Gel for treating acne and preparation method thereof

Abstract

The invention discloses gel for treating acne. The gel comprises a drug-loaded pellet, a matrix, a humectant, a bacteriostatic agent and a PH regulator, and the drug-loaded pellet comprises a blank pellet core, adapalene and an adhesive. The invention also provides a preparation method of the gel for treating acne, which comprises the following steps: 1) dissolving the adhesive in water, and then adding adapalene according to the prescription dosage to prepare a coating solution; coating, drying and sieving the blank pellet cores to prepare drug-loaded pellets 1-3 with different particle sizes; 2) dissolving the bacteriostatic agent and the humectant in water, adding the matrix, and uniformly stirring to obtain a mixed solution; and 3) respectively taking 1-3 parts of a certain amount of drug-loaded pellets, uniformly mixing, adding the mixed solution prepared in the step 2), stirring and homogenizing, adjusting the pH value to 5-6, adding water, and fully stirring to obtain the adapalene gel. The adapalene gel particles prepared by the invention are uniform in distribution, good in transdermal absorption effect and high in stability.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical technology, specifically relating to a gel for treating acne and its preparation method. Background Technology

[0002] Adapalene gel is a topical ointment used to treat acne (commonly known as "pimples"), belonging to the third-generation retinoid class of drugs. It helps reduce comedone formation by regulating skin cell growth and differentiation, and has anti-inflammatory properties that reduce acne inflammation. Adapalene gel is typically used to treat mild to moderate acne vulgaris, including acne on the face, chest, and back.

[0003] The main component of adapalene gel is adapalene, whose chemical name is 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid, and its molecular formula is C2. 28 H 28 O3, with a molecular weight of 412.53. It exerts its effect by binding to retinoic acid nuclear receptors, but unlike retinoic acid, adapalene does not bind to cytoplasmic receptors that bind to proteins, which makes it more selective and less irritating.

[0004] Adapalene has extremely low solubility in water and tends to form large particles during preparation, affecting drug efficacy and patient experience. Therefore, how to prepare adapalene gel with uniform particle size, good stability, and significant absorption has always been a research hotspot in the field of pharmaceutical formulation.

[0005] In addition, adapalene gel needs to be stored in a light-proof, sealed environment at a temperature below 25°C. Prolonged storage at excessively high temperatures can affect the chemical structure of adapalene, leading to drug degradation and consequently impacting its efficacy. Therefore, adapalene gel stored at high temperatures may experience reduced efficacy, or even become ineffective or deteriorate.

[0006] Therefore, the preparation of an adapalene gel with uniform particle size, significant absorption effect, and good stability remains an urgent problem to be solved. Summary of the Invention

[0007] This application provides an adapalene gel to solve the problems of uneven particle size distribution, poor absorption, and poor stability mentioned above.

[0008] This application provides an adapalene gel, comprising drug-loaded microspheres, a matrix, a humectant, an antibacterial agent, and a pH adjuster, wherein the drug-loaded microspheres include a blank microsphere core, adapalene, and a binder; the drug-loaded microspheres include drug-loaded microsphere 1, drug-loaded microsphere 2, and drug-loaded microsphere 3, and the particle size and amount of drug-loaded microsphere 1, drug-loaded microsphere 2, and drug-loaded microsphere 3 are different.

[0009] Preferably, the particle size D90 ranges of the drug-loaded microspheres 1, 2, and 3 are ≤0.6 mm, 0.7~1.1 mm, and 1.2~1.5 mm, respectively.

[0010] Preferably, the ratio of the amount of drug-loaded microspheres 1, 2, and 3 is (7-8):10:(13-15).

[0011] Preferably, the particle size D90 ranges of the drug-loaded microspheres 1, 2, and 3 are 0.4 mm, 0.8 mm, and 1.4 mm, respectively.

[0012] Preferably, the ratio of the amount of drug-loaded microspheres 1, 2, and 3 is 7.1:10:13.5.

