Topical pharmaceutical composition

Abstract

An object of the present invention is to provide a formulation technique for improving the solubility and safety of Prednisolone Valerate Acetate in an external pharmaceutical composition containing Prednisolone Valerate Acetate.SOLUTION: An external pharmaceutical composition comprising Prednisolone Valerate Acetate and propylene glycol monocaprylate.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to an external pharmaceutical composition containing prednisolone valerate acetate, which has excellent solubility and stability. [Background technology]

[0002] Prednisolone valerate acetate (hereinafter sometimes referred to as "PVA") is a corticosteroid that has traditionally been used to treat eczema, dermatitis, rashes, insect bites, itching, heat rash, hives, etc.

[0003] Since PVA hydrolyzes during storage, pharmaceutical compositions containing PVA require formulations that improve the stability of PVA. For example, Patent Document 1 reports that in an external preparation containing PVA and a basic local anesthetic, PVA can be stabilized for a long period of time by adjusting the pH of the suspension to 3 to 7 when diluted 10 times with purified water.

[0004] Furthermore, PVA is poorly soluble in water and can be dissolved in oily bases such as liquid paraffin, but dissolving it in an oily base requires sufficient stirring time, making it difficult to quickly and easily formulate. Therefore, for pharmaceutical compositions containing PVA, there is a need for a technology that not only increases the stability of PVA but also increases the solubility of PVA to facilitate formulation. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2001-72603 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present disclosure is to provide a formulation technology that improves the solubility and stability of PVA in an external pharmaceutical composition containing PVA. [Means for solving the problem]

[0007] The present inventors have conducted extensive research to solve the above problems and have found that the inclusion of propylene glycol monocaprylate together with PVA in an external pharmaceutical composition significantly improves the solubility and stability of PVA. The present disclosure was completed based on this finding and further research.

[0008] That is, the present disclosure provides the inventions of the following aspects. Item 1. A pharmaceutical composition for external application containing prednisolone valerate acetate and propylene glycol monocaprylate. Item 2. The topical pharmaceutical composition according to Item 1, further comprising an oily base. Item 3. The topical pharmaceutical composition according to Item 2, wherein the oily base is at least one selected from the group consisting of hydrocarbon oils and higher alcohols. Item 4. The pharmaceutical composition for external application according to any one of Items 1 to 3, further comprising a nonionic surfactant and water. Item 5. The topical pharmaceutical composition according to Item 4, wherein the nonionic surfactant is at least one selected from the group consisting of polyoxyethylene hydrogenated castor oil and sorbitan fatty acid esters. Item 6. The pharmaceutical composition for external application according to any one of Items 1 to 5, further comprising lidocaine and / or a salt thereof. Item 7. The pharmaceutical composition for external application according to any one of Items 1 to 6, further comprising allantoin. Item 8. The pharmaceutical composition for external application according to any one of Items 1 to 7, further comprising a thickener. Item 9. The external pharmaceutical composition according to Item 8, wherein the thickener is a cellulose-based thickener. Item 10. The pharmaceutical composition for external application according to any one of Items 1 to 9, further comprising a polyhydric alcohol. Item 11. The external pharmaceutical composition according to Item 10, wherein the polyhydric alcohol is 1,3-butylene glycol. Item 12. The pharmaceutical composition for external application according to any one of Items 1 to 11, which is in the form of an oil-in-water emulsion. Item 13. The external pharmaceutical composition according to any one of Items 1 to 12, which is a cream or emulsion. [Effects of the Invention]

[0009] In the topical pharmaceutical composition of the present disclosure, the solubility of PVA is improved by propylene glycol monocaprylate, allowing PVA to dissolve in a short time during preparation. In addition, the decomposition of PVA over time is suppressed by propylene glycol monocaprylate, allowing the topical pharmaceutical composition of the present disclosure to have excellent storage stability. [Brief explanation of the drawings]

[0010] [Figure 1] 1 shows photographs showing typical appearances corresponding to evaluation criteria A, B, or D when evaluating the dissolution state of PVA after stirring for 5 minutes in Test Examples 1 to 3. DETAILED DESCRIPTION OF THE INVENTION

[0011] The topical pharmaceutical composition of the present disclosure is characterized by containing PVA and propylene glycol monocaprylate. The pharmaceutical composition of the present disclosure is described in detail below.

