Dibenzoyl peroxide gel and preparation method thereof
By improving the adsorbent composition and process conditions, a more stable and delicate benzoyl peroxide gel was prepared, solving the problems of poor photostability and heavy particle feel, and improving the product's performance.
Patent Information
- Application Number
- CN202410962901.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-07-18
- Publication Date
- 2026-01-20
AI Technical Summary
Existing benzoyl peroxide gel has poor photostability, is easily decomposed, and has a grainy feel when applied, affecting the user experience.
By employing new adsorbent compositions and process conditions, including the use of carbomer 980, polydimethylsiloxane and its derivatives, colloidal silica, and other materials, a more stable and delicate gel was prepared through high-pressure emulsification and pH adjustment.
It improves the photostability of benzoyl peroxide gel, reduces the grainy feel, and enhances the user experience.
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Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a preparation method of a benzoyl peroxide gel. BACKGROUND
[0002] The benzoyl peroxide gel is a commonly used external medicine, and is mainly used for treating acne (acne vulgaris), especially common acne. The main active ingredient of the benzoyl peroxide gel is benzoyl peroxide, which is a strong oxidant and has the characteristics of bactericidal and keratolytic.
[0003] In the patent CN110433135A, the type of the gel base carbomer is changed, carbomer 980 is used to replace carbomer 940, the problem of benzene residue is overcome, the side effects of the benzoyl peroxide gel are reduced, and in addition, the adsorbent in the patent uses an acrylate copolymer, the emulsification process is vacuum stirring, the vacuum degree is-0.06 MPa to-0.08 MPa, and the benzoyl peroxide gel produced by the production method meets the basic characteristic requirements such as viscosity and granularity, but the problem that the benzoyl peroxide is easily decomposed under light is not solved. The benzoyl peroxide gel prepared by the method and the commercially available benzoyl peroxide gel still have the problem of poor light stability, and need to be sealed and stored to avoid light and high temperature. In addition, some benzoyl peroxide gels may have a sand-like feeling when applied, which affects the use experience of patients.
[0004] Therefore, a new preparation process is urgently needed to improve the problems of poor light stability and heavy particle feeling of the benzoyl peroxide gel. SUMMARY
[0005] The application provides a preparation method of a benzoyl peroxide gel, which solves the problems of poor light stability and heavy particle feeling of the benzoyl peroxide gel.
[0006] The application provides a preparation method of a benzoyl peroxide gel, which comprises the following steps:
[0007] 1) Gel phase preparation: purified water, glycerol and carbomer 980 are sequentially added into the gel phase, and stirring is performed for standby;
[0008] 2) Active phase preparation: purified water, propylene glycol, poloxamer 182, disodium edetate and sodium docusate are sequentially added into a beaker, stirring is performed until the mixture is clear, then polydimethylsiloxane and its derivatives and colloidal silicon dioxide are slowly added, stirring is continuously performed until the mixture is uniformly dispersed, 5% benzoyl peroxide is added, and stirring is performed until the raw materials are uniformly dispersed;
[0009] 3) Active phase homogenization: high-pressure emulsification is started, and stirring is performed;
[0010] 4) Mixing of the gel phase and the active phase: the gel phase is poured into the active phase, and stirring is performed;
[0011] 5) Constant volume: add purified water to 100%;
[0012] 6) Adjust pH: add NaOH solution to adjust pH to 4.8-5.8.
[0013] Preferably, the amount of polydimethylsiloxane and its derivatives added during the preparation of the active phase is 2.8%-3.5%, preferably 3.2%.
[0014] Preferably, the pressure of high-pressure emulsification is set to 50-100 MPa, preferably 75 MPa.
[0015] Preferably, the polydimethylsiloxane and its derivatives can be polydimethylsiloxane, cyclomethicone, aminosilicone, polymethylphenylsiloxane, polyether polysiloxane copolymer.
[0016] Preferably, the amount of carbomer 980 added is preferably 0.60%-1.0%.
[0017] Preferably, the amount of poloxamer 182 and sodium docusate added is preferably 0.1%-0.3%, 0.04%-0.06%.
[0018] Preferably, the amount of colloidal silicon dioxide added is preferably 0.02%-0.05%.
[0019] Preferably, the amount of glycerin and propylene glycol added is preferably 3%-5%, 3%-5%.
[0020] Preferably, the amount of edetate disodium added is preferably 0.05%-0.15%.
[0021] The application also provides a dibenzoyl peroxide gel prepared by the above process.
[0022] In summary, the application has the following beneficial effects:
[0023] 1) Improve the light stability of the dibenzoyl peroxide gel: the dibenzoyl peroxide gel is an oxidizing agent, and the drug component may undergo chemical reaction under light, resulting in change of drug properties. Therefore, the dibenzoyl peroxide gel needs to be sealed and stored in the dark. The application changes the type of adsorbent and the process conditions to prepare a dibenzoyl peroxide gel with better light stability.
[0024] 2) The dibenzoyl peroxide gel has better fineness: some dibenzoyl peroxide gels may have a sandy feel when applied, affecting the user's experience. The dibenzoyl peroxide gel prepared by the preparation method provided by the application has finer particle size and better user experience.