[0013] Preferably, the drug-loaded microcapsules 2 include a blank core, adapalene, a binder, a plasticizer, and a pore-forming agent.

[0014] Preferably, the drug-loaded microcapsules 3 include a blank core, adapalene, a binder, a plasticizer, and a pore-forming agent.

[0015] Preferably, the adhesive is one or more of methylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, polyethylene glycol, and polyvinylpyrrolidone.

[0016] Preferably, the blank pellet core is selected from microcrystalline cellulose pellet cores.

[0017] The present invention also provides a method for preparing the above-mentioned adapalene gel, comprising:

[0018] 1) Dissolve the binder in water to prepare an adhesive aqueous solution. Then dissolve the prescribed amount of adapalene in the above adhesive aqueous solution to obtain a coating solution. Coat the blank pellet core, dry and sieve to obtain drug-loaded microparticles 1. Control the particle size D90 of drug-loaded microparticles 1 to be ≤0.6mm.

[0019] 2) Dissolve the binder in water to prepare an adhesive aqueous solution. Then dissolve the prescribed amount of adapalene in the above adhesive aqueous solution to obtain a coating solution. Coat the blank pellet core, dry and sieve to obtain drug-loaded microparticles 2. Control the particle size D90 of drug-loaded microparticles 2 to be 0.7-1.1 mm.

[0020] 3) Dissolve the binder in water to prepare an adhesive aqueous solution. Then dissolve the prescribed amount of adapalene in the above adhesive aqueous solution to obtain a coating solution. Coat the blank pellet core, dry and sieve to obtain drug-loaded microparticles 3. Control the particle size D90 of drug-loaded microparticles 3 to be 1.2-1.5 mm.

[0021] 4) Dissolve the antibacterial agent and humectant in water, add the matrix, stir well, and obtain a mixture.

[0022] 5) Take a certain amount of the above drug-loaded microspheres 1, 2, and 3, mix them evenly, and add them to the mixture prepared in step (4). After high-speed stirring and homogenization, add a pH adjuster to adjust the pH to 5-6, add water, and stir thoroughly to obtain adapalene gel.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0024] 1) Uniform particle distribution: This invention prepares drug-loaded microspheres with a certain particle size range by attaching the active ingredient adapalene to a blank pellet core, and mixes drug-loaded microspheres of different particle sizes in a certain proportion, which perfectly solves the problem in the prior art that the poor water solubility of adapalene makes it easy to form large particles during the preparation process, thus affecting the efficacy of the drug.

[0025] 2) High transdermal penetration rate and good therapeutic effect: By controlling the particle size and dosage ratio of the drug-loaded microspheres, this invention effectively controls the uniform distribution of active ingredients, thereby improving the transdermal penetration rate of adapalene gel and significantly enhancing its absorption effect.

[0026] 3) High stability: This invention attaches the active ingredients and binders together to the blank pellet core to form drug-loaded microparticles, which are then combined with other matrices and excipients to form a gel. This greatly increases the stability of adapalene gel, which maintains its physical state and the content of various substances stable even after being stored at high temperature for 60 days. Detailed Implementation

[0027] The technical solutions in the embodiments of this application are clearly described below. Obviously, the described embodiments are only some, not all, of the embodiments of this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application are within the scope of protection of this application.

[0028] The terms "first," "second," etc., used in the specification and claims of this application are used to distinguish similar objects and not to describe a specific order or sequence. It should be understood that such use of data can be interchanged where appropriate so that embodiments of this application can be implemented in orders other than those described herein, and the objects distinguished by "first," "second," etc., are generally of the same class and the number of objects is not limited; for example, a first object can be one or more. Furthermore, in the specification and claims, "and / or" indicates at least one of the connected objects, and the character " / " generally indicates that the preceding and following objects are in an "or" relationship.