[0012] In the present disclosure, the expression "X to Y" regarding a numerical range refers to a numerical range of X or more and Y or less.

[0013] [PVA] The topical pharmaceutical composition of the present disclosure contains PVA (prednisolone valerate acetate). PVA is also known as prednisolone valerate acetate and is a compound known as a corticosteroid.

[0014] The content of PVA in the topical pharmaceutical composition of the present disclosure may be appropriately set depending on the dosage form, form, intended use, etc. of the topical pharmaceutical composition, and may be, for example, 0.01 to 5 wt %, preferably 0.01 to 3 wt %, more preferably 0.05 to 0.5 wt %, and even more preferably 0.1 to 0.3 wt %.

[0015] [Propylene glycol monocaprylate] The topical pharmaceutical composition of the present disclosure contains propylene glycol monocaprylate. By including PVA and propylene glycol monocaprylate in the topical pharmaceutical composition of the present disclosure, the solubility and stability of PVA are improved. Propylene glycol monocaprylate is a monoester of monocaprylic acid and propylene glycol.

[0016] In the topical pharmaceutical composition of the present disclosure, the ratio of PVA to propylene glycol monocaprylate is not particularly limited, but may be, for example, 0.1 to 200 parts by weight of propylene glycol monocaprylate per part by weight of PVA. From the viewpoint of more effectively improving the solubility and stability of PVA, the ratio of propylene glycol monocaprylate per part by weight of PVA is preferably 1 to 150 parts by weight, more preferably 5 to 100 parts by weight, even more preferably 10 to 50 parts by weight, particularly preferably 20 to 40 parts by weight, and especially preferably 30 to 35 parts by weight.

[0017] The content of propylene glycol monocaprylate in the topical pharmaceutical composition of the present disclosure may be set appropriately depending on the dosage form, shape, etc. of the topical pharmaceutical composition, and may be, for example, 0.1 to 98 wt %, preferably 0.5 to 15 wt %, more preferably 1 to 10 wt %, even more preferably 2 to 8 wt %, particularly preferably 3 to 7 wt %, and especially preferably 4 to 6 wt %.

[0018] [Lidocaine and / or its salts] The topical pharmaceutical composition of the present disclosure may contain lidocaine and / or a salt thereof as needed. In particular, when the topical pharmaceutical composition of the present disclosure is in an emulsified form and contains lidocaine and / or a salt thereof, the stability of PVA can be further improved. When the topical pharmaceutical composition of the present disclosure is in an emulsified form and contains lidocaine, lidocaine becomes a component of the oil phase.

[0019] Lidocaine and its salts are known compounds as local anesthetics. The type of lidocaine salt is not particularly limited, but examples thereof include lidocaine hydrochloride.

[0020] When lidocaine and / or a salt thereof is contained in the topical pharmaceutical composition of the present disclosure, the content is not particularly limited, but may be, for example, 0.01 to 7 wt %, preferably 0.1 to 5 wt %, more preferably 0.5 to 4 wt %, and even more preferably 1 to 4 wt %.

[0021] [Allantoin] The external pharmaceutical composition of the present disclosure may contain allantoin as needed.In particular, when the external pharmaceutical composition of the present disclosure is in an emulsified form and contains allantoin, it can further improve the stability of PVA.When the external pharmaceutical composition of the present disclosure is in an emulsified form and contains allantoin, allantoin may be contained as a component of either oil phase or water phase, but is preferably contained as a component of water phase.Allantoin is a compound known as a tissue repair component, anti-inflammatory agent, etc.

