External gel composition

Abstract

Provided is a preparation that solves the problems of sagging, long-term stability, and texture in an externally applied gel containing a non-steroidal anti-inflammatory agent. 【Solution means】The following components (a) to (g): (a) Non-steroidal anti-inflammatory agent: 1% by mass or more (b) Isopropanol: 7.5 to 12.5% by mass (c) Pyrrolidone compound: 0.5 to 1% by mass (d) Gelator: 0.1 to 2% by mass (e) Nonionic surfactant: 0.1 to 2% by mass (f) Oil component: 1 to 10% by mass (g) Water containing, Component (e) is a combination of one or more nonionic surfactants selected from nonionic surfactants having an HLB of 10 or more and 20 or less and one or more nonionic surfactants selected from nonionic surfactants having an HLB of more than 2 and less than 10, and the total HLB value represented as the sum of the products of the HLB values and weight ratios of the constituent nonionic surfactants is 9.7 to 9.9. An externally applied gel composition that is a nonionic surfactant.

Description

Technical Field

[0001] The present invention relates to an external gel composition.

Background Art

[0002] Non-steroidal anti-inflammatory drugs have excellent anti-inflammatory and analgesic effects, and are formulated as external preparations that can avoid problems related to the first-pass effect, especially for superficial local lesions. Examples of dosage forms of such external preparations include patches, solutions, gels, ointments, creams, and aerosols. Among these, gels are a useful dosage form for large movable parts such as joints and are continuously used until symptoms such as arthritis, tenosynovitis, and muscle pain recover.

[0003] However, many commercially available external gels have problems related to their usability. One of them is the occurrence of stringiness during application. Stringiness means a dirty lump formed by the aggregation of the contained components. The occurrence of stringiness not only causes dirt but also raises concerns about a decrease in the therapeutic effect due to uneven application. Some gel compositions showing an effect of suppressing stringiness have been reported. For example, a gel composition characterized by containing hydroxypropyl cellulose, hydrophobized hydroxypropyl methylcellulose, and a hydrophilic surfactant (see Patent Document 1); an emulsified gel composition characterized by containing a nonionic water-soluble polymer, an anti-peeling agent, and a surfactant (see Patent Document 2); furthermore, a technology of a gel preparation characterized by containing a water-soluble polymer and talc has been reported (see Patent Document 3). These reports remain at the evaluation of sensory tests, such as being influenced by the experience values and conditions of the evaluators, making it difficult to obtain highly reliable data. It is necessary to fundamentally solve the occurrence of stringiness based on scientific grounds.

[0004] In addition, external gels also have problems related to the long-term storage stability of gels or emulsions, and the application feeling, such as being difficult to spread on the skin and being sticky.

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] Japanese Patent Publication No. 2021-11432 [Patent Document 2] Japanese Patent Publication No. 2011-173823 [Patent Document 3] International Publication No. 2019 / 167727 [Overview of the project] [Problems that the invention aims to solve]

[0006] The object of the present invention is to provide a formulation that solves the problems of preventing creasing, long-term stability, and application comfort in topical gel formulations containing nonsteroidal anti-inflammatory agents. [Means for solving the problem]

[0007] Therefore, the inventors first investigated how to evaluate factors such as creasing and ease of spreading using quantitative evaluation criteria rather than sensory evaluation, and clarified these criteria. Then, by investigating various ingredient combinations based on these criteria, they found that by adding a certain amount of pyrrolidone compound and isopropanol in addition to a nonsteroidal anti-inflammatory agent, a gelling agent, a nonionic surfactant having a specific HLB, an oily component, and water, it is possible to obtain an external gel composition that prevents creasing, has good viscosity and gel or emulsion stability, is easy to spread on the skin, and has a pleasant feel.

