Defoaming agent and application thereof in preparation process of non-aqueous transdermal system patch

Abstract

The invention relates to the technical field of traditional Chinese medicine external preparations, in particular to a defoaming agent and application thereof in the preparation process of a non-water transdermal system patch. The defoaming agent provided by the invention is obtained by mixing silicon dioxide and liquid paraffin according to a specific ratio and then heating. The silicon dioxide is used as a main defoaming component, and the liquid paraffin is helpful for uniformly dispersing the silicon dioxide in the hot melt colloid and enhancing the fluidity of the silicon dioxide, so that the breakage and discharge of bubbles are promoted, and the problem that the constitution of the paste is changed or the viscosity is reduced due to the addition of the defoaming agent is avoided. In a final non-aqueous transdermal system patch formula, a certain adding amount of the defoaming agent is controlled, so that bubbles can be effectively eliminated, and adverse effects on other physicochemical properties of the patch are avoided. According to the technical scheme, the technical problem that a large amount of foam is generated and is difficult to remove when the hot melt adhesive transdermal patch is subjected to adhesive melting, stirring and mixing operation under the high-temperature condition can be solved, and the hot melt adhesive transdermal patch has ideal popularization and application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of external Chinese medicine preparations, and in particular to a defoaming agent and an application thereof in the preparation process of a non-aqueous transdermal system patch. Background Art

[0002] Non-aqueous transdermal patches are transdermal drug delivery formulations using a non-aqueous solvent (such as oils, alcohols, and esters) as a matrix or dispersion medium. Compared to traditional aqueous transdermal patches, these patches contain no or only a small amount of water. They primarily dissolve or disperse the drug through the non-aqueous phase, delivering it to the body via skin permeation, achieving local or systemic therapeutic effects. As an innovative drug delivery system, non-aqueous transdermal patches deliver drugs through the skin, allowing them to enter the bloodstream or local tissues for action, providing patients with a non-invasive, continuous, and stable treatment option. These patches are known for their unique water-free nature and typically utilize organic solvents or polymers as matrices. They are particularly suitable for drugs that are lipid-soluble or have good transdermal permeability. This design not only improves drug stability but also enhances their ability to penetrate the skin, thereby enhancing therapeutic efficacy.

[0003] Among the many non-aqueous transdermal systems, hot-melt adhesive transdermal patches have attracted considerable attention due to their simple manufacturing process and lack of solvents. Hot-melt adhesive transdermal patches are transdermal drug delivery systems based on hot-melt adhesive (HMA). Hot-melt adhesive is a polymer material that forms an adhesive layer upon application in a molten state and solidifies upon cooling. Its production process is simple, solvent-free, environmentally friendly, and suitable for continuous production. However, during actual production, particularly during melting and mixing operations at high temperatures, the generation of excessive foam is a common problem. Due to the inherent viscosity of hot-melt adhesives, trapped gases are difficult to remove, and even vacuum treatment cannot completely eliminate these bubbles. Consequently, the final adhesive applied to the patch contains bubbles, severely impacting the patch's appearance quality and the accuracy of the drug coating. These issues have significantly limited the industrialization of hot-melt adhesive transdermal patches and negatively impacted the product's market competitiveness. Therefore, it is urgent to develop an effective solution to overcome the problem of easy bubble generation encountered in the production process of hot melt adhesive transdermal patches, improve product quality and production efficiency, and promote the widespread application of such preparations. Summary of the Invention

[0004] The present invention aims to provide an application of a defoaming agent in the preparation of a non-aqueous transdermal system patch to solve the technical problem that a large amount of foam is generated and difficult to eliminate during the melting and stirring mixing operations of hot melt adhesive transdermal patches under high temperature conditions.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions: The invention discloses an application of a defoaming agent in a non-aqueous transdermal system patch. The defoaming agent is obtained by mixing silicon dioxide and liquid paraffin and then subjecting the mixture to a heating treatment.

[0006] Furthermore, the mass ratio of silicon dioxide to liquid paraffin is 1:7-10.

[0007] Furthermore, the temperature of the heating treatment is 110-140° C., and the duration is ≥1 hour; preferably, the heating treatment duration is 1-3 hours.

[0008] Furthermore, the non-aqueous transdermal system patch comprises 20 to 100 parts of a drug component, 350 to 550 parts of a colloid part, 363 to 442 parts of a plasticizer, 80 to 150 parts of a viscosity increasing agent, 2 to 5 parts of a transdermal enhancer, 3 to 6 parts of an antioxidant, 10 to 20 parts of a pH adjusting agent, and 3 to 6 parts of a defoaming agent based on the mass of silicon dioxide; Preferably, the non-aqueous transdermal system patch comprises 40-50 parts of a drug ingredient, 370-390 parts of a colloid part, 370-420 parts of a plasticizer, 125-140 parts of a viscosity increasing agent, 2-5 parts of a transdermal enhancer, 3-6 parts of an antioxidant, 10-20 parts of a pH adjusting agent, and 3-6 parts of a defoaming agent based on the mass of silicon dioxide.

[0009] Furthermore, the drug component includes a nonsteroidal anti-inflammatory drug; the colloid portion includes at least one of an ABA type block copolymer and polyisobutylene; Preferably, the pharmaceutical ingredients include at least one of loxoprofen and its sodium salt, ketoprofen, ibuprofen, aflotoprofen, flurbiprofen, diclofenac and its sodium salt, indomethacin and celecoxib; Preferably, the ABA type block copolymer includes at least one of styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene, styrene-isoprene-styrene, styrene-ethylene / butylene-styrene, and styrene-ethylene / propylene-styrene.

[0010] Furthermore, the plasticizer includes at least one of liquid paraffin, glycerol, and propylene glycol; The tackifier comprises at least one of hydrogenated rosin glycerol ester, terpene resin, and rosin; The transdermal enhancer includes at least one of menthol and L-menthol; The antioxidant includes at least one of butylated hydroxyanisole and butylated hydroxytoluene; The pH adjuster includes at least one of phosphoric acid, acetic acid and citric acid.

[0011] Furthermore, a defoaming agent is used in a non-aqueous transdermal patch, and the application method includes the following steps performed in sequence: S1: The colloid part, the tackifier, and part of the plasticizer are mixed at a temperature of 130-150°C and a rotation speed of 20-30 rpm until melted, and then kneaded for 1-2 hours; after cooling to 115-125°C, a mixture A is obtained; S2: mixing the drug component, the transdermal enhancer, the antioxidant, the pH adjuster and the remaining plasticizer, and homogenizing the mixture to obtain a mixture B; S3: adding the defoaming agent and the mixture B to the mixture A, and refining them at a temperature of 115-125° C. and a speed of 20-30 rpm for 1-1.5 hours to obtain a refined mixture C; S4: coating the mixture C on a carrier to obtain a non-aqueous transdermal system patch.