[0025] The technical solutions in the embodiments of the present application will be clearly described below. Obviously, the described embodiments are only some, but not all, of the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by a person of ordinary skill in the art belong to the scope of protection of the present application. DETAILED DESCRIPTION
[0026] The terms "first", "second", and the like in the description and claims of the present application are used to distinguish similar objects, and are not used to describe a particular sequential or chronological order. It should be understood that the data thus used can be interchanged under appropriate circumstances, so that the embodiments of the present application can be implemented in an order other than that described herein, and the objects distinguished by "first", "second", and the like are generally of a kind and are not limited in number, for example, the first object can be one or more. In addition, "and / or" in the description and claims means at least one of the connected objects, and the character " / " generally represents an "or" relationship between the front and rear associated objects.
[0027] The present application is not limited to the above-mentioned specific embodiments, which are only illustrative and not limiting. A person of ordinary skill in the art can make many forms under the inspiration of the present application without departing from the scope of the present application and the scope of protection of the claims.
[0029] 1) Gel phase preparation:
[0030] In the gel phase, 30% purified water, 3%-5% glycerol and 0.6%-1.0% carbomer 980 were added in turn, the stirring speed was 300 rpm, and the gel phase was stirred until it was dissolved and mixed evenly, and was ready for use. The above-mentioned glycerol can be used in an amount of 3%, 4%, 5%, and preferably 4%; the carbomer 980 can be used in an amount of 0.6%, 0.8%, 1.0%, and preferably 0.8%.
[0031] 2) Active phase preparation:
[0032] 50% purified water, 3%-5% propylene glycol, 0.1%-0.3% poloxamer 182, 0.05%-0.15% disodium edetate and 0.04%-0.06% sodium docusate were added in turn to a beaker, the stirring speed was set to 300 rpm, and after the solution was clear, 2.8%-3.5% polydimethylsiloxane and its derivatives and 0.02%-0.05% colloidal silicon dioxide were slowly added, and stirring was continued until they were uniformly dispersed. 5% dibenzoyl peroxide was added, and the raw materials were stirred until they were uniformly dispersed.
[0033] The propylene glycol can be used in an amount of 3%, 4%, 5%, and preferably 4%;
[0034] The amount of poloxamer 182 used can be 0.1%, 0.2%, 0.3%, preferably 0.2%;
[0035] The amount of edetate disodium used can be 0.05%, 0.1%, 0.15%, preferably 0.1%;
[0036] The amount of sodium docusate used can be 0.04%, 0.05%, 0.06%, preferably 0.05%;
[0037] The amount of dimethicone and its derivatives used can be 2.8%, 3.2%, 3.5%, preferably 3.2%;
[0038] The dimethicone and its derivatives can be dimethicone, cyclomethicone, aminosilicone, polymethylphenylsiloxane, polyether polysiloxane copolymer;
[0039] The amount of colloidal silicon dioxide used can be 0.02%, 0.021%, 0.035%, 0.05%, preferably 0.021%.
[0040] 3) Active phase homogenization
[0041] Turn on high-pressure emulsification, pressure setting 50-100 MPa, speed 5000 rpm, mix for 8 min, then pause.
[0042] The pressure can be set to 50 MPa, 75 MPa, 100 MPa, preferably 75 MPa.
[0043] 4) Gel phase active phase mixing
[0044] Pour the gel phase into the active phase and stir, stirring speed: 300 rpm.
[0045] 5) Volume setting
[0046] Set the volume of the sample, add pure water to 100%.
[0047] 6) pH adjuster preparation
[0048] Prepare a 10% sodium hydroxide solution, add 10% NaOH solution to the sample, stir while adding, adjust the pH to 4.8-5.8, stirring speed: 300 rpm, stirring time: 30 min.
[0049] 7) Filling
[0050] The amount is 15g / branch.
[0051] The present application is described in detail by the following examples, but is not limited to the following various examples and comparative examples as long as the gist of the present application is followed.
[0052] Example 1
[0053] 1) Gel phase preparation:
[0054] In the gel phase, 30% purified water, 36 g of glycerol and 7.2 g of carbomer 980 were sequentially added, and stirring was performed at 300 rpm until the gel phase was dissolved and mixed uniformly, and then it was prepared for use.
[0055] 2) Active phase preparation:
[0056] In a beaker, 50% purified water, 36 g of propylene glycol, 1.8 g of poloxamer 182, 0.9 g of disodium edetate, and 0.45 g of sodium docusate were sequentially added, and stirring was performed at 300 rpm until the solution was clear. Then, 28.8 g of dimethicone and 0.189 g of colloidal silicon dioxide were slowly added, and stirring was continued until they were uniformly dispersed. Then, 45 g of dibenzoyl peroxide was added, and stirring was performed until the raw materials were uniformly dispersed.
[0057] 3) Homogenization of the active phase
[0058] The high-pressure emulsification was turned on, the pressure was set to 75 MPa, and the stirring speed was set to 5000 rpm. After 8 minutes of mixing, the stirring was stopped.
[0059] 4) Mixing of the gel phase and the active phase
[0060] The gel phase was poured into the active phase and stirred at 300 rpm.
[0061] 5) Volume adjustment
[0062] The sample was adjusted to the desired volume.