[0008] In other words, the present invention provides the following [1] to [7]. [1] The following ingredients (a) to (g): (a) Nonsteroidal anti-inflammatory drugs: 1% by mass or more (b) Isopropanol 7.5-12.5% ​​by mass (c) Pyrrolidone compound 0.5-1% by mass (d) Gelling agent 0.1-2% by mass (e) Nonionic surfactant 0.1-2% by mass (f) Oily component 1~10% by mass (g) water It contains, An external gel composition in which component (e) is a combination of one or more nonionic surfactants selected from nonionic surfactants with an HLB of 10 or more and one or more nonionic surfactants selected from nonionic surfactants with an HLB of 2 or more and less than 10, wherein the total HLB value expressed as the sum of the products of the HLB values ​​and weight ratios of the constituent nonionic surfactants is 9.7 to 9.9. [2] The topical gel composition according to [1], wherein component (e) is a combination of one or more polyoxyethylene polyoxypropylene alkyl ethers having an HLB of 10 or more and one or more selected from sorbitan fatty acid esters having an HLB of 2 or more and less than 10 and glycerin fatty acid esters having an HLB of 2 or more and less than 10. [3] The topical gel composition according to [1] or [2], wherein component (a) is one selected from diclofenac, loxoprofen, indomethacin, ketoprofen, acetylsalicylic acid and salts thereof. [4] An external gel composition according to any one of [1] to [3], wherein component (a) is diclofenac or a salt thereof. [5] An external gel composition according to any one of [1] to [4], wherein component (c) is N-methyl-2-pyrrolidone. [6] An external gel composition according to any one of [1] to [5], wherein component (d) is a carboxyvinyl polymer. [7] An external gel composition according to any one of [1] to [6], wherein the complex viscosity is 50 to 70 Pa·s. [Effects of the Invention]

[0009] The topical gel composition of the present invention suppresses the occurrence of creasing, has good viscosity and stability of the gel or emulsion system, is easy to spread on the skin and has a pleasant feel when applied, and also has good skin permeability of the active ingredient, a nonsteroidal anti-inflammatory agent. [Brief explanation of the drawing]

[0010] [Figure 1]Shows the phase changes in the kink generation evaluation tests of Example 1 and Comparative Examples 1 and 2. [Figure 2] Shows the change over time in the amount of diclofenac permeating through the skin in the skin permeability tests of Example 1 and Comparative Example 1. [Figure 3] Shows the change in apparent viscosity in the evaluation test of the feel in use of Example 1 and Comparative Examples 1 and 2. [Figure 4] Shows the change in the first normal stress difference in the evaluation test of the feel in use of Example 1 and Comparative Examples 1 and 2.

Mode for Carrying Out the Invention

[0011] The terms used in this specification are used in the meanings commonly used in the art, unless otherwise specified.

[0012] The present invention relates to an external gel composition containing a non-steroidal anti-inflammatory agent. One aspect thereof is the following components (a) to (g): (a) 1% by mass or more of a non-steroidal anti-inflammatory agent (b) 7.5 to 12.5% by mass of isopropanol (c) 0.5 to 1% by mass of a pyrrolidone compound (d) 0.1 to 2% by mass of a gelling agent (e) 0.1 to 2% by mass of a nonionic surfactant (f) 1 to 10% by mass of an oily component (g) water containing Component (e) is a combination of one or more nonionic surfactants selected from nonionic surfactants having an HLB of 10 or more and 20 or less and one or more nonionic surfactants selected from nonionic surfactants having an HLB of more than 2 and less than 10, and is a nonionic surfactant having a total HLB value represented as the sum of the products of the HLB values and weight ratios of the constituent nonionic surfactants of 9.7 to 9.9, and is an external gel composition.

