamazepine non-aqueous transdermal patch according to claim 1, characterized in that: The mass percentage of each component is: Carbamazepine 1% to 5%, base 10% to 30%, antioxidant 0.1% to 1%, solubilizer 1% to 5%, penetration enhancer 0.1% to 5%, plasticizer 10% to 50%, and viscosity enhancer 10% to 50%.

3. A carbamazepine non-aqueous transdermal patch according to claim 1, characterized in that: The co-solvent is one or more of ethanol, acetone, propylene glycol, 1,3-butanediol, isopropanol, and polyethylene glycol.

4. The non-aqueous carbamazepine transdermal patch according to claim 1, characterized in that: The matrix is ​​one or more of natural rubber, polyisoprene, styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, styrene-butadiene rubber and polyisobutylene.

5. The non-aqueous carbamazepine transdermal patch according to claim 1, characterized in that: The penetration enhancer is one or more of polyethylene glycol, isopropyl myristate, lauric acid, peppermint oil, azone, and propylene glycol.

6. The non-aqueous carbamazepine transdermal patch according to claim 1, characterized in that: The antioxidant is one or more of tocopherol, ascorbic acid, butylated hydroxytoluene and butylated hydroxyanisole.

7. The non-aqueous transdermal patch for carbamazepine according to claim 1, characterized in that: The plasticizer is one or more of squalane, squalene, liquid paraffin, silicone oil, diethylene glycol, propylene glycol, and crotamiton.

8. The non-aqueous carbamazepine transdermal patch according to claim 1, characterized in that: The tackifier is one or more of rosin resin, terpene resin, hydrogenated rosin glycerol ester, alicyclic saturated hydrocarbon resin, and maleic acid resin.

9. The method for preparing the non-aqueous transdermal patch according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1, fully melting and refining the matrix, tackifier, plasticizer and antioxidant at a temperature of 120° C. to 160° C. to obtain a matrix mixture; S2, heating and dissolving carbamazepine, a transdermal enhancer, and a cosolvent at a temperature of 100° C. to 120° C. to obtain a bulk drug solution; S3, adding the raw material drug solution to the matrix mixture, stirring evenly, coating on a silicon-treated PET film, laminating with a polyester cloth, and cutting to a desired size to obtain a non-aqueous transdermal absorption patch.

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