[0012] This technical solution also provides a defoaming agent for the preparation of hot melt adhesive patches, the raw materials of which include silicon dioxide and liquid paraffin; Preferably, the defoaming agent is prepared by the following method: silicon dioxide and liquid paraffin are mixed in a ratio of 1:7-10, and then heated at 110-140° C. for ≥1 hour to obtain the defoaming agent.

[0013] Furthermore, the silicon dioxide is silicon dioxide prepared by a precipitation method or silicon dioxide prepared by a vapor phase method; Preferably, the silicon dioxide is prepared by a gas phase method; the particle size of the silicon dioxide is in the range of 5 to 40 nm and the specific surface area is in the range of 100 to 400 m 2 / g.

[0014] The present technical solution also provides a method for preparing a non-aqueous transdermal system patch with reduced bubble content, comprising the following steps in sequence: S1: The colloid part, the tackifier, and part of the plasticizer are mixed at a temperature of 130-150°C and a rotation speed of 20-30 rpm until melted, and then kneaded for 1-2 hours; after cooling to 115-125°C, a mixture A is obtained; S2: mixing the drug component, the transdermal enhancer, the antioxidant, the pH adjuster and the remaining plasticizer, and homogenizing the mixture to obtain a mixture B; S3: adding the defoaming agent and the mixture B to the mixture A, and refining them at a temperature of 115-125° C. and a speed of 20-30 rpm for 1-1.5 hours to obtain a refined mixture C; The defoaming agent is prepared by the following method: taking silicon dioxide and liquid paraffin in a mass ratio of 1:7-10, stirring at a temperature of 110°C-140°C and a speed of 20-30 rpm for 1-3 hours to obtain the defoaming agent; S4: coating the mixture C on a carrier to obtain a non-aqueous transdermal system patch; Preferably, the formula of the non-aqueous transdermal system patch is as follows, in parts by weight: 20-100 parts of the drug component, 350-550 parts of the colloid part, 363-442 parts of the plasticizer, 80-150 parts of the viscosity increasing agent, 2-5 parts of the transdermal enhancer, 3-6 parts of the antioxidant, 10-20 parts of the pH adjusting agent, and 3-6 parts of the defoaming agent calculated on the mass of the silicon dioxide; Preferably, the pharmaceutical ingredient comprises a nonsteroidal anti-inflammatory drug; the colloid portion comprises at least one of an ABA-type block copolymer and polyisobutylene; the plasticizer comprises at least one of liquid paraffin, glycerol, and propylene glycol; the tackifier comprises at least one of hydrogenated rosin glycerol ester, terpene resin, and rosin; the transdermal enhancer comprises at least one of menthol and L-menthol; the antioxidant comprises at least one of butylated hydroxyanisole and butylated hydroxytoluene; and the pH adjuster comprises at least one of phosphoric acid, acetic acid, and citric acid. Preferably, the amount of plasticizer used in step S1 is 100-200 parts.

[0015] The technical principle of this technical solution is: This invention provides a novel defoaming agent and its use in the preparation of non-aqueous transdermal patches. This invention aims to address the technical problem of large amounts of foam generated and difficult to remove during the melting and mixing operations of hot-melt adhesive transdermal patches under high temperature conditions. The defoaming agent is obtained by mixing silica and liquid paraffin in a specific ratio and then heating them. This technical solution uses silica as the primary defoaming ingredient because of its large specific surface area and excellent adsorption properties, effectively destabilizing the foam film. Liquid paraffin acts as a carrier, helping to evenly disperse silica in the hot-melt colloid and enhancing its fluidity, thereby promoting the collapse and discharge of bubbles. Experimental results have determined that the optimal mass ratio of silica to liquid paraffin is 1:7-10, which ensures sufficient defoaming effect while avoiding changes in paste texture or loss of viscosity. The mixture is heated at 110-140°C for at least one hour. This step not only helps to increase the dispersion of silica in the liquid paraffin but also further activates its surface activity, improving defoaming efficiency. While some conventional defoamers used in non-aqueous transdermal patch systems can achieve a certain degree of defoaming effect, they can also result in a decrease in the adhesiveness of the patch. The use of the defoamer of this solution and controlled addition amount ensures effective bubble elimination without adversely affecting other physical and chemical properties of the patch.

[0016] The beneficial effects of this technical solution are: The defoaming agent provided by the present invention and its application in the preparation of non-aqueous transdermal system patches bring significant beneficial effects, as follows: (1) High-efficiency defoaming: The unique combination of silica and liquid paraffin can quickly and effectively eliminate bubbles in hot-melt colloids at high temperatures, significantly improving the quality and appearance of the patch. This solution solves the problem of product defects caused by bubbles in traditional methods, reduces the scrap rate, improves the overall efficiency of the production line, and is conducive to promoting the industrialization of non-aqueous transdermal system patches.

[0017] (2) No impact on product performance: The defoaming agent will not change the basic physical and chemical properties of the patch (such as adhesion, etc.) during use, ensuring the stability and efficacy of the product.

[0018] (3) Strong process adaptability: It is suitable for various types of ABA block copolymers, polyisobutylene and other colloidal materials, showing wide applicability.

[0019] In summary, the present invention not only solves the problems existing in the prior art, but also provides a simple and effective solution for the preparation of non-aqueous transdermal system patches, and has important practical application value. DETAILED DESCRIPTION

[0020] The following examples are intended only to more clearly illustrate the technical solutions of the present invention and are therefore provided as examples only and are not intended to limit the scope of protection of the present invention. The specific embodiments listed herein are merely exemplary of the present invention and are not intended to limit the scope of protection of the present invention. For those skilled in the art, any equivalent modifications and substitutions made to the embodiments described below are also within the scope of the present invention. Therefore, equivalent transformations and modifications made without departing from the spirit and scope of the present invention should be encompassed within the scope of the present invention. To better illustrate the present invention, numerous specific details are provided in the following specific embodiments. Those skilled in the art should understand that the present invention can be implemented without certain specific details. In other embodiments, methods, means, equipment, and steps well known to those skilled in the art are not described in detail in order to highlight the main purpose of the present invention. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art. Unless otherwise specified, the units used in this specification are international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0021] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Materials, reagents, or instruments used, for which the manufacturer is not indicated, are commercially available. For any unspecified conditions in the examples, conventional conditions or those recommended by the manufacturer were followed. The present invention does not limit the sources of the raw materials used; unless otherwise specified, the raw materials used in the present invention are commercially available products in the art. Unless otherwise specified, "ratios" in the following examples are by mass.