[0063] 6) Preparation of the pH adjuster
[0064] A 10% sodium hydroxide solution was prepared, and 10% NaOH solution was added to the sample while stirring. The pH was adjusted to 4.8-5.8, and stirring was performed at 300 rpm for 30 minutes. Then, the stirring was stopped, and the sample was taken as Sample 1.
[0065] 7) Filling
[0066] The filling amount was 15 g per unit.
[0067] Example 2
[0068] 1) Gel phase preparation:
[0069] Add 30% purified water, 36g glycerol and 7.2g carbomer 980 to the gel phase in sequence, stir at 300 rpm until the gel phase is dissolved and mixed, and set aside.
[0070] 2) Preparation of active phase:
[0071] Add 50% purified water, 36g propylene glycol, 1.8g poloxamer 182, 0.9g disodium edetate, and 0.45g sodium docusate to a beaker in sequence. Set the stirring speed to 300 rpm and stir until the solution is clear. Then slowly add 28.8g cyclomethylsiloxane and 0.189g colloidal silica and continue stirring until they are evenly dispersed. Add 45g benzoyl peroxide and stir until the raw materials are evenly dispersed.
[0072] 3) Homogenization of active phase
[0073] Start high-pressure emulsification, set the pressure to 75MPa and the rotation speed to 5000rpm, mix for 8 minutes, then pause.
[0074] 4) Mixing of gel phase and active phase
[0075] Pour the gel phase into the active phase and stir at 300 rpm.
[0076] 5) Set the volume
[0077] Adjust the volume of the sample.
[0078] 6) Preparation of pH adjuster
[0079] Prepare a 10% sodium hydroxide solution. Add the 10% NaOH solution to the sample while stirring. Adjust the pH to between 4.8 and 5.8. Stir at 300 rpm for 30 minutes. Stop stirring, take a sample, and record it as sample 2.
[0080] 7) Filling
[0081] 15g per tube.
[0082] Example 3
[0083] 1) Gel phase preparation:
[0084] Add 30% purified water, 36g glycerol and 7.2g carbomer 980 to the gel phase in sequence, stir at 300 rpm until the gel phase is dissolved and mixed, and set aside.
[0085] 2) Preparation of active phase:
[0086] Into the beaker, 50% purified water, 36g propylene glycol, 1.8g poloxamer 182, 0.9g disodium edetate and 0.45g sodium docusate were added in sequence, the stirring speed was set to 300rpm, after the solution was clear, 28.8g aminosilicone and 0.189g colloidal silicon dioxide were slowly added, and the stirring was continued until they were uniformly dispersed, 45g dibenzoyl peroxide was added, and the stirring was continued until the raw materials were uniformly dispersed.
[0087] 3) Active phase homogenization
[0088] High-pressure emulsification was started, the pressure was set to 75MPa, and the rotation speed was 5000rpm. After mixing for 8min, the stirring was paused.
[0089] 4) Gel phase-active phase mixing
[0090] The gel phase was poured into the active phase and stirred at a stirring speed of 300rpm.
[0091] 5) Volume setting
[0092] The sample was set to a constant volume.
[0093] 6) pH adjuster preparation
[0094] A 10% sodium hydroxide solution was prepared, and 10% NaOH solution was added to the sample while stirring, and the pH was adjusted to between 4.8-5.8, the stirring speed was 300rpm, the stirring time was 30min, the stirring was stopped, the sample was taken, and it was recorded as sample 3.
[0095] 7) Filling
[0096] The filling amount was 15g / branch.
[0097] Example 4
[0098] 1) Gel phase preparation:
[0099] Into the gel phase, 30% purified water, 36g glycerol and 7.2g carbomer 980 were added in sequence, and the stirring speed was 300rpm. After the gel phase was dissolved and mixed evenly, it was ready for use.
[0100] 2) Active phase preparation:
[0101] Into the beaker, 50% purified water, 36g propylene glycol, 1.8g poloxamer 182, 0.9g disodium edetate and 0.45g sodium docusate were added in sequence, the stirring speed was set to 300rpm, after the solution was clear, 28.8g polymethylphenylsiloxane and 0.189g colloidal silicon dioxide were slowly added, and the stirring was continued until they were uniformly dispersed, 45g dibenzoyl peroxide was added, and the stirring was continued until the raw materials were uniformly dispersed.
[0102] 3) Active phase homogenization
[0103] Start high pressure homogenization, pressure set at 75 MPa, speed at 5000 rpm, mix for 8 min, then pause.
[0104] 4) Gel phase active phase mixing
[0105] Pour the gel phase into the active phase and stir, stirring speed: 300 rpm.
[0106] 5) Volume setting
[0107] Set the volume of the sample.
[0108] 6) pH adjuster preparation
[0109] Prepare 10% sodium hydroxide solution, add 10% NaOH solution to the sample while stirring, adjust the pH to between 4.8-5.8, stirring speed: 300 rpm, stirring time: 30 min, stop, take sample, record as sample 4.
[0110] 7) Filling
[0111] Fill 15g per piece.
[0112] Example 5
[0113] 1) Gel phase preparation:
[0114] Add 30% purified water, 36g glycerol and 7.2g carbomer 980 to the gel phase in turn, stirring speed 300 rpm, stir until the gel phase is dissolved and mixed evenly, ready for use.