[0013] Component (a) is a nonsteroidal anti-inflammatory agent and is the active ingredient of the topical gel composition of the present invention. The nonsteroidal anti-inflammatory agent is preferably one selected from, for example, diclofenac, loxoprofen, indomethacin, ketoprofen, acetylsalicylic acid, and salts thereof, and more preferably diclofenac or a salt thereof. Examples of such salts include alkali metal salts such as sodium and potassium; alkaline earth metal salts such as calcium and magnesium; ammonium salts; alkylamine salts such as dimethylamine, diethylamine, trimethylamine, and triethylamine; and alkanolamine salts such as monoethanolamine, diethanolamine, diisopropanolamine, triethanolamine, and triisopropanolamine. Furthermore, as a salt of diclofenac, "diclofenac sodium," which is listed in the Japanese Pharmacopoeia, is more preferable. From the viewpoint of exerting medicinal effects, the content of component (a) is preferably 1% by mass or more, and more preferably 1% by mass or more and 10% by mass or less, in the total composition.

[0014] Component (b) is isopropanol. In the topical gel composition of the present invention, isopropanol acts as a transdermal absorption enhancer and solvent. It has an excellent transdermal absorption-enhancing effect on diclofenac or its salts. Furthermore, compared to ethanol, isopropanol, being a secondary alcohol, has lower reactivity and is less likely to produce by-products with the active ingredient. Because it has a higher boiling point than ethanol, it can be stored relatively safely, and because it does not vaporize easily, its effect is more sustained. From the viewpoint of solubility of the active ingredient, transdermal absorption promoting effect, odor, and emulsification stability, the content of ingredient (b) is preferably 7.5 to 12.5% ​​by mass of the total composition.

[0015] Component (c) is a pyrrolidone compound. In the topical gel composition of the present invention, the pyrrolidone compound acts as a transdermal absorption enhancer and solvent. Examples of pyrrolidone compounds include N-methyl-2-pyrrolidone, pyrrolidone carboxylic acid, laurylpyrrolidone carboxylic acid, myristylpyrrolidone carboxylic acid, behenylpyrrolidone carboxylic acid, octyldodecylpyrrolidone carboxylic acid, and their salts. Of these, N-methyl-2-pyrrolidone, pyrrolidone carboxylic acid, and their salts are preferred because they have high hydrophilicity and a high effect in promoting transdermal absorption of the active ingredient, with N-methyl-2-pyrrolidone being more preferred. From the viewpoint of promoting transdermal absorption of the active ingredient, solubility, and emulsification stability, the content of ingredient (c) is preferably 0.1 to 5% by mass in the total composition.

[0016] Component (d) is a gelling agent. The gelling agent can be any water-soluble polymer, such as cellulose derivatives like methylcellulose, ethylcellulose, carmellose sodium, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and hydrophobized hydroxypropylmethylcellulose; natural polysaccharides like alginic acid or its salts, propylene glycol alginate, hyaluronic acid or its salts, carrageenan, xanthan gum, locust bean gum, and chitosan; polyamino acids like polyglutamic acid; polysilicic acids like magnesium aluminum silicate and light anhydrous silicic acid; synthetic polymers like carboxyvinyl polymer, sodium polyacrylate, partially neutralized polyacrylic acid, polyvinyl alcohol, and polyvinylpyrrolidone polymer; and polyphosphates like sodium metaphosphate. Of these, carboxyvinyl polymer is more preferred from the viewpoint of exhibiting high complex viscosity even with a small amount added in a water / isopropanol mixture. Furthermore, carboxyvinyl polymer is even more preferred from the viewpoint of contributing to the high emulsion stability in the present invention, as well as providing a pleasant application feel, due to its high thickening effect and excellent dispersion stability. Moreover, it is even more preferable to use a carboxyvinyl polymer with a pH of 3.0 to 3.5 and a complex viscosity of 30 to 50 mPa·s in a 0.2% aqueous solution, from the viewpoint of contributing to emulsion stability and providing a pleasant application feel. From the viewpoint of providing emulsification stability and a pleasant application feel, the content of component (d) is preferably 0.1 to 2% by mass, and more preferably 0.5 to 1% by mass, in the total composition.

