A hot-melt pressure-sensitive adhesive with high content of solid pharmaceutical ingredients and a preparation method thereof

Abstract

The application discloses a hot melt pressure-sensitive adhesive with high content of solid medicine components and a preparation method thereof, and belongs to the technical field of pressure-sensitive adhesive patches, in particular to a preparation method of the hot melt pressure-sensitive adhesive with high content of solid medicine components. In the application, the oil phase components such as plasticizers are used to pre-disperse the solid medicine components, and the pre-dispersed solid medicine components are preliminarily mixed with part of pressure-sensitive adhesive matrix glue; then, the rest of the pressure-sensitive adhesive matrix is secondarily mixed under certain conditions to form a drug-loaded pressure-sensitive adhesive; finally, the drug-loaded pressure-sensitive adhesive with high drug content is obtained by coating on a substrate backing. The application is characterized in that no other components (such as water, polar solvents and the like) are introduced, the medicine components are uniformly dispersed in the glue by the dispersion of the plasticizers and the secondary mixing, and the problems of agglomeration and hardening of the high-content medicine during mixing are effectively solved, and the adhesive force and the peeling strength are enhanced. The process preparation procedure is simple, and the drug loading capacity can reach 45%.

Description

Technical Field

[0001] This invention relates to the field of pressure-sensitive adhesive patch technology, and more specifically to a hot melt pressure-sensitive adhesive with a high content of solid drug components and its preparation method. Background Technology

[0002] Transdermal drug delivery systems (TDDS) refer to dosage forms in which drugs are absorbed through the skin into the systemic circulation, reaching effective blood drug concentrations to achieve disease treatment or prevention. As a core component of TDDS, pressure-sensitive adhesives not only ensure a tight fit between the patch and the skin but also act as a reservoir or carrier for the drug, directly determining the drug release behavior and the adhesive properties of the formulation. Hot-melt pressure-sensitive adhesives, due to their absence of organic solvents in their preparation process, offer advantages such as environmental friendliness, short production cycles, low energy consumption, and no solvent residue risks, making them a significant development direction for transdermal patch matrices.

[0003] With the diversification of clinical drug needs, especially for drugs requiring long-term administration or large doses, achieving high drug content and ensuring stable drug release while maintaining the adhesive properties of pressure-sensitive adhesives has become an industry trend. However, this leads to problems. As the content of drug components increases, especially for solid drugs (such as traditional Chinese medicine powders and drug granules), aggregation and hardening can occur in the pressure-sensitive adhesive matrix, damaging the colloidal structure, causing changes in the softening point and increased creep, leading to cold flow. Furthermore, uneven drug dispersion can result in aggregation, hardening, and carbonization, affecting efficacy. In addition, high drug loading and the addition of penetration enhancers can negatively impact the adhesion of pressure-sensitive adhesives (initial tack, holding power, peel strength). Traditional solutions often sacrifice drug loading by reducing drug content to maintain matrix stability, but this directly leads to increased patch area, higher costs, and greater inconvenience for users.

[0004] Patent CN118634208A proposes a method for pretreating pharmaceutical powder, but it introduces alcohol solvents outside the pressure-sensitive adhesive system. Furthermore, some alcohol solvents (such as ethanol) are highly volatile during the preparation of pressure-sensitive adhesives, affecting the performance of the pressure-sensitive adhesives.

[0005] Therefore, how to uniformly disperse high-concentration solid drugs in pressure-sensitive adhesives, while ensuring stable physical properties and excellent adhesion performance, and inhibiting problems such as drug aggregation and carbonization, is of great practical significance and application value for promoting the development of transdermal formulations. Summary of the Invention

[0006] This invention aims to provide a hot-melt pressure-sensitive adhesive with high solid drug content and its preparation method. By dispersing the drug in the oil phase and then mixing it with a colloidal matrix in a secondary process, the invention overcomes the problems of drug particle agglomeration caused by high drug content and changes in the adhesion of the pressure-sensitive adhesive.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] A hot melt pressure-sensitive adhesive with a high content of solid drug components, wherein, by mass percentage, its matrix comprises 10% to 40% thermoplastic elastomer, 20% to 60% plasticizer, 10% to 60% tackifying resin, and 0.25% to 10% excipients.

[0009] Preferably, the thermoplastic elastomer comprises one or more of SIS, ESIS, SBS, and ESBS.

[0010] Preferably, the plasticizer comprises one or more of naphthenic oil, liquid paraffin, DEP, DMP, and DBP.

[0011] Preferably, the tackifying resin includes one or more mixtures of petroleum resin and its hydrogenated petroleum resin, rosin resin, modified rosin, rosin glycerol ester, terpene resin and phenolic resin.