[0022] Preparation of a new defoaming agent and its application in the preparation of non-aqueous transdermal system patches (1) Preparation of defoaming agent The defoamer used in this solution is made from silicon dioxide, which is processed as follows: silicon dioxide is mixed with liquid paraffin in a mass ratio of 1:7-10, then stirred at 110°C-140°C (20-30 rpm) for 1-3 hours. The defoamer is a mixture of heat-treated silicon dioxide and liquid paraffin. The liquid paraffin meets the quality requirements of the 2020 edition of the Chinese Pharmacopoeia.

[0023] (2) Composition of non-aqueous transdermal patches In parts by weight, the raw materials of the non-aqueous transdermal system patch include 20 to 100 parts (preferably 40 to 50 parts) of the drug component and 350 to 550 parts (preferably 370 to 390 parts) of the colloid part.

[0024] To further improve the performance and quality of the non-aqueous transdermal system patch, the other parts of the non-aqueous transdermal system patch include 363-442 parts (preferably 370-420 parts) of a plasticizer, 80-150 parts (preferably 125-140 parts) of a viscosity enhancer, 2-5 parts of a transdermal enhancer, 3-6 parts of a defoaming agent (based on the mass of silicon dioxide), 3-6 parts of an antioxidant, and 10-20 parts of a pH adjuster.

[0025] Among them, the drug ingredients include non-steroidal anti-inflammatory drugs; further, the drug ingredients include at least one of loxoprofen and its sodium salt, ketoprofen, ibuprofen, iflorfen, flurbiprofen, diclofenac and its sodium salt, indomethacin, and celecoxib.

[0026] The colloid part includes at least one of ABA type block copolymer and polyisobutylene, both of which are conventional colloid materials for preparing non-aqueous transdermal system patches.

[0027] ABA-type block copolymers are a class of polymer materials composed of three different polymer segments: identical polymer segments (A) at both ends and a different type of polymer segment (B) in the middle. This structure imparts unique physical properties, such as those of a thermoplastic elastomer. Preferably, the ABA-type block copolymer includes at least one of styrene-isoprene-styrene block copolymer (SIS), styrene-butadiene-styrene (SBS), styrene-isoprene-styrene (SIS), styrene-ethylene / butylene-styrene (SEBS), and styrene-ethylene / propylene-styrene (SEPS).

[0028] Polyisobutylene (PIB) is a synthetic rubber made from the polymerization of isobutylene monomer. It has excellent airtightness, weather resistance, and electrical insulation properties while remaining flexible over a wide temperature range.

[0029] Plasticizers are used to increase the flexibility and ductility of the polymer, reduce brittleness, and make the patch more comfortable and better fit the skin surface. The plasticizer includes at least one of liquid paraffin, glycerin, and propylene glycol.

[0030] The tackifier is at least one of hydrogenated rosin glycerol ester, terpene resin, rosin, etc.

[0031] Rosin is a natural resin obtained primarily from the sap extracted from the trunk of pine trees.

[0032] Hydrogenated rosin glycerol ester (CAS No. 65997-13-9) is a compound obtained by esterifying rosin with glycerol and then hydrogenating the resulting ester product. It is one of the further processed products of rosin and exhibits excellent thermal stability and antioxidant properties.

[0033] Terpene resin (CAS No.: 9003-74-1) is a type of artificial synthetic resin made by polymerizing terpene compounds (such as pinene, limonene, etc.).

[0034] Transdermal enhancers increase the permeability of the skin, helping drugs to more effectively penetrate the stratum corneum and enter the blood circulation system. The transdermal enhancer is at least one of menthol and L-menthol.

[0035] Antioxidants are used to protect the drug from colloid aging during storage, which can reduce the patch's adhesion and lead to instability during use. Antioxidants include at least one of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT).

[0036] The pH adjuster includes at least one of phosphoric acid, acetic acid, and citric acid.

[0037] In order to eliminate bubbles generated during the preparation process, the defoaming agent prepared in this scheme is further added to the above raw materials. The amount of silicon dioxide is 3-6 parts based on the mass of silicon dioxide in the defoaming agent.

[0038] (3) Preparation of non-aqueous transdermal patches S1 kneading: Add all the colloid part, tackifier and part of the plasticizer (about 100-200 parts of plasticizer) into a double-channel mixer, set the temperature to 130-150°C, heat until completely melted, then knead for 1-2 hours (20-30 rpm), cool to about 120°C (115-125°C can be selected), and maintain this temperature to obtain mixture A.

[0039] Preparation of mixture of S2 drug and other ingredients: The main component (drug component), transdermal enhancer, antioxidant, and pH adjuster are added to the remaining plasticizer and homogenized for 5 to 10 minutes (homogenizer speed 5000 rpm or above) to obtain mixture B.

[0040] S3 refining: Add the defoamer and mixture B to mixture A, maintain the temperature at about 120°C (115-125°C can be selected), and mix in a double-channel mixer at a speed of 20-30 rpm for 1-1.5 hours to obtain mixed mixture C.

[0041] The defoaming agent is prepared by the following method: silicon dioxide and liquid paraffin are taken in proportion, stirred (20-30 rpm) at a temperature of 110-140° C. for 1-3 hours to obtain the defoaming agent.

[0042] S4 coating: The refined mixture C is coated on a polyester film coated with dimethicone oil, which is then attached to a stretch fabric or a knitted fabric, and then cut into patches of corresponding specifications to obtain the product.

[0043] The technical solution of the present invention will be described below with reference to specific embodiments, including: Example 1 The formula of the non-aqueous transdermal system patch used in this embodiment is: The drug ingredients include 50 parts of loxoprofen sodium, 230 parts of styrene-isoprene-styrene block copolymer (SIS) (colloid part), 140 parts of polyisobutylene (colloid part), 370 parts of liquid paraffin (plasticizer), 125 parts of hydrogenated rosin glycerol ester (tackifier), 3 parts of L-menthol (transdermal enhancer), 5 parts of butylated hydroxytoluene (BHT) (antioxidant), 15 parts of phosphoric acid (pH adjuster), and 5 parts of silicon dioxide (i.e., 5 parts of defoaming agent based on the mass of silicon dioxide; the defoaming agent includes silicon dioxide and liquid paraffin in a mass ratio of 1:8).