[0022] When allantoin is contained in the topical pharmaceutical composition of the present disclosure, the content thereof is not particularly limited, but may be, for example, 0.01 to 5 wt %, preferably 0.01 to 1 wt %, more preferably 0.05 to 0.5 wt %, and even more preferably 0.1 to 0.3 wt %.

[0023] [Thickener] The topical pharmaceutical composition of the present disclosure may contain a thickener as needed to impart viscosity, etc. In particular, when the topical pharmaceutical composition of the present disclosure is in an emulsion form, it is preferable that the aqueous phase contains a thickener.

[0024] The type of thickener is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include cellulose-based thickeners, polyvinyl-based thickeners, thickening polysaccharides, acrylic acid-based thickeners, etc. These thickeners may be used alone or in combination of two or more. Among these thickeners, cellulose-based thickeners are preferred.

[0025] Specific examples of cellulose-based thickeners include carboxymethyl cellulose and its salts (sodium salts), methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, etc. Among these cellulose-based thickeners, preferred are carboxymethyl cellulose and its salts, and more preferred are sodium carboxymethyl cellulose.

[0026] When a thickener is contained in the topical pharmaceutical composition of the present disclosure, the content thereof is not particularly limited, but may be, for example, 0.05 to 5% by weight, preferably 0.1 to 3% by weight, and more preferably 0.1 to 2% by weight.

[0027] [Polyhydric alcohol] The topical pharmaceutical composition of the present disclosure may contain a polyhydric alcohol as needed. In particular, when the topical pharmaceutical composition of the present disclosure is in an emulsion form, it is preferable that the aqueous phase contains a polyhydric alcohol.

[0028] The type of polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include ethylene glycol, 1,3-butylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, polypropylene glycol, glycerin, etc. These polyhydric alcohols may be used alone or in combination of two or more. Among these polyhydric alcohols, 1,3-butylene glycol is preferred.

[0029] When a polyhydric alcohol is contained in the topical pharmaceutical composition of the present disclosure, the content thereof is not particularly limited, but may be, for example, 0.1 to 20% by weight, preferably 0.5 to 15% by weight, even more preferably 1 to 12% by weight, and particularly preferably 5 to 10% by weight.

[0030] [Surfactants] The topical pharmaceutical composition of the present disclosure may contain a surfactant as needed. In particular, when the topical pharmaceutical composition of the present disclosure is in an emulsified form, it is preferable that a surfactant be contained to form the desired emulsified form.

[0031] The type of surfactant used in the present disclosure is not particularly limited, and may be any of a nonionic surfactant, anionic surfactant, cationic surfactant, and zwitterionic surfactant, with nonionic surfactants being preferred.

[0032] The type of nonionic surfactant is not particularly limited, but examples thereof include polyoxyethylene hydrogenated castor oil, sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene sorbitol fatty acid ester, sucrose fatty acid ester, etc. These nonionic surfactants may be used alone or in combination of two or more. Preferred examples of these nonionic surfactants include polyoxyethylene hydrogenated castor oil and sorbitan fatty acid ester.

[0033] The average number of moles of ethylene oxide (EO) added in polyoxyethylene hydrogenated castor oil is not particularly limited, but may be, for example, 5 to 100 moles, preferably 20 to 80 moles, and more preferably 40 to 80 moles. Among these, polyoxyethylene hydrogenated castor oil 60 is preferred.

[0034] The number of carbon atoms in the fatty acid constituting the sorbitan fatty acid ester is not particularly limited, but may be, for example, 10 to 22, preferably 14 to 22, and more preferably 16 to 20. Specific examples of sorbitan fatty acid esters include sorbitan monooleate, sorbitan monostearate, sorbitan sesquioleate, sorbitan sesquistearate, sorbitan coconut oil fatty acid, sorbitan monopalmitate, sorbitan tristearate, and sorbitan trioleate. Of these, sorbitan monostearate is preferred.