[0115] 2) Active phase preparation:
[0116] Add 50% purified water, 36g propylene glycol, 1.8g poloxamer 182, 0.9g disodium edetate and 0.45g sodium docusate to the beaker in turn, set the stirring speed to 300 rpm, stir until the solution is clear, then slowly add 28.8g polyether polysiloxane copolymer and 0.189g colloidal silicon dioxide, continue stirring until they are evenly dispersed, add 45g dibenzoyl peroxide, stir until the raw materials are evenly dispersed.
[0117] 3) Active phase homogenization
[0118] Start high pressure homogenization, pressure set at 75 MPa, speed at 5000 rpm, mix for 8 min, then pause.
[0119] 4) Gel phase active phase mixing
[0120] Pour the gel phase into the active phase and stir, stirring speed: 300 rpm.
[0121] 5) Volume setting
[0122] Bring sample to volume.
[0123] 6) pH adjuster preparation
[0124] Prepare 10% sodium hydroxide solution, add 10% NaOH solution to sample while stirring, adjust to pH between 4.8-5.8, stirring speed: 300 rpm, stirring time: 30 min, stop, take sample, record as sample 5.
[0125] 7) Filling
[0126] Fill 15 g per stick.
[0127] Example 6
[0128] 1) Gel phase preparation:
[0129] Add 30% purified water, 36 g glycerin and 7.2 g carbomer 980 to gel phase in order, stirring speed 300 rpm, stir until gel phase is dissolved and mixed evenly, ready for use.
[0130] 2) Active phase preparation:
[0131] Add 50% purified water, 36 g propylene glycol, 1.8 g poloxamer 182, 0.9 g disodium edetate and 0.45 g sodium docusate to beaker in order, set stirring speed to 300 rpm, after the solution is clear, slowly add 25.2 g dimethicone and 0.189 g colloidal silicon dioxide, continue stirring until they are evenly dispersed, add 45 g dibenzoyl peroxide, stir until the raw materials are evenly dispersed.
[0132] 3) Active phase homogenization
[0133] Turn on high-pressure emulsification, set pressure to 75 MPa, speed to 5000 rpm, mix for 8 min, then pause.
[0134] 4) Gel phase active phase mixing
[0135] Pour gel phase into active phase and stir, stirring speed: 300 rpm.
[0136] 5) Volume
[0137] Bring sample to volume.
[0138] 6) pH adjuster preparation
[0139] Prepare 10% sodium hydroxide solution, add 10% NaOH solution to sample while stirring, adjust to pH between 4.8-5.8, stirring speed: 300 rpm, stirring time: 30 min, stop, take sample, record as sample 6.
[0140] 7) Filling
[0141] Dosage 15 g / stick.
[0142] Example 7
[0143] 1) Gel phase preparation:
[0144] Add 30% purified water, 36 g of glycerin and 7.2 g of carbomer 980 in sequence into the gel phase, stirring speed 300 rpm, stirring until the gel phase is dissolved and mixed evenly, ready for use.
[0145] 2) Active phase preparation:
[0146] Add 50% purified water, 36 g of propylene glycol, 1.8 g of poloxamer 182, 0.9 g of disodium edetate and 0.45 g of sodium docusate into the beaker in sequence, set the stirring speed to 300 rpm, after the solution is clear, slowly add 31.5 g of dimethicone and 0.189 g of colloidal silicon dioxide, continue to stir until they are evenly dispersed, add 45 g of dibenzoyl peroxide, stir until the raw materials are evenly dispersed.
[0147] 3) Active phase homogenization
[0148] Turn on high-pressure emulsification, set the pressure to 75 MPa and the speed to 5000 rpm, mix for 8 min, then pause.
[0149] 4) Gel phase active phase mixing
[0150] Pour the gel phase into the active phase and stir, stirring speed: 300 rpm.
[0151] 5) Volume setting
[0152] Set the volume of the sample.
[0153] 6) pH adjuster preparation
[0154] Prepare a 10% sodium hydroxide solution, add 10% NaOH solution to the sample while stirring, adjust the pH to between 4.8-5.8, stirring speed: 300 rpm, stirring time: 30 min, stop, take sample, record as sample 5.
[0155] 7) Filling
[0156] Dosage 15 g / stick.
[0157] Example 8
[0158] 1) Gel phase preparation:
[0159] Add 30% purified water, 36g glycerol and 7.2g carbomer 980 to the gel phase in sequence, stir at 300 rpm until the gel phase is dissolved and mixed, and set aside.
[0160] 2) Preparation of active phase:
[0161] Add 50% purified water, 36g propylene glycol, 1.8g poloxamer 182, 0.9g disodium edetate, and 0.45g sodium docusate to a beaker in sequence. Set the stirring speed to 300 rpm and stir until the solution is clear. Then slowly add 28.8g polydimethylsiloxane and 0.189g colloidal silica and continue stirring until they are evenly dispersed. Add 45g benzoyl peroxide and stir until the raw materials are evenly dispersed.
[0162] 3) Homogenization of active phase
[0163] Start high-pressure emulsification, set the pressure to 50MPa and the rotation speed to 5000rpm, mix for 8 minutes, then pause.
[0164] 4) Mixing of gel phase and active phase
[0165] Pour the gel phase into the active phase and stir at 300 rpm.