[0044] Among them, the structural formula of SIS is: -[-CH=CH2-Ph-] n -[CH2-C(CH3)=CH-CH2] m -[-CH=CH2-Ph-] n -; Wherein, Ph represents a benzene ring, n and m represent the degree of polymerization of the styrene block and the isoprene block, respectively, with n ranging from 100 to 500 and m ranging from 300 to 1000. SIS occurs in subsequent examples and comparative examples, and the situation is the same as in this example.

[0045] The molecular weight of polyisobutylene is between 50,000 and 120,000. Polyisobutylene appears in subsequent examples and comparative examples, and the situation is the same as that of this example.

[0046] The silicon dioxide is prepared by precipitation method (precipitated silica) or fumed silica (fumed silica). Both of the above silicon dioxides can be obtained through commercial means. The silicon dioxide prepared by precipitation method and the silicon dioxide prepared by fumed silica are conventional products in the prior art. This embodiment specifically uses the silicon dioxide prepared by fumed silica, with a particle size range of 5-40nm and a specific surface area of ​​100-400m 2 The subsequent examples and comparative examples contain silicon dioxide, and the situation is the same as that of this example.

[0047] The hydrogenated rosin glycerol ester may be KE-311 type. The subsequent examples and comparative examples contain hydrogenated rosin glycerol ester, and the situation is the same as that of this example.

[0048] The preparation method is as follows: S1 kneading: Styrene-isoprene-styrene block copolymer (SIS), hydrogenated rosin glycerol ester, polyisobutylene, and about 185 parts of liquid paraffin were added to a double-channel mixer, set to 140°C, heated until completely melted, and then kneaded for 1.5 hours (25 rpm), cooled to about 120°C, and maintained at this temperature to obtain mixture A.

[0049] Preparation of mixture of S2 drug and other ingredients: Loxoprofen sodium, L-menthol, butylated hydroxytoluene, and phosphoric acid are added to the remaining approximately 185 parts of liquid paraffin, and homogenized for 8 minutes (homogenizer speed of 5000 rpm or above) to obtain mixture B.

[0050] S3 refining: Add the defoamer and mixture B to mixture A, maintain the temperature at about 120°C, rotate the double-channel mixer at 25 rpm, and blend for 1.5 hours to obtain blended mixture C.

[0051] The defoaming agent was prepared by the following method: silicon dioxide and liquid paraffin (1:8) were mixed at 130° C. and stirred (25 rpm) for 2 hours to obtain the defoaming agent.

[0052] S4 coating: The refined mixture C is coated on a polyester film coated with dimethicone oil, which is then attached to a stretch fabric or a knitted fabric, and then cut into patches of corresponding specifications.

[0053] The mixture C and the patch obtained in this example were experimentally studied. For details, see the experimental results of Experimental Examples 1 and 2.

[0054] Example 2 The formula of the non-aqueous transdermal system patch used in this embodiment is: The drug ingredients include 40 parts of flurbiprofen, 250 parts of styrene-isoprene-styrene block copolymer (SIS) (colloid part), 140 parts of polyisobutylene (colloid part), 420 parts of liquid paraffin (plasticizer), 140 parts of terpene resin (tackifier), 3 parts of L-menthol (transdermal enhancer), 5 parts of butylated hydroxytoluene (BHT) (antioxidant), 15 parts of phosphoric acid (pH adjuster), and 5 parts of silicon dioxide (i.e., 5 parts of defoaming agent based on the mass of silicon dioxide; the defoaming agent includes silicon dioxide and liquid paraffin in a mass ratio of 1:7).

[0055] Terpene resins may include α-pinene resin, β-pinene resin, limonene resin, and the like. Specifically, limonene resin is used in this embodiment. It is a terpene thermoplastic resin produced by polymerization of the natural monomer limonene, with a molecular weight of 800-1500. Terpene resins are used in subsequent embodiments and comparative examples, and the conditions are the same as in this embodiment.

[0056] The preparation method is as follows: S1 kneading: Styrene-isoprene-styrene block copolymer (SIS), terpene resin, polyisobutylene and an appropriate amount of liquid paraffin (about 185 parts) were added to a double-channel mixer, the temperature was set to 130°C, and the mixture was heated until completely melted. The mixture was then kneaded for 1 hour (30 rpm), cooled to about 120°C, and maintained at this temperature to obtain mixture A.

[0057] Preparation of mixture of S2 drug and other ingredients: Flurbiprofen, L-menthol, butylated hydroxytoluene, and phosphoric acid were added to the remaining portion of liquid paraffin and homogenized for 5 minutes (homogenizer speed 5000 rpm or above) to obtain mixture B.

[0058] S3 refining: Add the defoamer and mixture B to mixture A, maintain the temperature at about 120°C, rotate the double-channel mixer at 25 rpm, and blend for 1.5 hours to obtain blended mixture C.

[0059] The defoaming agent was prepared by the following method: silicon dioxide and liquid paraffin (1:7) were mixed at 110° C. and stirred (30 rpm) for 3 hours to obtain the defoaming agent.

[0060] S4 coating: The refined mixture C is coated on a polyester film coated with dimethicone oil, which is then attached to a stretch fabric or a knitted fabric, and then cut into patches of corresponding specifications.

[0061] The mixture C and the patch obtained in this example were experimentally studied. For details, see the experimental results of Experimental Examples 1 and 2.

[0062] Example 3 The formula of the non-aqueous transdermal system patch used in this embodiment is: The drug ingredients include 40 parts of afluprofen, 230 parts of styrene-isoprene-styrene block copolymer (SIS) (colloid part), 140 parts of polyisobutylene (colloid part), 405 parts of liquid paraffin (plasticizer), 130 parts of hydrogenated rosin glycerol ester (tackifier), 3 parts of L-menthol (transdermal enhancer), 5 parts of butylated hydroxytoluene (BHT) (antioxidant), 15 parts of phosphoric acid (pH adjuster), and 5 parts of silicon dioxide (i.e., 5 parts of defoaming agent calculated by the mass of silicon dioxide; the defoaming agent includes silicon dioxide and liquid paraffin in a mass ratio of 1:10).