[0012] Preferably, the excipients include antioxidants, humectants, and penetration enhancers; wherein the humectants and penetration enhancers are added as needed.

[0013] Preferably, the antioxidant comprises one or more of the following: 168 (tris[2,4-di-tert-butylphenyl]phosphite), 1010 (pentaerythritol tetrakis[β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate]), and BHT (2,6-di-tert-butyl-p-cresol); The penetration enhancer includes one or more of the following: fatty acids (oleic acid, linoleic acid, etc.), fatty alcohols, isopropyl myristate, isopropyl palmitate, laurocapram, menthol (menthol, menthol, etc.), eugenol, and terpenes (carvone, thymol, limonene, etc.). The moisturizer includes one or more of glycerin, polyethylene glycol, sodium hyaluronate, and olive oil.

[0014] Another object of the present invention is to provide a method for preparing the above-mentioned hot melt pressure-sensitive adhesive with a high content of solid drug components, comprising: (1) Mix the drug components with the plasticizer until they are homogeneous to obtain the pretreated drug-containing components; (2) Add the prescribed amount of thermoplastic elastomer, antioxidant and the remaining amount of plasticizer to the flask, heat to 160°C and stir until completely melted, then cool to 140°C and add the prescribed amount of tackifying resin and stir until uniform to obtain pressure-sensitive adhesive matrix. (3) After a portion of the colloidal matrix and the drug-containing components are initially mixed, the temperature is kept below 110°C. The mixture is then added to the remaining colloidal matrix and stirred for 0.5 hours to complete the secondary mixing. The mixture is then coated and cut while hot to obtain the drug-loaded patch.

[0015] Preferably, the drug component is present in the hot melt pressure-sensitive adhesive at a mass ratio of 5% to 45%.

[0016] Preferably, the mass ratio of the plasticizer to the pharmaceutical ingredient is 1:3 to 2:1. More preferably, it is 1:1 to 2:1.

[0017] Preferably, the mass ratio of the drug-containing component to the colloidal matrix used in the initial mixing is 3:1 to 1:1.

[0018] As can be seen from the above technical solution, compared with the prior art, the present invention has the following technical effects: This invention can solve the problems of powder dispersion such as aggregation and hardening that occur when adding high-content powder through process adjustment, and the initial adhesion and peel strength are significantly improved. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0020] Figure 1 These are exterior photographs of Example 6 (left) and Comparative Example 1 (right).

[0021] Figure 2 The peeling curves are from three parallel experiments in Example 6.

[0022] Figure 3 The peeling curves are from three parallel tests in Comparative Example 1. Detailed Implementation

[0023] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] Example 1: 20% Chinese patent medicine powder; SIS 32%; Antioxidant content: 1680.25%; Antioxidant 10100.25% Naphthenic oil 22.5%; Tackifying resin hydrogenation C523%; Lauryl diazepine 2%; Preparation method: 20g of drug powder, 8g of naphthenic oil, and 2g of laurocapram were mixed and stirred until homogeneous to obtain a pretreated drug-containing component. The prescribed amount of SIS, antioxidant, and remaining naphthenic oil were added to a flask, heated to 160℃ and stirred until completely melted. The temperature was then lowered to 140℃, and the prescribed amount of tackifying resin was added and stirred until homogeneous to obtain a pressure-sensitive adhesive matrix. 30g of the adhesive matrix was mechanically kneaded and mixed with the drug-containing component, and the mixture was kept at 110℃. This mixture was then added to the remaining adhesive matrix and stirred for 0.5h. The mixture was then coated and cut while hot to obtain a drug-loaded patch.

[0025] Example 2: 35% of the extract is from traditional Chinese medicine. SIS 18%; Antioxidant content: 1680.25%; Antioxidant 10100.25% Liquid paraffin 11.6%; Rosin resin 24.5%; Zinc oxide 8.4%; Isopropyl palmitate 2%; Preparation method: 35g of herbal extract was mixed with 10g of liquid paraffin and 2g of isopropyl palmitate, and stirred until homogeneous to obtain a pretreated drug-containing component. In a flask, the prescribed amount of SIS, antioxidant, and the remaining liquid paraffin were added. The mixture was heated to 160℃ and stirred until completely melted. The temperature was then lowered to 140℃, and the prescribed amount of rosin resin and zinc oxide were added, stirring until homogeneous to obtain a pressure-sensitive adhesive matrix. 15g of the adhesive matrix was mechanically kneaded and mixed with the drug-containing component, and the mixture was kept at 110℃. This mixture was then added to the remaining adhesive matrix and stirred for 0.5h. The mixture was then coated and cut while hot to obtain a drug-loaded patch.