[0166] 5) Set the volume
[0167] Adjust the volume of the sample.
[0168] 6) Preparation of pH adjuster
[0169] Prepare a 10% sodium hydroxide solution. Add the 10% NaOH solution to the sample while stirring. Adjust the pH to between 4.8 and 5.8. Stir at 300 rpm for 30 minutes. Stop stirring, take a sample, and record it as sample 8.
[0170] 7) Filling
[0171] 15g per tube.
[0172] Example 9
[0173] 1) Gel phase preparation:
[0174] Add 30% purified water, 36g glycerol and 7.2g carbomer 980 to the gel phase in sequence, stir at 300 rpm until the gel phase is dissolved and mixed, and set aside.
[0175] 2) Preparation of active phase:
[0176] Into the beaker, 50% purified water, 36g propylene glycol, 1.8g poloxamer 182, 0.9g disodium edetate and 0.45g sodium docusate were sequentially added, the stirring speed was set to 300rpm, after the solution was clear, 28.8g dimethicone and 0.189g colloidal silicon dioxide were slowly added, and stirring was continued until they were uniformly dispersed, 45g dibenzoyl peroxide was added, and stirring was continued until the raw materials were uniformly dispersed.
[0177] 3) Active phase homogenization
[0178] High-pressure emulsification was started, the pressure was set to 100MPa, and the rotation speed was 5000rpm. After mixing for 8min, the stirring was paused.
[0179] 4) Gel phase-active phase mixing
[0180] The gel phase was poured into the active phase and stirred at a stirring speed of 300rpm.
[0181] 5) Volume setting
[0182] The sample was set to a constant volume.
[0183] 6) pH adjuster preparation
[0184] A 10% sodium hydroxide solution was prepared, and 10% NaOH solution was added to the sample while stirring, and the pH was adjusted to between 4.8-5.8, the stirring speed was 300rpm, the stirring time was 30min, the stirring was stopped, the sample was taken, and it was recorded as sample 9.
[0185] 7) Filling
[0186] The filling amount was 15g / branch.
[0187] Comparative Example 1
[0188] 1) Gel phase preparation:
[0189] Into the gel phase, 30% purified water, 36g glycerol and 7.2g carbomer 980 were sequentially added, and the stirring speed was set to 300rpm. After the gel phase was dissolved and mixed evenly, it was ready for use.
[0190] 2) Active phase preparation:
[0191] Into the beaker, 50% purified water, 36g propylene glycol, 1.8g poloxamer 182, 0.9g disodium edetate and 0.45g sodium docusate were sequentially added, the stirring speed was set to 300rpm, after the solution was clear, 28.8g lauryl methacrylate / ethylene glycol dimethacrylate cross-linked copolymer and 0.189g colloidal silicon dioxide were slowly added, and stirring was continued until they were uniformly dispersed, 45g dibenzoyl peroxide was added, and stirring was continued until the raw materials were uniformly dispersed.
[0192] 3) Active phase homogenization
[0193] Start high pressure homogenization, pressure set at 75 MPa, speed at 5000 rpm, mix for 8 min, then pause.
[0194] 4) Gel phase active phase mixing
[0195] Pour the gel phase into the active phase and stir, stirring speed: 300 rpm.
[0196] 5) Volume setting
[0197] Set the volume of the sample.
[0198] 6) pH adjuster preparation
[0199] Prepare 10% sodium hydroxide solution, add 10% NaOH solution to the sample while stirring, adjust the pH to between 4.8-5.8, stirring speed: 300 rpm, stirring time: 30 min, stop, take sample, record as sample 10.
[0200] 7) Filling
[0201] Fill 15 g per piece.
[0202] Comparative Example 2
[0203] 1) Gel phase preparation:
[0204] Add 30% purified water, 36 g of glycerol and 7.2 g of carbomer 980 to the gel phase in turn, stir at 300 rpm until the gel phase is dissolved and mixed evenly, and reserve.
[0205] 2) Active phase preparation:
[0206] Add 50% purified water, 36 g of propylene glycol, 1.8 g of poloxamer 182, 0.9 g of disodium edetate and 0.45 g of sodium docusate to the beaker in turn, set the stirring speed to 300 rpm, stir until the solution is clear, then slowly add 22.5 g of dimethicone and 0.189 g of colloidal silicon dioxide, continue stirring until they are evenly dispersed, add 45 g of dibenzoyl peroxide, and stir until the raw materials are evenly dispersed.
[0207] 3) Active phase homogenization
[0208] Start high pressure homogenization, pressure set at 75 MPa, speed at 5000 rpm, mix for 8 min, then pause.
[0209] 4) Gel phase active phase mixing
[0210] Pour the gel phase into the active phase and stir, stirring speed: 300 rpm.
[0211] 5) Volume setting
[0212] Bring the sample to volume.
[0213] 6) pH adjuster preparation
[0214] Prepare 10% sodium hydroxide solution, add 10% NaOH solution to the sample, stirring while adding, adjust to pH between 4.8-5.8, stirring speed: 300 rpm, stirring time: 30 min, stop, take sample, record as sample 11.
[0215] 7) Filling
[0216] Fill the amount of 15g / branch.