[0063] The preparation method is as follows: S1 kneading: Styrene-isoprene-styrene block copolymer (SIS), hydrogenated rosin glycerol ester, polyisobutylene, and an appropriate amount of liquid paraffin (about 185 parts) were added to a double-channel mixer, set to 150°C, heated until completely melted, and then kneaded for 1 hour (20 rpm), cooled to about 120°C, and maintained at this temperature to obtain mixture A.

[0064] Preparation of mixture of S2 drug and other ingredients: Add fluoroprofen, L-menthol, butylated hydroxytoluene, and phosphoric acid to the remaining portion of liquid paraffin, and homogenize for 10 minutes (homogenizer speed 5000 rpm or above) to obtain mixture B.

[0065] S3 refining: Add the defoamer and mixture B to mixture A, maintain the temperature at about 120°C, rotate the double-channel mixer at 30 rpm, and blend for 1 hour to obtain a blended mixture C.

[0066] The defoaming agent was prepared by the following method: silicon dioxide and liquid paraffin (1:10) were mixed, stirred (30 rpm) at a temperature of 140° C. for 1 hour to obtain the defoaming agent.

[0067] S4 coating: The refined mixture C is coated on a polyester film coated with dimethicone oil, which is then attached to a stretch fabric or a knitted fabric, and then cut into patches of corresponding specifications.

[0068] The mixture C and the patch obtained in this example were experimentally studied. For details, see the experimental results of Experimental Examples 1 and 2.

[0069] Comparative Example 1 This comparative example is substantially the same as Example 1, except that no defoamer is added to the patch. The formula omits 5 parts of defoamer by weight of silica based on Example 1, and the step of adding the component is omitted in the preparation process. The mixture C obtained in this comparative example includes only mixture B and mixture A. The mixture C and the patch obtained in this comparative example were experimentally studied, and the experimental results of Experimental Examples 1 and 2 are detailed.

[0070] Comparative Example 2 This comparative example is essentially the same as Example 1, except that the defoamer in Example 1 is replaced with an equal amount of silicon dioxide + vegetable oil, and the silicon dioxide is not treated with liquid paraffin. More specifically, the formulation and preparation process of this comparative example are the same as those of Example 1, except that the defoamer of Example 1 is replaced with an equal amount (based on the mass of silicon dioxide) of the defoamer of this comparative example. The defoamer of this scheme is prepared by combining silicon dioxide and vegetable oil (1:8), stirring at 130°C (25 rpm) for 2 hours to obtain the defoamer. Experimental studies were conducted on the mixture C and patch obtained in this comparative example. See the experimental results of Experimental Examples 1 and 2 for details.

[0071] Comparative Example 3 This comparative example is substantially the same as Example 1, and difference is the preparation method of defoamer, specifically as follows: silicon dioxide and liquid paraffin are mixed according to the mass ratio of 1: 8, then room temperature is placed for 3h, to obtain. In this comparative example, the mixture of silicon dioxide and liquid paraffin is not heat-treated. The mixture C and patch obtained by this comparative example are experimentally studied, see the experimental result of experimental example 1 and experimental example 2 for details.

[0072] Comparative Example 4 This comparative example is essentially the same as Example 1, except that the defoaming agent preparation method is as follows: the ratio of silicon dioxide to liquid paraffin is adjusted to 1:5, and the remaining defoaming agent preparation method is the same as Example 1. Experimental studies were conducted on the mixture C and the patch obtained in this comparative example. For details, see the experimental results of Experimental Examples 1 and 2.

[0073] Comparative Example 5 This comparative example is essentially the same as Example 1, except that the defoaming agent preparation method is as follows: the ratio of silicon dioxide to liquid paraffin is adjusted to 1:12, and the rest of the defoaming agent preparation method is the same as Example 1. Experimental studies were conducted on the mixture C and the patch obtained in this comparative example. See the experimental results of Experimental Examples 1 and 2 for details.

[0074] Comparative Example 6 This comparative example is essentially the same as Example 1, except that the defoaming agent preparation method is as follows: the silica and liquid paraffin are mixed and then treated at a temperature of 90°C. The remaining steps are the same as those for the defoaming agent preparation method of Example 1. Experimental studies were conducted on the mixture C and the patch obtained in this comparative example. For details, see the experimental results of Experimental Examples 1 and 2.

[0075] Comparative Example 7 This comparative example is essentially the same as Example 1, except for the method for preparing the defoamer, specifically, the following: the post-treatment temperature of the silica and liquid paraffin mixture is 160°C. The remaining steps are the same as those for preparing the defoamer in Example 1. Experimental studies were conducted on the mixture C and the patch obtained in this comparative example. For details, see the experimental results of Experimental Examples 1 and 2.

[0076] Comparative Example 8 This comparative example is essentially the same as Example 1, except that an equal amount of liquid paraffin is used in place of the defoaming agent in Example 1. More specifically, the candidate defoaming agent used in this comparative example is 45 parts of liquid paraffin, which is stirred at 25 rpm for 2 hours at 130°C. Experimental studies were conducted on the mixture C and the patch obtained in this comparative example. See the experimental results of Experimental Examples 1 and 2 for details.

[0077] Comparative Example 9 This comparative example is essentially the same as Example 1, except that an equal amount of dimethyl silicone oil is used in place of the defoaming agent in Example 1. More specifically, this comparative example uses 45 parts of dimethyl silicone oil as the candidate defoaming agent, and the dimethyl silicone oil is stirred at 130°C for 2 hours (25 rpm). Experimental studies were conducted on the mixture C and the patch obtained in this comparative example. See the experimental results of Experimental Examples 1 and 2 for details.

[0078] Although dimethyl silicone oil is a defoaming agent in the prior art, in the specific application scenario of this solution, the use of dimethyl silicone oil not only fails to defoam, but also greatly reduces the adhesion of the patch.

[0079] If simethicone emulsion or dimethicone emulsion, which are similar products of the prior art to dimethicone, are used as defoaming agents, although a certain defoaming effect can be achieved, the problem of greatly reduced adhesion of the patch will also occur.

[0080] Comparative Example 10 This comparative example is basically the same as Example 1, except that the defoaming agent is prepared as follows: Silicon dioxide and dimethyl silicone oil were mixed in a mass ratio of 1:8, and then stirred at 130°C (25 rpm) for 2 hours to obtain the mixture. Experimental studies were conducted on the mixture C and the patch obtained in this comparative example. See the experimental results of Experimental Examples 1 and 2 for details. Although the defoaming agent based on silicon dioxide and dimethyl silicone oil prepared in this comparative example achieved a defoaming effect, it also caused a significant reduction in the adhesion of the patch.