[0026] Example 3: Traditional Chinese medicine powder 10.4%; SIS 19.7%; Antioxidant content: 1680.25%; Antioxidant 10100.25% Liquid paraffin 39%; Hydrogenated rosin 23%; 5% white petrolatum; Menthol 2.4%; Preparation method: 10.4g of drug powder was mixed with 20g of liquid paraffin and 5g of white petrolatum, and stirred until homogeneous to obtain a pretreated drug-containing component. In a flask, the prescribed amount of SIS, antioxidant, and the remaining amount of liquid paraffin were added. The mixture was heated to 160℃ and stirred until completely melted. The temperature was then lowered to 140℃, and the prescribed amount of tackifying resin was added and stirred until homogeneous to obtain a pressure-sensitive adhesive matrix. 20g of the adhesive matrix was mechanically kneaded and mixed with the drug-containing component. The mixture was kept at 90℃, and the remaining adhesive matrix and menthol were added. Stirring continued for 0.5h. The mixture was then coated and cut while hot to obtain a drug-loaded patch.

[0027] Example 4: 15% Chinese patent medicine powder; SIS 17.5%; BHT 0.5%; Naphthenic oil 37.5%; Hydrogenated rosin 26.5%; Lauryl diazepine 2%; Eugenol 1%; Preparation method: 15g of drug powder, 12g of naphthenic oil, 2g of laurocapram, and 1g of eugenol were mixed and stirred until homogeneous to obtain a pretreated drug-containing component. The prescribed amount of SIS, antioxidant, and remaining naphthenic oil were added to a flask, heated to 160℃ and stirred until completely melted. The temperature was then lowered to 140℃, and the prescribed amount of tackifying resin was added and stirred until homogeneous to obtain a pressure-sensitive adhesive matrix. 30g of the adhesive matrix was mechanically kneaded and mixed with the drug-containing component, and the mixture was kept at 90℃. This mixture was then added to the remaining adhesive matrix and stirred for 0.5h. The mixture was then coated and cut while hot to obtain a drug-loaded patch.

[0028] Example 5: 25% Chinese patent medicine powder; SIS 18%; BHT 0.5%; Naphthenic oil 30.5%; Tackifying resin hydrogenated C524%; Lauryl diazepine 2%; Preparation method: 25g of drug powder, 23g of naphthenic oil, and 2g of laurocapram were mixed and stirred until homogeneous to obtain a pretreated drug-containing component. The prescribed amount of SIS, antioxidant, and the remaining amount of naphthenic oil were added to a flask, heated to 160℃ and stirred until completely melted. The temperature was then lowered to 140℃, and the prescribed amount of tackifying resin was added and stirred until homogeneous to obtain a pressure-sensitive adhesive matrix. 20g of the adhesive matrix was mechanically kneaded and mixed with the drug-containing component, and the mixture was kept at 110℃. This mixture was then added to the remaining adhesive matrix and stirred for 0.5h. The mixture was then coated and cut while hot to obtain a drug-loaded patch.

[0029] Example 6: 30% Chinese patent medicine powder; SIS 16.5%; Antioxidant content: 1680.25%; Antioxidant 10100.25% Liquid paraffin 23.5%; Rosin resin 27.5%; Linoleic acid 2%; Preparation method: Mix 30g of drug powder with 13g of liquid paraffin and 2g of linoleic acid, and stir until homogeneous to obtain a pretreated drug-containing component. Add the prescribed amount of SIS, antioxidant, and the remaining amount of liquid paraffin to a flask, heat to 160℃ and stir until completely melted, then cool to 140℃ and add the prescribed amount of tackifying resin, stirring until homogeneous to obtain a pressure-sensitive adhesive matrix. Take 23g of the adhesive matrix and mechanically knead and mix with the drug-containing component, maintain the temperature at 100℃, add to the remaining adhesive matrix and continue stirring for 0.5h. While hot, coat and cut to obtain the drug-loaded patch.

[0030] Comparative Example 1: 40% Chinese patent medicine powder; SIS 16.5%; Antioxidant content: 1680.25%; Antioxidant 10100.25% Liquid paraffin 13.5%; Rosin resin 27.5%; Linoleic acid 2%; Preparation method: Add the prescribed amount of SIS, antioxidant, and liquid paraffin to a flask, heat to 160℃ and stir until completely melted, then cool to 140℃, add the prescribed amount of tackifying resin and stir until homogeneous to obtain a pressure-sensitive adhesive matrix. Maintain the temperature at 100℃, add the prescribed amount of traditional Chinese medicine powder and continue stirring for 0.5 hours, then coat and cut while hot to obtain the drug-loaded patch.

[0031] Performance testing Appearance, adhesion, and peel strength were used as performance indicators for evaluating pressure-sensitive adhesive patches. All tests were conducted in accordance with the "General Rules of Part IV: 0952 Determination of Adhesion" in the 2025 edition of the Chinese Pharmacopoeia.