[0217] Comparative Example 3
[0218] 1) Gel phase preparation:
[0219] Add 30% purified water, 36g glycerin and 7.2g carbomer 980 in sequence in the gel phase, stirring speed 300 rpm, stir until the gel phase is dissolved and mixed evenly, ready for use.
[0220] 2) Active phase preparation:
[0221] Add 50% purified water, 36g propylene glycol, 1.8g poloxamer 182, 0.9g disodium edetate and 0.45g sodium docusate in sequence to the beaker, set the stirring speed to 300 rpm, after the solution is clear, slowly add 34.2g dimethicone and 0.189g colloidal silicon dioxide, continue to stir until they are evenly dispersed, add 45g dibenzoyl peroxide, stir until the raw materials are evenly dispersed.
[0222] 3) Active phase homogenization
[0223] Turn on high pressure emulsification, set the pressure to 75MPa and the speed to 5000rpm, mix for 8min, then pause.
[0224] 4) Gel phase active phase mixing
[0225] Pour the gel phase into the active phase and stir, stirring speed: 300 rpm.
[0226] 5) Volume
[0227] Bring the sample to volume.
[0228] 6) pH adjuster preparation
[0229] Prepare 10% sodium hydroxide solution, add 10% NaOH solution to the sample, stirring while adding, adjust to pH between 4.8-5.8, stirring speed: 300 rpm, stirring time: 30 min, stop, take sample, record as sample 12.
[0230] 7) Filling
[0231] Dosage 15 g / branch.
[0232] Comparative Example 4
[0233] 1) Gel phase preparation:
[0234] Add 30% purified water, 36 g of glycerol and 7.2 g of carbomer 980 in the gel phase in sequence, stirring speed 300 rpm, stirring until the gel phase is dissolved and mixed evenly, ready for use.
[0235] 2) Active phase preparation:
[0236] Add 50% purified water, 36 g of propylene glycol, 1.8 g of poloxamer 182, 0.9 g of disodium edetate and 0.45 g of sodium docusate to the beaker in sequence, set the stirring speed to 300 rpm, after the solution is clear, slowly add 28.8 g of dimethicone and 0.189 g of colloidal silicon dioxide, continue to stir until they are evenly dispersed, add 45 g of dibenzoyl peroxide, stir until the raw materials are evenly dispersed.
[0237] 3) Active phase homogenization
[0238] Turn on high-pressure emulsification, set the pressure to 30 MPa and the speed to 5000 rpm, mix for 8 min, then pause.
[0239] 4) Gel phase active phase mixing
[0240] Pour the gel phase into the active phase and stir, stirring speed: 300 rpm.
[0241] 5) Volume setting
[0242] Set the volume of the sample.
[0243] 6) pH adjuster preparation
[0244] Prepare a 10% sodium hydroxide solution, add 10% NaOH solution to the sample while stirring, adjust the pH to between 4.8 and 5.8, stirring speed: 300 rpm, stirring time: 30 min, stop, take sample, record as sample 13.
[0245] 7) Filling
[0246] Dosage 15 g / branch.
[0247] Comparative Example 5
[0248] 1) Gel phase preparation:
[0249] Add 30% purified water, 36g glycerol and 7.2g carbomer 980 to the gel phase in sequence, stir at 300 rpm until the gel phase is dissolved and mixed, and set aside.
[0250] 2) Preparation of active phase:
[0251] Add 50% purified water, 36g propylene glycol, 1.8g poloxamer 182, 0.9g disodium edetate, and 0.45g sodium docusate to a beaker in sequence. Set the stirring speed to 300 rpm and stir until the solution is clear. Then slowly add 28.8g polydimethylsiloxane and 0.189g colloidal silica and continue stirring until they are evenly dispersed. Add 45g benzoyl peroxide and stir until the raw materials are evenly dispersed.
[0252] 3) Homogenization of active phase
[0253] Start high-pressure emulsification, set the pressure to 120MPa and the rotation speed to 5000rpm, mix for 8 minutes, then pause.
[0254] 4) Mixing of gel phase and active phase
[0255] Pour the gel phase into the active phase and stir at 300 rpm.
[0256] 5) Set the volume
[0257] Adjust the volume of the sample.
[0258] 6) Preparation of pH adjuster
[0259] Prepare a 10% sodium hydroxide solution. Add the 10% NaOH solution to the sample while stirring. Adjust the pH to between 4.8 and 5.8. Stir at 300 rpm for 30 minutes. Stop stirring, take a sample, and record it as sample 14.
[0260] 7) Filling
[0261] 15g per tube.
[0262] Comparative Example 6
[0263] 1) Gel phase preparation:
[0264] Add 30% purified water, 36g glycerol and 7.2g carbomer 980 to the gel phase in sequence, stir at 300 rpm until the gel phase is dissolved and mixed, and set aside.
[0265] 2) Preparation of active phase:
[0266] Into the beaker, 50% purified water, 36 g of propylene glycol, 1.8 g of poloxamer 182, 0.9 g of disodium edetate and 0.45 g of sodium docusate were sequentially added, the stirring speed was set to 300 rpm, after the solution was clear, 28.8 g of dimethicone and 0.189 g of colloidal silicon dioxide were slowly added, and stirring was continued until they were uniformly dispersed, and 45 g of dibenzoyl peroxide was added, and stirring was continued until the raw materials were uniformly dispersed.