[0035] A suitable example of a nonionic surfactant to be incorporated into the topical pharmaceutical composition of the present disclosure is a combination of polyoxyethylene hydrogenated castor oil and a sorbitan fatty acid ester. When polyoxyethylene hydrogenated castor oil and a sorbitan fatty acid ester are used in combination as an oily base, the ratio thereof is not particularly limited, but examples thereof include 0.01 to 100 parts by weight, preferably 0.1 to 20 parts by weight, more preferably 0.5 to 10 parts by weight, and even more preferably 0.1 to 1 part by weight of the sorbitan fatty acid ester per part by weight of polyoxyethylene hydrogenated castor oil.

[0036] When a surfactant is contained in the topical pharmaceutical composition of the present disclosure, the content thereof may be appropriately determined depending on the dosage form and shape of the topical pharmaceutical composition, the type of surfactant, etc., and may be, for example, 0.5 to 20% by weight or 0.5 to 15% by weight. More specifically, when the topical pharmaceutical composition of the present disclosure is in an emulsion form, the total amount of surfactant is preferably 0.5 to 20% by weight, more preferably 1 to 15% by weight, and even more preferably 5 to 10% by weight.

[0037] [Oil-based base] When the topical pharmaceutical composition of the present disclosure is provided as an emulsion composition or an oily topical preparation (oily ointment, etc.), it contains an oily base.

[0038] The type of oily base is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include hydrocarbon oils, higher alcohols, vegetable oils, animal oils, cholesterol, fatty acid alkyl esters, fatty acids, silicone oils, etc. These oily bases may be used alone or in combination of two or more. Among these oily bases, hydrocarbon oils and higher alcohols are preferred.

[0039] The hydrocarbon oil is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include liquid paraffin, α-olefin oligomer, white petrolatum, etc. Among these hydrocarbon oils, preferred are liquid paraffin and white petrolatum.

[0040] In the present disclosure, a higher alcohol refers to a higher alcohol having 6 or more carbon atoms. Examples of higher alcohols include, preferably, higher alcohols having 6 to 34 carbon atoms, more preferably higher alcohols having 14 to 22 carbon atoms, and even more preferably higher alcohols having 16 to 18 carbon atoms. Specific examples of higher alcohols include linear higher alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, cetostearyl alcohol, cetanol, and oleyl alcohol; and branched higher alcohols such as ostearyl glycerin ether (batyl alcohol). Among these higher alcohols, linear higher alcohols are preferred, and cetostearyl alcohol (a mixture of cetanol and stearyl alcohol) is more preferred.

[0041] A suitable example of an oily base to be incorporated into the topical pharmaceutical composition of the present disclosure is a combination of a hydrocarbon oil and a higher alcohol. When a hydrocarbon oil and a higher alcohol are used in combination as an oily base, the ratio between them is not particularly limited, but for example, the higher alcohol may be present in an amount of 0.01 to 100 parts by weight, preferably 0.05 to 50 parts by weight, more preferably 0.1 to 10 parts by weight, and even more preferably 0.5 to 1 part by weight per part by weight of the hydrocarbon oil.

[0042] A more specific example of a suitable oil base to be incorporated into the topical pharmaceutical composition of the present disclosure is a combination of liquid paraffin, white petrolatum, and cetostearyl alcohol. When liquid paraffin, white petrolatum, and cetostearyl alcohol are used in combination as the oil base, the ratio thereof is not particularly limited, but examples include 0.01 to 100 parts by weight of white petrolatum and 0.01 to 200 parts by weight of cetostearyl alcohol per 1 part by weight of liquid paraffin; preferably 0.05 to 50 parts by weight of white petrolatum and 0.05 to 100 parts by weight of cetostearyl alcohol; more preferably 0.1 to 10 parts by weight of white petrolatum and 0.1 to 20 parts by weight of cetostearyl alcohol; and even more preferably 0.5 to 1.5 parts by weight of white petrolatum and 1 to 2 parts by weight of cetostearyl alcohol.