[0017] Component (e) is a nonionic surfactant. Nonionic surfactants include one or more selected from hydrophilic nonionic surfactants and lipophilic nonionic surfactants. However, in the present invention, it is preferable to use a combination of one or more selected from nonionic surfactants with an HLB of 10 to 20 and one or more selected from nonionic surfactants with an HLB of 2 to less than 10 from the viewpoint of long-term emulsification stability. Furthermore, it is even more preferable from the viewpoint of long-term emulsification stability that the total HLB value of this nonionic surfactant, expressed as the sum of the products of the HLB values ​​and weight ratios of the constituent nonionic surfactants, is in the range of 9.7 to 9.9. As hydrophilic nonionic surfactants, nonionic surfactants with an HLB of 10 to 20 are preferred, and specifically include polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene polyoxypropylene alkyl ethers, polyoxyethylene hydrogenated castor oil, polyethylene glycol fatty acid esters, and the like. As lipophilic nonionic surfactants, nonionic surfactants with an HLB of 2 or more and less than 10 are preferred. Specifically, examples include propylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ethers, polyethylene glycol fatty acid esters, and the like.

[0018] In the present invention, it is preferable from the viewpoint of emulsification stability of the gel composition to use in combination one or more nonionic surfactants selected from those with an HLB of 10 or more and 20 or less and one or more nonionic surfactants selected from those with an HLB of 2 or more and less than 10. Here, as the nonionic surfactant with an HLB of 10 to 20, one or more selected from polyoxyethylene polyoxypropylene alkyl ethers with an HLB of 10 to 20 is preferred, and one or more selected from polyoxyethylene polyoxypropylene cetyl ethers with an HLB of 10 to 20 is more preferred. As the nonionic surfactant with an HLB of 2 or more and less than 10, one or more selected from glycerin fatty acid esters with an HLB of 2 or more and less than 10 and sorbitan fatty acid esters with an HLB of 2 or more and less than 10 are preferred. One or more selected from glycerin stearate esters with an HLB of 2 or more and less than 10 and sorbitan stearate esters are even more preferred.

[0019] Furthermore, from the viewpoint of improving the emulsification stability of the gel composition, it is preferable that the total HLB value of the nonionic surfactant mixture, which is expressed as the sum of the products of the HLB values ​​and weight ratios of the constituent nonionic surfactants, is in the range of 9.7 to 9.9. In this specification, HLB is a value calculated by the Griffin method. From the viewpoint of emulsification stability of the gel composition and suppression of skin irritation, the content of component (e) is preferably 0.1 to 2% by mass, and more preferably 0.55 to 1.2% by mass, in the total composition.

[0020] Component (f) is an oily component. Oily components are used to improve the solubility of the active ingredient. The oily component is not particularly limited as long as it is commonly used as an additive in pharmaceuticals. Examples include vegetable oils, alkyl fatty acid esters, polyhydric alcohol fatty acid esters, higher alcohols, hydrocarbons, and silicone oils. Of these, oily components that have excellent solubility for diclofenac, such as vegetable oils, alkyl fatty acid esters, and polyhydric alcohol esters, are preferred. Glyceryl triisooctanoate, with a specific gravity of 0.90 to 0.97, is even more preferred from the viewpoint of having a small specific gravity difference with the water / isopropanol mixture and good emulsification stability. From the viewpoint of the solubility of the active ingredient, the content of component (f) is preferably 1 to 10% by mass, and more preferably 3 to 7% by mass, in the total composition.

[0021] The component (g) is water. From the viewpoint of dissolving and hydrating the gelling agent, the water content is preferably 75% by mass or more, and more preferably 77-83% by mass, in the total composition.