[0081] Comparative Example 11 This comparative example is basically the same as Example 1, except that the preparation method of the non-aqueous transdermal system patch is different. Compared with Example 1, the preparation process of the non-aqueous transdermal system patch of this comparative example is adjusted in the "S1 kneading" step and the "S3 refining" step, specifically: S1 Kneading: Add defoamer, styrene-isoprene-styrene block copolymer (SIS), hydrogenated rosin glycerol ester, polyisobutylene, and approximately 185 parts of liquid paraffin to a double-channel mixer. Set the temperature to 140°C and heat until completely melted. Then knead for 1.5 hours (25 rpm). Cool to approximately 120°C and maintain this temperature to obtain Mixture A.

[0082] S3 refining: adding mixture B to mixture A, maintaining the temperature at about 120°C, rotating the double-channel mixer at 25 rpm, and refining for 1.5 hours to obtain a refined mixture C.

[0083] The remaining operating steps are exactly the same as those in Example 1. Experimental studies were conducted on the mixture C and the patch obtained in this comparative example. For details, see the experimental results of Experimental Examples 1 and 2. Mixture A is relatively viscous and theoretically prone to bubbles during heating and stirring. In theory, the defoaming agent should be added at this step. However, the experimental results of this comparative example show that the defoaming effect of adding the defoaming agent of this solution in step S1 is not ideal.

[0084] Comparative Example 12 This comparative example is basically the same as Example 1, except for the preparation method of the non-aqueous transdermal patch. Compared with Example 1, the preparation process of the non-aqueous transdermal patch of this comparative example is adjusted in the "S2 preparation of the mixture of the drug and other ingredients" step and the "S3 refining" step, specifically: Preparation of mixture of S2 drug and other ingredients: Defoaming agent (prepared according to the method of Example 1), loxoprofen sodium, L-menthol, butylated hydroxytoluene, and phosphoric acid were added to the remaining approximately 185 parts of liquid paraffin and homogenized for 8 minutes (homogenizer speed of 5000 rpm or above) to obtain mixture B.

[0085] S3 refining: adding mixture B to mixture A, maintaining the temperature at about 120°C, rotating the double-channel mixer at 25 rpm, and refining for 1.5 hours to obtain a refined mixture C.

[0086] The remaining steps are exactly the same as in Example 1.

[0087] The mixture C and the patch obtained in this example were experimentally studied. For details, see the experimental results of Experimental Examples 1 and 2.

[0088] Experimental Example 1: Defoaming Effect Experiment The mixed colloids (mixture C) prepared in the examples and comparative examples were quickly poured into a pre-prepared mold provided with a backing layer. The size of the mold was 5×5×1 cm. After cooling and solidification, the solidified colloid was taken out (hereinafter referred to as the sample). The sample was observed under a microscope (magnification: 5×5), and the number of bubbles therein was counted (the bubbles observable in the entire plane with an area of ​​5×5 cm were counted). Then, the number of bubbles per square centimeter was calculated (the number of bubbles per square centimeter of each sample was calculated to the nearest single digit. Bubbles were observed and counted for three samples in each example or comparative example), thereby characterizing the defoaming effect of the defoaming agent.

[0089] The identification criteria for bubbles are: a round or nearly round shape with smooth, well-defined edges. Under an optical microscope, they appear as bright, transparent areas with a slightly dark center due to light refraction and distinct reflective bands at the edges. It's important to distinguish bubbles from other structures: unlike impurity particles, bubbles are hollow and transmit light well. Unlike cracks and holes, bubbles are closed and have rounded edges. Impurities are typically irregular in shape, dark in color, or scatter light strongly. See Table 1 for experimental results.

[0090] Table 1: Number of bubbles in Examples and Comparative Examples

[0091] Comparative Example 1 did not add the defoaming agent of the present invention, resulting in more bubbles in the sample, reaching 7 / cm 2 In Examples 1-3, the defoaming agent of silica + liquid paraffin of this solution was used, and the bubbles in the samples were effectively removed, and basically no bubbles were observed in the samples.

[0092] Comparative Example 2: Vegetable oil and silicon dioxide were mixed and heated to obtain a comparative defoamer. However, the bubbles in the sample were still not effectively eliminated, with the number of bubbles reaching 5 / cm. 2 . Comparing Example 1 and Comparative Example 2, it can be seen that silicon dioxide needs to be used in combination with specific substances to obtain an ideal defoaming effect. In addition, the inventors have also tried to add silicon dioxide directly to the preparation process of the non-aqueous transdermal system patch, that is, to use silicon dioxide to replace the defoaming agent of Example 1 (based on the mass of silicon dioxide, an equal replacement is made), and found that the defoaming effect of silicon dioxide alone is slightly worse than that of Comparative Example 2. It can be seen that silicon dioxide alone is not feasible under the application conditions of this scheme. The defoaming agent of Comparative Example 8 contains only liquid paraffin, and the bubble content in the sample is high, indicating that liquid paraffin has no defoaming effect. Liquid paraffin needs to be used in combination with silicon dioxide to achieve an ideal defoaming effect.

[0093] When preparing the defoamer, Comparative Example 3 only mixed liquid paraffin with silicon dioxide without heat treatment. The defoaming effect of the defoamer was also unsatisfactory, and a certain amount of bubbles were present in the sample. The amount of liquid paraffin used in the defoamer of Comparative Example 4 was too low, and the amount of liquid paraffin used in the defoamer of Comparative Example 5 was too high, both of which affected the defoaming effect to varying degrees. The heat treatment temperature of the defoamer of Comparative Example 6 was too low, and the heat treatment temperature of the defoamer of Comparative Example 7 was too high, both of which affected the defoaming effect to varying degrees. This shows that the defoamer of silicon dioxide + liquid paraffin in this solution, the setting of parameters such as the amount ratio of silicon dioxide and liquid paraffin, and the heat treatment temperature, are very critical for the defoaming effect of the defoamer.

[0094] The defoamer in Comparative Example 9 contains only dimethyl silicone oil, which has an unsatisfactory defoaming effect and also causes the problem of decreased patch adhesion (see Experimental Example 2 for adhesion). Comparative Example 10 uses a mixed heat treatment of dimethyl silicone oil and silicon dioxide to obtain a comparative defoamer. The bubbles in the sample are effectively eliminated, but the viscosity of the patch is significantly reduced (see Experimental Example 2 for adhesion), which cannot meet the application requirements. The comparative defoamer obtained by mixing dimethyl silicone oil and silicon dioxide and heating is a conventional defoamer in the prior art and has been reported in the prior art literature. However, when it is used in the non-aqueous transdermal system patch of this scheme, it is found that it has a negative impact on the performance of the patch, making it difficult for the patch to adhere to the medication site, affecting the effect of the drug.