[0043] When an oily base is contained in the topical pharmaceutical composition of the present disclosure, the content thereof may be appropriately set depending on the dosage form, form, etc. of the topical pharmaceutical composition, and examples thereof include 1 to 98 wt %, 1 to 97 wt %, or 1 to 96 wt % of the total amount of oily base. More specifically, when the topical pharmaceutical composition of the present disclosure is in an emulsion form, the total amount of oily base is preferably 0.5 to 40 wt %, more preferably 5 to 25 wt %, and even more preferably 10 to 20 wt %.

[0044] [water] When the topical pharmaceutical composition of the present disclosure is provided as an emulsion composition or an aqueous topical preparation, water is contained as the aqueous base. When the topical pharmaceutical composition of the present disclosure contains water, the content of water may be appropriately determined depending on the dosage form, form, etc. of the topical pharmaceutical composition, and may be, for example, 1 to 98 wt %, 1 to 97 wt %, or 1 to 96 wt %. More specifically, when the topical pharmaceutical composition of the present disclosure is in an emulsion form, the content of the aqueous base is preferably 45 to 85 wt %, more preferably 50 to 70 wt %, and even more preferably 55 to 65 wt %.

[0045] [Other ingredients] In addition to the above-mentioned components, the topical pharmaceutical composition of the present disclosure may contain other commonly used additives as needed. Examples of such additives include pH adjusters, buffers, solubilizers, antiseptics, preservatives, antioxidants, stabilizers, flavorings, coloring agents, etc. When these additives are contained in the topical pharmaceutical composition of the present disclosure, the content thereof may be appropriately determined depending on the type of additive used, etc.

[0046] The topical pharmaceutical composition of the present disclosure may contain pharmacological ingredients in addition to the ingredients described above. Examples of such pharmacological ingredients include antihistamines, local anesthetics, anti-inflammatory agents, moisturizers, disinfectants, antibacterial agents, antipruritics, skin protectants, blood circulation promoters, vitamins, etc. These pharmacological ingredients may be used alone or in combination of two or more. Furthermore, when these pharmacological ingredients are contained in the topical pharmaceutical composition of the present disclosure, the content thereof may be appropriately determined depending on the type of pharmacological ingredient used, the expected effect, etc.

[0047] [Formulation and dosage form] The dosage form of the topical pharmaceutical composition of the present disclosure is not particularly limited as long as it is applicable transdermally, and may be any of liquid, semi-solid, solid, etc., but is preferably liquid or semi-solid.

[0048] The topical pharmaceutical composition of the present disclosure may be in either an emulsified or non-emulsified form, preferably an emulsified form. When the topical pharmaceutical composition of the present disclosure is in an emulsified form, it may be either an oil-in-water type or a water-in-oil type, preferably an oil-in-water type.

[0049] The formulation of the topical pharmaceutical composition of the present disclosure is not particularly limited as long as it is applicable transdermally, and examples thereof include creams, liquids (including lotions, sprays, aerosols, and emulsions), gels, foams, ointments, patches, etc. Among these, creams and emulsions are preferred, and oil-in-water emulsion creams and oil-in-water emulsions are more preferred.

[0050] [Application] The topical pharmaceutical composition of the present disclosure can exhibit anti-inflammatory, anti-allergic, immunosuppressive, and other effects due to the PVA it contains, and can therefore be used to treat psoriasis, urticaria inflexa, eczema / dermatitis, palmoplantar pustulosis, keratoderma tylodes palmaris progressiva, sweat rash, sweating rash, strophulus, lichen Vidal, insect bites, prurigo, and the like.

[0051] [Manufacturing method] The topical pharmaceutical composition of the present disclosure can be manufactured according to a known formulation method appropriate for the formulation form. For example, when the topical pharmaceutical composition of the present disclosure is in an emulsion form, it is prepared by preparing an aqueous phase raw material liquid containing a water-soluble component and an oil phase raw material liquid containing PVA, propylene glycol monocaprylate, and other oily components, and emulsifying the aqueous phase raw material liquid and the oil phase raw material liquid.