[0022] In addition to the above-mentioned components, the topical gel composition of the present invention may contain a pH adjuster, a fragrance, an antioxidant, and a metal ion encapsulant. As pH adjusters, there are generally no particular restrictions as long as they are used as additives in pharmaceuticals. Examples include organic acids such as acetic acid, lactic acid, succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, maleic acid, adipic acid, and gluconic acid, their metal salts or ammonium salts; inorganic acids such as boric acid, hydrochloric acid, sulfuric acid, and phosphoric acid, their metal salts or ammonium salts; aqueous ammonia; alkanolamines such as monoethanolamine, diethanolamine, diisopropanolamine, trimethanolamine, triethanolamine, trometamol, and meglumine, or their inorganic salts; carbonates such as sodium carbonate, potassium carbonate, and calcium carbonate; bicarbonates such as sodium bicarbonate, potassium bicarbonate, and calcium bicarbonate; hydroxide salts such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide; phosphoric acid, monohydrogen phosphate heptahydrate, trisodium phosphate hydrate, disodium hydrogen phosphate dihydrate, dipotassium phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate hydrate; and methanesulfonic acid. These components may be used individually or in combination of two or more. Diisopropanolamine is particularly preferred as it does not contain salts that affect emulsification stability and is relatively low in reactivity. The amount of pH adjuster is preferably such that the pH of the gel composition is in the range of 6.2 to 7.0, and more preferably such that the pH is in the range of 6.5 to 6.9, from the viewpoints of making the pH slightly acidic, the same as the pH of the skin surface, the skin permeability of diclofenac, prevention of esterification reaction, and compatibility with the gelling agent. When diisopropanolamine is used as the pH adjuster, it is preferable to include 0.5 to 0.8% by mass in the total composition.

[0023] Examples of fragrances include orange, chamomile oil, cinnamon oil, clove oil, turpentine oil, spruce oil, cedarwood oil, bergamot oil, eucalyptus oil, lavender oil, lemon oil, rose oil, and Roman chamomile oil. Examples of antioxidants include sodium thiosulfate, sodium sulfite, ascorbic acid and its salts, tocopherol, dibutylhydroxytoluene, citric acid hydrate, anhydrous citric acid, dihydroxyanisole, benzotriazole, alpha-thioglycerin, and erythorbic acid. Sodium thiosulfate, which has excellent reducing power, is more preferred. It is preferable that the antioxidant be included in the total composition at a concentration of 0.05% by mass or more.

[0024] Examples of metal ion sequestering agents include propyl gallate, citric acid and its sodium salt, EDTA and its sodium salt, and phytic acid and its sodium salt. In the present invention, EDTA and its salts are preferred as metal ion sequestering agents, and disodium EDTA, whose aqueous solution has a weakly acidic pH, is more preferred. The content of the metal ion encapsulant is preferably 0.05% by mass or more in the total composition.

[0025] The complex viscosity of the external gel composition of the present invention should be such that it does not drip from the container and application area, and should be at least 15 Pa·s, more preferably 50 to 70 Pa·s. The complex viscosity can be measured, for example, using a rheometer.

[0026] An external gel composition according to an embodiment of the present invention can be obtained by weighing out each component and mixing them by stirring and phase inversion emulsification.

[0027] The topical gel composition of the present invention is used by topical administration to a local area (skin) where pain relief is required. The dosage of the topical gel composition of the present invention is appropriately set according to the site of administration, the severity of the symptoms to be treated, etc., but the local area of ​​administration is 1 cm². 2 It is desirable that the amount of diclofenac or its salt administered per dose is approximately 10 mg.

[0028] The topical gel composition of the present invention can be used for pain relief. Furthermore, because the present invention has excellent retention properties, it is suitable for use in areas with a high degree of mobility, such as shoulder pain associated with stiff shoulders, joint pain, and tennis elbow. The topical gel composition of the present invention is a gel composition that has excellent skin permeability and contains highly safe isopropanol, and can be used without worrying about the characteristic odor of isopropanol. The topical gel composition of the present invention can be applied evenly to localized areas where pain relief is required, without creasing or unevenness even after repeated careful application. It spreads easily and has low stickiness, making it comfortable to use. Although the topical gel composition of the present invention is white in appearance, it becomes colorless and transparent when spread, becoming completely inconspicuous. Therefore, the gel composition of the present invention is suitable for use on exposed areas. [Examples]

[0029] The present invention will be described in more detail below with reference to examples and comparative examples. These examples are not intended to limit the scope of the present invention.