[0032] Initial tack test: Unless otherwise specified, the initial tack of plasters and patches shall be determined by the rolling ball ramp stop method. A suitable series of steel balls shall be rolled over the viscous surface of the test sample placed on an inclined plate. The initial tack shall be evaluated based on the largest steel ball that can adhere to the viscous surface of the test sample.

[0033] Adhesion test: The adhesive side of the test sample is attached to the surface of the test plate and placed vertically. A weight of a specified mass is suspended along the length of the test sample. The time it takes for the test sample to slide until it falls off or the distance it moves within a certain time is recorded.

[0034] Peel strength test: Fix the backing of the test sample to the test plate with double-sided tape. If necessary, use tape along the upper and lower edges of the test sample to ensure it is flat and adheres to the plate. Adhere the adhesive side of the test sample to a clean polyester film, then roll it back and forth three times with a 2000g weight to ensure no air bubbles are present at the adhesive joint. After pasting, allow the test sample to stand at room temperature for 20-40 minutes before testing. Fold the free end of the polyester film in half (180°), and clamp the free end of the film and the test plate onto the testing machine from the top and bottom, respectively. The peel surface should be aligned with the testing machine line. The testing machine continuously peels the sample at a descent speed of 300mm / min ± 10mm / min, and the peel curve is plotted by an automatic recorder.

[0035] The test results are shown in the table below:

[0036] The types and specifications of steel balls used in the initial tack test are shown in the table below:

[0037] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on its differences from other embodiments. Similar or identical parts between embodiments can be referred to interchangeably. For the apparatus disclosed in the embodiments, since it corresponds to the method disclosed in the embodiments, the description is relatively simple; relevant parts can be referred to the method section.

[0038] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A hot melt pressure-sensitive adhesive with a high content of solid drug components, characterized in that, By weight percentage, its matrix comprises 10% to 40% thermoplastic elastomer, 20% to 60% plasticizer, 10% to 60% tackifying resin, and 0.25% to 10% additives.

2. The hot melt pressure-sensitive adhesive with high solid drug component content according to claim 1, characterized in that, The thermoplastic elastomer includes one or more of SIS, ESIS, SBS, and ESBS.

3. The hot melt pressure-sensitive adhesive with high solid drug component content according to claim 1, characterized in that, The plasticizer includes one or more of naphthenic oil, liquid paraffin, DEP, DMP, and DBP.

4. The hot melt pressure-sensitive adhesive with high solid drug component content according to claim 1, characterized in that, The tackifying resin includes one or more mixtures of petroleum resin and its hydrogenated petroleum resin, rosin resin, modified rosin, rosin glycerol ester, terpene resin and phenolic resin.

5. The hot melt pressure-sensitive adhesive with high solid drug component content according to claim 1, characterized in that, The excipients include antioxidants, humectants, and penetration enhancers.

6. The hot melt pressure-sensitive adhesive with high solid drug component content according to claim 5, characterized in that, The antioxidants include one or more of the following: tris[2,4-di-tert-butylphenyl]phosphite, pentaerythritol tetrakis[β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate] and 2,6-di-tert-butyl-p-cresol; The penetration enhancer includes one or more of the following: fatty acids, fatty alcohols, isopropyl myristate, isopropyl palmitate, laurocapram, menthol, eugenol, and terpenes. The moisturizer includes one or more of glycerin, polyethylene glycol, sodium hyaluronate, and olive oil.

7. A method for preparing a hot-melt pressure-sensitive adhesive with a high content of solid drug components as described in any one of claims 1-6, characterized in that, (1) Mix the drug components with the plasticizer until they are homogeneous to obtain the pretreated drug-containing components; (2) Add the prescribed amount of thermoplastic elastomer, antioxidant and the remaining amount of plasticizer to the flask, heat to 160°C and stir until completely melted, then cool to 140°C and add the prescribed amount of tackifying resin and stir until uniform to obtain pressure-sensitive adhesive matrix. (3) After a portion of the colloidal matrix and the drug-containing components are initially mixed, the temperature is kept below 110°C. The mixture is then added to the remaining colloidal matrix and stirred for 0.5 hours to complete the secondary mixing. The mixture is then coated and cut while hot to obtain the drug-loaded patch.

8. The preparation method according to claim 7, characterized in that, The drug component is present in the hot melt pressure-sensitive adhesive at a mass ratio of 5% to 45%.

9. The preparation method according to claim 7, characterized in that, The mass ratio of the plasticizer to the drug component is 1:3 to 2:

1.

10. The preparation method according to claim 7, characterized in that, The mass ratio of the drug-containing component to the colloidal matrix used in the initial mixing is 3:1 to 1:1.

Images