[0052] Furthermore, in the topical pharmaceutical composition of the present disclosure, the solubility of PVA is improved by propylene glycol monocaprylate, making it possible to shorten the dissolution time of PVA during production. Therefore, when producing the topical pharmaceutical composition of the present disclosure, it is desirable to dissolve PVA under conditions in which PVA and propylene glycol monocaprylate coexist. [Example]

[0053] The present disclosure will be explained in more detail below by showing examples, but it should not be construed as being limited to these examples.

[0054] Test Example 1: Evaluation of PVA solubility (1) The components shown in Table 1 were mixed and stirred at 80°C until the PVA was completely dissolved, to prepare a liquid oily topical preparation. After stirring for 5 minutes, the appearance of the oily topical preparation was observed, and the state of dissolution of the PVA was evaluated according to the following criteria. The time until the PVA was completely dissolved was also measured. <Evaluation criteria for PVA dissolution after 5 minutes of stirring> A: No undissolved (white) PVA is visible. The appearance is similar to (1) in Figure 1. B: Multiple pieces of undissolved (white) PVA are visible. The appearance is similar to (2) in Figure 1. C: A large amount of undissolved (white) PVA is observed. D: A significant amount of undissolved (white) PVA remains, resulting in a cloudy appearance similar to that of Figure 1 (3).

[0055] The results are shown in Table 1. When propylene glycol dicaprylate, diethyl sebacate, or isopropyl myristate was used, PVA could not be dissolved even after 5 minutes of stirring, and a stirring time of 15 minutes or more was required to completely dissolve the PVA (Comparative Examples 1 to 3). In contrast, when propylene glycol monocaprylate was used, PVA could be completely dissolved after 5 minutes of stirring (Example 1). In other words, these results demonstrate that propylene glycol monocaprylate improves the solubility of PVA and can shorten the time required to dissolve PVA during formulation.

[0056] [Table 1]

[0057] Test Example 2: Evaluation of PVA solubility (2) The components shown in Table 2 were mixed and stirred at 80°C until the PVA was completely dissolved, to prepare a liquid oily topical preparation. After stirring for 5 minutes, the appearance of the oily topical preparation was observed, and the state of dissolution of the PVA was evaluated according to the same criteria as in Test Example 1. The time until the PVA was completely dissolved was also measured.

[0058] The results are shown in Table 2. When PVA was mixed with liquid paraffin and stirred, a stirring time of 45 minutes was required to completely dissolve the PVA (Comparative Example 4). Furthermore, even when propylene glycol dicaprylate, diethyl sebacate, or isopropyl myristate was added to liquid paraffin, the PVA could not be dissolved by stirring for 5 minutes, and a stirring time of 15 minutes or more was required to completely dissolve the PVA (Comparative Examples 5 to 7). In contrast, when propylene glycol monocaprylate was added to liquid paraffin, the PVA could be completely dissolved by stirring for 5 minutes (Example 2). These results also confirmed that propylene glycol monocaprylate improves the solubility of PVA and can shorten the time required to dissolve PVA during formulation.

[0059] [Table 2]

[0060] Test Example 3: Evaluation of PVA solubility (3) The components shown in Table 3 were mixed and stirred at 80°C until the PVA was completely dissolved, to prepare a liquid oily topical preparation. After stirring for 5 minutes, the appearance of the oily topical preparation was observed, and the state of dissolution of the PVA was evaluated according to the same criteria as in Test Example 1. The time until the PVA was completely dissolved was also measured.