[0030] The quantities of the ingredients listed in Tables 1 and 2 were measured out and prepared in accordance with Section 11-3, "Gel Preparations," of the Japanese Pharmacopoeia, to produce Examples 1-5 and Comparative Examples 1-4.

[0031] (Measurement of physical properties) The complex viscosity of the obtained examples and comparative examples was measured using a rheometer. [Measurement conditions for complex viscosity] Measuring instrument: HAAKE MARS 40 Plate: C35 2° / Ti Measurement temperature: 32.5℃ Strain: 0.1% Frequency: 1.0Hz

[0032] [Table 1]

[0033] [Table 2]

[0034] As shown in Tables 1 and 2, Examples 1-5 and Comparative Examples 1, 3-4 were gel compositions with sufficient viscosity. Comparative Example 2 did not exhibit desirable physical properties as an external gel composition.

[0035] (Stability of the emulsified state) The emulsification state of Examples 1-5 and Comparative Examples 1, 3-4 was examined using an optical microscope immediately after preparation. The emulsification state was also similarly examined after storage at 40°C and 75% RH for 3 months. The results are shown in Table 3. [Evaluation Criteria for Emulsification State] ◎: The micelle particles are small and uniform in size. ○: Some micelles have a slightly coarse particle size. △: Some micelles have a coarse particle size. ×: Large micelles are noticeable.

[0036] [Table 3]

[0037] Examples 1-5 demonstrated that the emulsified state remained stable over time. In Comparative Examples 1, 3-4, coarse micelles were observed after storage at 40°C and 75% RH for 3 months.

[0038] (Evaluation of wrinkle occurrence) The susceptibility of Example 1 to wrinkling was evaluated. Reference Examples 1 and 2, which are existing diclofenac gel formulations, were also evaluated in the same manner. The occurrence of warping was evaluated based on the change in phase (δ) measured under conditions simulating paint rubbing. Figure 1 shows the behavior of the phase (δ) change in Example 1 and Reference Examples 1 and 2. The point at which a decrease in phase was confirmed was defined as the onset point of warping, and the likelihood of warping occurring was evaluated based on the time taken from the start of measurement to the onset point of warping. Table 5 shows the measured warping onset times. [Conditions for evaluating the occurrence of wrinkles] Measuring instrument: HAAKE MARS 40 Plate: C35 2° / Ti Measurement temperature: 32.5℃ Distortion: 2900% Frequency: 2.8Hz Measurement time: 300 seconds

[0039] [Table 4]

[0040] Reference Example 1: Voltaren AC Gel Hydroxypropylcellulose, hydroxyethylcellulose, diisopropyl adipate, isopropanol, sodium pyrosulfite, lactic acid

[0041] Reference Example 2: Feitas Zα Dixus Gel Hydrophobized hydroxypropyl methylcellulose, hydroxypropylcellulose, propylene glycol, ethanol, dibutylhydroxytoluene, diethanolamine, polyoxyethylene behenyl ether, capsicum tincture, and 3 other ingredients.

[0042] [Table 5]

[0043] No wrinkling was observed in Example 1. Wrinkling was observed in Reference Examples 1 and 2. Unlike existing products, Example 1 can be used without worrying about wrinkling.