[0095] The process sequence of Comparative Examples 11 and 12 is different from that of Example 1. The defoaming agent of this solution is added through step S1 in Comparative Example 11 and through step S2 in Comparative Example 12. The defoaming effect of the defoaming agent of Comparative Examples 11 and 12 is lower than that of Example 1. In addition, the inventors also tried to add half the amount of defoaming agent in step S1 and half the amount of defoaming agent in step S2. The rest of the operation is the same as in Example 1, and the defoaming effect is basically the same as that of Comparative Example 11. This shows that the defoaming agent of this technical solution is applied to non-aqueous transdermal system patches, and a specific application method is required to fully exert its effect. The process sequence to ensure that the defoaming agent of this solution exerts an ideal effect is: mixing the colloid part, the tackifier and part of the plasticizer to form a mixture A; mixing the drug part, the transdermal enhancer, the antioxidant, the pH regulator and part of the plasticizer to form a mixture B; then, mixing the defoaming agent prepared in this solution with mixtures A and B. The inventors believe this may be because the defoamer's effectiveness relies on its ability to rapidly diffuse at the gas-liquid interface and disrupt the foam structure. Adding it at the wrong time could hinder its effective distribution or activity. By preparing mixtures A and B separately, they create an ideal environment for the defoamer, allowing it to effectively disperse and function in subsequent steps.

[0096] Experimental Example 2: Patch-related index detection (1) Adhesion test This test was carried out in accordance with the first method of General Rules 0952 of Part IV of the 2020 edition of the Chinese Pharmacopoeia. Take the patches prepared in the examples and comparative examples, and fix the adhesive surface of the patches upward on the inclined surface of the adhesion tester. Set the position 10 cm above the inclined surface from the test sample as the center of the ball, and place a steel ball (see General Rules 0952 for the steel ball number and specifications) on this position. Let it fall freely from the inclined surface, and record the number of the largest ball that the adhesive surface can prevent from falling. Repeat the test three times, and record the largest steel ball that the patch can adhere to in the three experiments. Among the steel balls that are adhered to by the three test samples, if all three are the largest steel balls, or two are the largest steel balls and the other steel ball is only one size smaller, it is in compliance with the regulations; if one is the largest steel ball and the other two steel balls are only one size smaller, three more pieces should be taken for retesting, and if all three pieces can adhere to the largest-numbered steel ball, it is in compliance with the regulations.

[0097] The experimental results are shown in Table 2. The parameters of the steel balls involved in the table are as follows: Steel ball No. 19: diameter 12.700 mm, weight per thousand 8.42 kg; Steel ball No. 20: diameter 13.494 mm, weight per thousand 10.1 kg; Steel ball No. 23: diameter 15.875 mm, weight per thousand 16.5 kg; Steel ball No. 28: diameter 19.844 mm, weight per thousand 32.4 kg; Steel ball No. 30: diameter 22.225 mm, weight per thousand 45.2 kg; Steel ball No. 31: diameter 23.019 mm, weight per thousand 50 kg; Steel ball No. 32: diameter 23.8131 mm, weight per thousand 55.5 kg; Steel ball No. 33: diameter 25.400 mm, weight per thousand 57.4 kg.

[0098] (2) Drug content The content of active ingredients in the patch is the basis for ensuring its therapeutic effect.

[0099] Samples from each example and comparative example were taken and the NSAID content in the patch was tested, and the percentage content was calculated. The calculation method is: percentage content = measured amount / labeled amount × 100%, where the measured amount is the actual amount of NSAID measured and the labeled amount is the theoretical amount of NSAID. The experimental results are detailed in Table 2. The experimental results show that the NSAID content in the patch prepared in the embodiment of this solution is relatively ideal, reaching a level of approximately 99%, effectively ensuring its therapeutic effect.

[0100] (3) Thermal stability test The patches prepared in the examples and comparative examples were sealed and placed in a 60°C environment for 10 days. The appearance of the patches was then observed and their adhesion tested. The experimental results are shown in Table 2. The appearance of the patches after storage was observed. The patches of Examples 1-3 appeared to have a liner covering the surface of the paste, and were light brown to brown (paste surface) with a unique aroma.

[0101] Table 2: Adhesion test results

[0102] In Table 2, I means that the sample was tested immediately after preparation without being placed in a 60°C environment for 10 days; E means that the sample was tested after being placed in a 60°C environment for 10 days.

[0103] The experimental results in Table 2 show that the non-aqueous transdermal system patches prepared using the methods of Examples 1-3 exhibited good adhesion, preventing the No. 32 ball from falling, overcoming the problem of reduced patch adhesion caused by the addition of conventional defoaming agents. Furthermore, the patches prepared according to this technical solution exhibited good stability. After 10 days at 60°C, the patches, with the padding covering the paste surface, were observed to be light brown to brown (paste surface) and had a unique aroma. Even after 10 days at 60°C, the patches still prevented the No. 31 ball from falling.

[0104] However, using conventional defoamers from the prior art (Comparative Example 10, a comparative defoamer obtained by mixing dimethyl silicone oil and silica and heating the mixture) or using dimethyl silicone oil as a defoamer (Comparative Example 9) resulted in a significant decrease in the patch's adhesion, only preventing the drop of a size 20 or 23 ball. These experimental results further demonstrate the unexpected technical benefits of the silica + liquid paraffin defoamer of this solution, which not only effectively eliminates bubbles in the patch but also effectively maintains the patch's adhesion. The adhesion of non-aqueous transdermal patches is a key performance indicator, directly related to whether the drug can be released through the skin and into the systemic circulation within a predetermined time and at the expected rate. Good adhesion ensures good contact between the patch and the skin, ensuring that the patch adheres tightly to the skin surface throughout its use period and preventing displacement or dislodging due to external activities. Good adhesion not only helps maintain the therapeutic effect but also reduces the inconvenience and distress caused by frequent patch dropouts, thereby improving treatment compliance.

[0105] The above is only an embodiment of the present invention, and the common knowledge such as the specific technical solutions and / or characteristics in the solution are not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several variations and improvements can be made, which should also be regarded as the scope of protection of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the description can be used to interpret the content of the claims.