[0267] 3) Active phase homogenization
[0268] Emulsification was started, the rotation speed was 5000 rpm, and after 8 min of mixing, it was paused.
[0269] 4) Mixing of gel phase and active phase
[0270] The gel phase was poured into the active phase and stirred at a stirring speed of 300 rpm.
[0271] 5) Volume setting
[0272] The sample was set to volume.
[0273] 6) Preparation of pH adjuster
[0274] A 10% sodium hydroxide solution was prepared, and 10% NaOH solution was added to the sample while stirring, and the pH was adjusted to between 4.8 and 5.8, the stirring speed was 300 rpm, the stirring time was 30 min, it was stopped, and the sample was taken as sample 15.
[0275] 7) Filling
[0276] The filling amount was 15 g per piece.
[0277] Table 1: Overview of the types and amounts of adsorbents used in Examples 1-9 and Comparisons 1-6, and whether high-pressure emulsification and high-pressure values were used
[0278]
[0279] The particle size of samples 1-15 was investigated according to the following method:
[0280] The raw material particle size test method was as follows: an appropriate amount of each of samples 1-15 was placed on a glass slide and spread into a thin layer, the thin layer area was equivalent to the area of the cover glass, a total of 3 pieces were coated, and the particle size and particle size distribution determination method (Chinese Pharmacopoeia 2015 edition General 0982 first method) was used for determination. The specific determination results are shown in Table 2.
[0281] Table 2: Measurement results of particle size in each sample
[0282] Sample <15 μm <20 μm <25 μm > 100 μm > 180 μm Sample 1 90.5％ 95.1％ 99.2％ 0.001％ None Sample 2 91.2％ 96.6％ 99.3％ 0.002％ None Sample 3 89.9％ 94.5％ 99.4％ 0.003％ None Sample 4 90.5％ 96.3％ 98.9％ 0.002％ None Sample 5 92.1％ 95.5％ 99.3％ 0.003％ None Sample 6 90.2％ 95.3％ 99.5％ 0.004％ None Sample 7 90.6％ 96.2％ 99.4％ 0.005％ None Sample 8 89.7％ 95.4％ 99.3％ 0.006％ None Sample 9 90.8％ 96.3％ 99.0％ 0.003％ None Sample 10 80.0％ 90.2％ 95.6％ 0.009％ None Sample 11 82.5％ 89.6％ 95.2％ 0.010％ None Sample 12 81.9％ 90.3％ 95.1％ 0.011％ None Sample 13 79.6％ 87.3％ 94.9％ 0.015％ None Sample 14 84.5％ 90.1％ 95.6％ 0.016％ None Sample 15 70.5％ 82.4％ 90.7％ 0.021％ None
[0283] (Standard quality of dibenzoyl peroxide gel: particle size control standard: no less than 95% of particles below 25 μm, no more than 1% of particles above 100 μm, no particles above 180 μm detected)
[0284] Comparing sample 1-5 and sample 10, it can be seen that the particle size <20 μm in sample 1-5 has reached more than 95%, and the particle size <25 μm can reach more than 99%, and the particle size in sample 1-5 is obviously finer than that in sample 10, thus it can be seen that under the same conditions, when using polydimethylsiloxane and its derivatives as adsorbent, the particles of dibenzoyl peroxide gel are finer, and the use is better.
[0285] Comparing sample 1 and sample 6, 7, 11, 12, it can be seen that the particle size <20 μm in sample 1, 6, 7 has reached more than 95%, and the particle size <25 μm can reach more than 99%, and the particle size in sample 1, 6, 7 is obviously finer than that in sample 11, 12, thus it can be seen that under the condition that other conditions are unchanged, when selecting polydimethylsiloxane and its derivatives as adsorbent and its content is 2.8-3.5%, the particles of dibenzoyl peroxide gel are finer, and the use is better.
[0286] Comparing sample 1 and sample 8, 9, 13, 14, it can be seen that the particle size <20 μm in sample 1, 8, 9 has reached more than 95%, and the particle size <25 μm can reach more than 99%, and the particle size in sample 1, 8, 9 is obviously finer than that in sample 13, 14, thus it can be seen that under the condition that other conditions are unchanged, when the pressure range of high pressure emulsification is 50-100 MPa in the selection of active phase homogenization, the particles of dibenzoyl peroxide gel are finer, and the use is better.
[0287] Comparing sample 1 and sample 15, it can be seen that the particle size <20 μm in sample 1 has reached more than 95%, and the particle size <25 μm can reach more than 99%, and the particle size in sample 1 is obviously finer than that in sample 15, thus it can be seen that under the condition that other conditions are unchanged, when selecting specific high pressure conditions in the active phase homogenization, the particles of dibenzoyl peroxide gel are finer, and the use is better.
[0288] The light stability of samples 1-15 was investigated, and the specific operation method is as follows:
[0289] 400 g of each of samples 1-15 was divided into two equal parts, one part was placed in a transparent conical flask and placed under a daylight simulation lamp, and the other part was placed in a brown conical flask and placed in a dim space. The light intensity of the daylight simulation lamp simulates the light intensity of a sunny day without clouds, about 1367 W / m 2The content of dibenzoyl peroxide in each sample was measured at 0 h, 2 h, 4 h, 6 h, and 8 h, respectively, by using the HPLC method. The measured content of dibenzoyl peroxide in each sample under different time, light and dark is shown in Table 3.