[0044] Skin permeability tests were conducted for Example 1 and Reference Example 1, and the amount of pharmacokinetics permeated the skin was compared with that of Reference Example 1. For the skin permeability tests, frozen skin collected from 8-week-old male HWY / Slc[SPF] hairless rats was used as the permeable membrane, and physiological saline was used as the receiver solution. Exposure to the test substance was divided into three doses, with approximately 10 mg of exposure in each dose. The quantitative determination of diclofenac sodium and its salts was performed according to the Japanese Pharmacopoeia General Test Methods "Liquid Chromatography". The results are shown in Table 6. Furthermore, the behavior of skin permeability from the start of the test to 28 hours is shown in Figure 2.

[0045] The equivalence of skin permeability was evaluated according to the guidelines for bioequivalence for prescription changes of topical skin application formulations (semi-solid formulations and transdermal patches). (Criteria for determining equivalence) ○: The ratio of the average skin permeability to Comparative Example 1 is within the range of 0.7 to 1.3. ×: The ratio of the average skin permeability to Comparative Example 1 is outside the range of 0.7 to 1.3.

[0046] [Table 6]

[0047] Example 1 demonstrated skin permeability equivalent to that of Reference Example 1. The same effects as those of Reference Example 1 were obtained.

[0048] The feel of using Example 1 was evaluated. Reference Examples 1 and 2, which are existing diclofenac gel formulations, were also evaluated in a similar manner. The feel of the product was evaluated under conditions simulating coating and rubbing. The evaluation was performed using the apparent viscosity and the rate of change (slope) of the first normal stress difference. The measured apparent viscosity is shown in Figure 3. The ease with which the gel composition could be spread on the skin was evaluated based on its apparent viscosity, and the tactile feel during application was evaluated based on the rate of change in the first normal stress difference. The measured first normal stress differences are shown in Figure 4. [Conditions for evaluating the feel of use] Measuring instrument: HAAKE MARS 40 Plate: C35 2° / Ti Measurement temperature: 32.5℃ Distortion: 2900% Frequency: 2.8Hz Measurement time: 120 seconds

[0049] [Table 7]

[0050] Compared to Reference Examples 1 and 2, Example 1 has a higher apparent viscosity, indicating that it spreads well on the skin and is an easy-to-apply gel composition. Furthermore, compared to Reference Example 2, Example 1 has a smaller slope of the first normal stress difference, indicating a less sticky and smoother feel.

Claims

1. The following ingredients (a) to (g): (a) Nonsteroidal anti-inflammatory drugs: 1% by mass or more (b) Isopropanol 7.5-12.5% ​​by mass (c) Pyrrolidone compound 0.5-1% by mass (d) Gelling agent 0.1-2% by mass (e) Nonionic surfactant 0.1-2% by mass (f) Oily component 1-10% by mass (g) water It contains, An external gel composition in which component (e) is a combination of one or more nonionic surfactants selected from nonionic surfactants with an HLB of 10 or more and one or more nonionic surfactants selected from nonionic surfactants with an HLB of 2 or more and less than 10, wherein the total HLB value expressed as the sum of the products of the HLB values ​​and weight ratios of the constituent nonionic surfactants is 9.7 to 9.

9.

2. The topical gel composition according to claim 1, wherein component (e) is a combination of one or more polyoxyethylene polyoxypropylene alkyl ethers having an HLB of 10 or more and one or more selected from sorbitan fatty acid esters having an HLB of 2 or more and less than 10 and glycerin fatty acid esters having an HLB of 2 or more and less than 10.

3. The topical gel composition according to claim 1 or 2, wherein component (a) is one selected from diclofenac, loxoprofen, indomethacin, ketoprofen, acetylsalicylic acid, and salts thereof.

4. The topical gel composition according to claim 1 or 2, wherein component (a) is diclofenac or a salt thereof.

5. The topical gel composition according to claim 1 or 2, wherein component (c) is N-methyl-2-pyrrolidone.

6. The topical gel composition according to claim 1 or 2, wherein component (d) is a carboxyvinyl polymer.

7. The topical gel composition according to claim 1 or 2, wherein the complex viscosity is 50 to 70 Pa·s.

Images