Claims

1. An application of a defoaming agent in a non-aqueous transdermal system patch, characterized in that: The defoaming agent is obtained by mixing silicon dioxide and liquid paraffin and then subjecting the mixture to heating treatment.

2. Use of a defoaming agent according to claim 1 in a non-aqueous transdermal system patch, characterized in that: The mass ratio of silicon dioxide to liquid paraffin is 1:7~10.

3. Use of a defoaming agent in a non-aqueous transdermal system patch according to claim 2, characterized in that: The temperature of the heating treatment is 110-140° C., and the duration is ≥1 hour; preferably, the heating treatment duration is 1-3 hours.

4. Use of a defoaming agent in a non-aqueous transdermal system patch according to claim 3, characterized in that: The non-aqueous transdermal system patch comprises 20-100 parts of a drug component, 350-550 parts of a colloid part, 363-442 parts of a plasticizer, 80-150 parts of a viscosity increasing agent, 2-5 parts of a transdermal enhancer, 3-6 parts of an antioxidant, 10-20 parts of a pH adjusting agent, and 3-6 parts of a defoaming agent based on the mass of silicon dioxide; Preferably, the non-aqueous transdermal system patch comprises 40-50 parts of a drug ingredient, 370-390 parts of a colloid part, 370-420 parts of a plasticizer, 125-140 parts of a viscosity increasing agent, 2-5 parts of a transdermal enhancer, 3-6 parts of an antioxidant, 10-20 parts of a pH adjusting agent, and 3-6 parts of a defoaming agent based on the mass of silicon dioxide.

5. Use of a defoaming agent in a non-aqueous transdermal system patch according to claim 4, characterized in that: The drug component includes a nonsteroidal anti-inflammatory drug; the colloid portion includes at least one of an ABA type block copolymer and polyisobutylene; Preferably, the pharmaceutical ingredients include at least one of loxoprofen and its sodium salt, ketoprofen, ibuprofen, aflotoprofen, flurbiprofen, diclofenac and its sodium salt, indomethacin and celecoxib; Preferably, the ABA type block copolymer includes at least one of styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene, styrene-isoprene-styrene, styrene-ethylene / butylene-styrene, and styrene-ethylene / propylene-styrene.

6. Use of a defoaming agent in a non-aqueous transdermal system patch according to claim 5, characterized in that: The plasticizer includes at least one of liquid paraffin, glycerin, and propylene glycol; The tackifier comprises at least one of hydrogenated rosin glycerol ester, terpene resin, and rosin; The transdermal enhancer includes at least one of menthol and L-menthol; The antioxidant includes at least one of butylated hydroxyanisole and butylated hydroxytoluene; The pH adjuster includes at least one of phosphoric acid, acetic acid and citric acid.

7. Use of a defoaming agent in a non-aqueous transdermal system patch according to claim 6, characterized in that: Its application method includes the following steps in sequence: S1: The colloid part, the tackifier, and part of the plasticizer are mixed at a temperature of 130-150°C and a rotation speed of 20-30 rpm until melted, and then kneaded for 1-2 hours; after cooling to 115-125°C, a mixture A is obtained; S2: mixing the drug component, the transdermal enhancer, the antioxidant, the pH adjuster and the remaining plasticizer, and homogenizing the mixture to obtain a mixture B; S3: adding the defoaming agent and the mixture B to the mixture A, and refining them at a temperature of 115-125° C. and a speed of 20-30 rpm for 1-1.5 hours to obtain a refined mixture C; S4: coating the mixture C on a carrier to obtain a non-aqueous transdermal system patch.

8. A defoaming agent for preparing hot melt adhesive patches, characterized in that: Its raw materials include silicon dioxide and liquid paraffin; Preferably, the defoaming agent is prepared by the following method: silicon dioxide and liquid paraffin are mixed in a ratio of 1:7-10, and then heated at 110-140° C. for ≥1 hour to obtain the defoaming agent.

9. A defoaming agent for preparing hot melt adhesive patches according to claim 8, characterized in that: The silicon dioxide is prepared by a precipitation method or a vapor phase method; Preferably, the silicon dioxide is prepared by a gas phase method; the particle size of the silicon dioxide is in the range of 5 to 40 nm and the specific surface area is in the range of 100 to 400 m 2 / g.

10. A method for preparing a non-aqueous transdermal system patch with reduced bubble content, characterized in that: The method includes the following steps: S1: The colloid part, the tackifier, and part of the plasticizer are mixed at a temperature of 130-150°C and a rotation speed of 20-30 rpm until melted, and then kneaded for 1-2 hours; after cooling to 115-125°C, a mixture A is obtained; S2: mixing the drug component, the transdermal enhancer, the antioxidant, the pH adjuster and the remaining plasticizer, and homogenizing the mixture to obtain a mixture B; S3: adding the defoaming agent and the mixture B to the mixture A, and refining them at a temperature of 115-125° C. and a speed of 20-30 rpm for 1-1.5 hours to obtain a refined mixture C; The defoaming agent is prepared by the following method: taking silicon dioxide and liquid paraffin in a mass ratio of 1:7-10, stirring at a temperature of 110°C-140°C and a speed of 20-30 rpm for 1-3 hours to obtain the defoaming agent; S4: coating the mixture C on a carrier to obtain a non-aqueous transdermal system patch; Preferably, the formula of the non-aqueous transdermal system patch is as follows, in parts by weight: 20-100 parts of the drug component, 350-550 parts of the colloid part, 363-442 parts of the plasticizer, 80-150 parts of the viscosity increasing agent, 2-5 parts of the transdermal enhancer, 3-6 parts of the antioxidant, 10-20 parts of the pH adjusting agent, and 3-6 parts of the defoaming agent calculated on the mass of the silicon dioxide; Preferably, the pharmaceutical ingredient comprises a nonsteroidal anti-inflammatory drug; the colloid portion comprises at least one of an ABA-type block copolymer and polyisobutylene; the plasticizer comprises at least one of liquid paraffin, glycerol, and propylene glycol; the tackifier comprises at least one of hydrogenated rosin glycerol ester, terpene resin, and rosin; the transdermal enhancer comprises at least one of menthol and L-menthol; the antioxidant comprises at least one of butylated hydroxyanisole and butylated hydroxytoluene; and the pH adjuster comprises at least one of phosphoric acid, acetic acid, and citric acid. Preferably, the amount of plasticizer used in step S1 is 100-200 parts.

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