[0061] The results are shown in Table 3. Even when surfactants (polyoxyethylene hydrogenated castor oil 60 and sorbitan monostearate) were added to liquid paraffin, a stirring time of 43 minutes was required to completely dissolve the PVA (Comparative Example 8). Furthermore, even when propylene glycol dicaprylate, diethyl sebacate, or isopropyl myristate was added to liquid paraffin along with the surfactant, the PVA could not be dissolved by stirring for 5 minutes, and a stirring time of more than 13 minutes was required to completely dissolve the PVA (Comparative Examples 9 to 11). In contrast, when propylene glycol monocaprylate and a surfactant were added to liquid paraffin, the solubility of PVA was further improved, and the PVA was completely dissolved with just 3 minutes of stirring (Example 3). These results also confirmed that propylene glycol monocaprylate improves the solubility of PVA and can shorten the time required to dissolve PVA during formulation.

[0062] [Table 3]

[0063] Test Example 4: Evaluation of solubility and stability of PVA Creams (oil-in-water emulsion compositions) having the compositions shown in Table 4 were prepared. Specifically, first, the aqueous phase components shown in Table 4 were mixed at about 80°C to prepare an aqueous phase raw material solution. Separately, the oil phase components shown in Table 4 were mixed and stirred at a temperature of 80°C until the PVA was completely dissolved, to prepare an oil phase raw material solution. During the preparation of the oil phase raw material solution, the time until the PVA was completely dissolved was measured. Next, the oil phase raw material solution and the aqueous phase raw material solution were mixed and emulsified while heated to 80°C, to prepare a cream.

[0064] Each cream preparation obtained was filled into an aluminum laminated tube and stored at 40°C for 6 months. The PVA concentration in the cream preparation before and after storage was measured by high performance liquid chromatography, and the residual PVA rate was calculated according to the following formula.

number

[0065] The residual rate of the calculated PVA was evaluated for the stability of PVA according to the following criteria. <Evaluation Criteria for PVA Stability> A: The residual rate of PVA is 98% or more B: The residual rate of PVA is 95% or more and less than 98% C: The residual rate of PVA is 90% or more and less than 95% D: The residual rate of PVA is less than 90%

[0066] The results are shown in Table 4. The raw material liquid for the oil phase used in the preparation of the cream agent without propylene glycol monocaprylate (Comparative Examples 12 to 15) required a stirring time of 13 minutes or more to completely dissolve PVA during preparation, similar to the results of Test Example 3. Furthermore, in the cream agent without propylene glycol monocaprylate (Comparative Examples 12 to 15), the degree of decomposition of PVA was large after storage at 40°C for 6 months, and the stability of PVA was insufficient. In contrast, the raw material liquid for the oil phase used in the preparation of the cream agent containing propylene glycol monocaprylate (Example 4) was able to completely dissolve PVA with only 3 minutes of stirring during preparation. Furthermore, in the cream agent containing propylene glycol monocaprylate (Example 4), the decomposition of PVA could be suppressed after storage at 40°C for 6 months, and the stability of PVA was improved. From these results, it was confirmed that propylene glycol monocaprylate improves the solubility of PVA and also improves the storage stability of PVA.

[0067]

Table 4

[0068] Prescription example Creams (oil-in-water emulsion compositions) having the compositions shown in Table 5 were prepared in the same manner as in Test Example 4. The oil phase raw material solutions used to prepare the creams of Formulation Examples 1 to 5 allowed PVA to dissolve in a short time during preparation, shortening the production time compared to when propylene glycol monocaprylate was not included. Furthermore, the stability of PVA in the creams of Formulation Examples 1 to 5 was evaluated after storage at 40°C for 6 months in the same manner as in Test Example 4, and the storage stability of PVA was found to be excellent in all cases.

[0069] [Table 5]

Claims

1. A pharmaceutical composition for external application containing prednisolone valerate acetate and propylene glycol monocaprylate.

2. The topical pharmaceutical composition according to claim 1, further comprising an oily base.

3. The topical pharmaceutical composition according to claim 1 or 2, further comprising a nonionic surfactant and water.

4. 3. The external pharmaceutical composition according to claim 1, which is in the form of an oil-in-water emulsion.

5. 3. The external pharmaceutical composition according to claim 1, which is a cream or emulsion.

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