[0290] Table 3: The measured content of dibenzoyl peroxide in each sample under different time, light and dark (w / v*100%)
[0291]
[0292]
[0293] The content of dibenzoyl peroxide in the table is calculated as follows: weight of dibenzoyl peroxide / volume of water*100%
[0294] Comparing sample 1-5 and sample 10, it can be seen that the content of dibenzoyl peroxide in sample 1-5 is much higher than that in sample 10 under the condition of strong light without cloud on a sunny day after 2 h, 4 h, 6 h, and 8 h of light. Therefore, when the adsorbent is selected as polydimethylsiloxane and its derivatives, the light stability of the dibenzoyl peroxide gel is better under the condition that other conditions remain unchanged.
[0295] Comparing sample 1 and sample 6, 7, 11, and 12, it can be seen that the content of dibenzoyl peroxide in sample 1, 6, and 7 is much higher than that in sample 11 and 12 under the condition of strong light without cloud on a sunny day after 2 h, 4 h, 6 h, and 8 h of light. Therefore, when the adsorbent is selected as polydimethylsiloxane and its derivatives and the content thereof is 2.8-3.5%, the light stability of the dibenzoyl peroxide gel is better under the condition that other conditions remain unchanged.
[0296] Comparing sample 1 and sample 8, 9, 13, and 14, it can be seen that the content of dibenzoyl peroxide in sample 1, 8, and 9 is much higher than that in sample 13 and 14 under the condition of strong light without cloud on a sunny day after 2 h, 4 h, 6 h, and 8 h of light. Therefore, when the active phase is homogenized by selecting the pressure range of high-pressure emulsification as 50-100 MPa, the light stability of the dibenzoyl peroxide gel is better under the condition that other conditions remain unchanged.
[0297] Comparing sample 1 and sample 15, it can be seen that the content of dibenzoyl peroxide in sample 1 is much higher than that in sample 15 under the condition of strong light without cloud on a sunny day after 2 h, 4 h, 6 h, and 8 h of light. Therefore, when the active phase is homogenized by selecting high-pressure conditions, the light stability of the dibenzoyl peroxide gel is better under the condition that other conditions remain unchanged.
[0298] It is understood that the above embodiments are only exemplary for illustrating the principles of the present application, and the present application is not limited thereto. Various modifications and improvements can be made by those skilled in the art without departing from the spirit and scope of the present application, and these modifications and improvements are also considered as the protection scope of the present application.
Claims
1. A process for the preparation of a dibenzoyl peroxide gel, characterized in that, It comprises: 1) Gel phase preparation: purified water, glycerin and carbomer 980 are sequentially added in the gel phase, stirring for standby; 2) Active phase preparation: purified water, propylene glycol, poloxamer 182, disodium edetate and sodium docusate are sequentially added in the beaker, stirring until clear, then slowly adding polydimethylsiloxane and its derivatives and colloidal silicon dioxide, continue stirring until it is evenly dispersed, adding 5% dibenzoyl peroxide, stirring until the raw materials are evenly dispersed; 3) Active phase homogenization: open high pressure emulsification, stirring; 4) Gel phase active phase mixing: pour the gel phase into the active phase and stir; 5) Volumetric: add purified water to 100%; 6) Adjust pH: add NaOH solution to adjust the pH to 4.8-5.
8.
2. The process for the preparation of a gel of dibenzoyl peroxide according to claim 1, characterized in that, The amount of polydimethylsiloxane and its derivatives added in the preparation of the active phase is 2.8%-3.5%, preferably 3.2%.
3. The method of preparing a gel of dibenzoyl peroxide according to claim 1, characterized in that, The pressure of the high pressure emulsification is set to 50-100MPa, preferably 75Mpa.
4. The process for the preparation of a gel of dibenzoyl peroxide according to claim 1, characterized in that, The polydimethylsiloxane and its derivatives can be polydimethylsiloxane, cyclomethicone, aminosilicone, polymethylphenylsiloxane, polyether polysiloxane copolymer.
5. The process for the preparation of the gel of dibenzoyl peroxide according to claim 1, characterized in that, The amount of carbomer 980 added is preferably 0.60%-1.0%.
6. The process for the preparation of a gel of dibenzoyl peroxide according to claim 1, characterized in that, The amount of poloxamer 182 and sodium docusate added is preferably 0.1%-0.3%, 0.04%-0.06%.
7. The process for the preparation of a gel of dibenzoyl peroxide according to claim 1, characterized in that, The amount of colloidal silicon dioxide added is preferably 0.02%-0.05%.
8. The process for the preparation of the gel of dibenzoyl peroxide according to claim 1, characterized by the fact that, The amount of glycerin and propylene glycol added is preferably 3%-5%, 3%-5%.
9. The method of preparing a gel of dibenzoyl peroxide according to claim 1, characterized in that, The amount of disodium edetate added is preferably 0.05%-0.15%.
10. A dibenzoyl peroxide gel characterized in that, It is prepared according to the preparation method of the dibenzoyl peroxide gel of any one of claims 1-9.