[0029] This application is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of this application without departing from the spirit and scope of the claims, and all of these forms are within the protection scope of this application.

[0030] This application provides an adapalene gel, comprising drug-loaded microspheres, a matrix, a humectant, an antibacterial agent, and a pH adjuster, wherein the drug-loaded microspheres include a blank microsphere core, adapalene, and a binder; the drug-loaded microspheres include drug-loaded microsphere 1, drug-loaded microsphere 2, and drug-loaded microsphere 3, and the particle size and amount of drug-loaded microsphere 1, drug-loaded microsphere 2, and drug-loaded microsphere 3 are different.

[0031] The particle size D90 ranges of the drug-loaded microspheres 1, 2, and 3 are ≤0.6 mm, 0.7–1.1 mm, and 1.2–1.5 mm, respectively. The particle size D90 ranges of the drug-loaded microspheres 1, 2, and 3 can be 0.4 mm, 0.8 mm, 1.4 mm; 0.6 mm, 0.9 mm, 1.5 mm, respectively.

[0032] The dosage ratio of the drug-loaded microspheres 1, 2, and 3 is (7-8):10:(13-15). The dosage ratio of the drug-loaded microspheres 1, 2, and 3 can be 7.1:10:13.5; 8.0:10:13.5; 7.1:10:14; 7.1:10:15, etc.

[0033] Preferably, the drug-loaded microcapsules 2 include a blank core, adapalene, a binder, a plasticizer, and a pore-forming agent.

[0034] Preferably, the drug-loaded microcapsules 3 include a blank core, adapalene, a binder, a plasticizer, and a pore-forming agent.

[0035] The adhesive is one or more of methylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, polyethylene glycol, and polyvinylpyrrolidone.

[0036] The plasticizer may be one or more of citrate, diethyl phthalate, triacetin, polyethylene glycol, and distilled coconut oil.

[0037] The pore-forming agent may be one or more of fructose, sucrose, glucose, mannitol, galactose, lactose, polyethylene glycol, talc, hydroxypropyl methylcellulose, polyvinylpyrrolidone, methylcellulose, and hydroxypropyl cellulose.

[0038] The matrix can be carbomer.

[0039] The moisturizer may be propylene glycol or glycerin.

[0040] The antibacterial agent may be a paraben or potassium sorbate.

[0041] The pH adjuster can be sodium hydroxide.

[0042] The blank pellet core is selected from microcrystalline cellulose pellet cores.

[0043] The present invention also provides a method for preparing the above-mentioned adapalene gel, comprising:

[0044] 1) Dissolve the binder in purified water to prepare an aqueous binder solution. Then dissolve the prescribed amount of adapalene in the above aqueous binder solution to obtain a coating solution. Coat the blank pellet core, dry and sieve to obtain drug-loaded microparticles 1. Control the particle size D90 of drug-loaded microparticles 1 to be ≤0.6mm.

[0045] 2) Dissolve the binder in purified water to prepare an adhesive aqueous solution. Add the prescribed amount of plasticizer and pore-forming agent and mix well. Then dissolve the prescribed amount of adapalene in the above solution to obtain a coating solution. Coat the blank pellet core, dry and sieve to obtain drug-loaded microparticles 2. Control the particle size D90 of drug-loaded microparticles 2 to be 0.7-1.1 mm.

[0046] 3) Dissolve the binder in purified water to prepare an adhesive aqueous solution. Add the prescribed amount of plasticizer and pore-forming agent and mix well. Then dissolve the prescribed amount of adapalene in the above solution to obtain a coating solution. Coat the blank pellet core, dry and sieve to obtain drug-loaded microparticles 3. Control the particle size D90 of drug-loaded microparticles 3 to be 1.2-1.5 mm.

[0047] 4) Dissolve the antibacterial agent and humectant in water, add the matrix, stir well, and obtain a mixture.

[0048] 5) Take a certain amount of the above drug-loaded microspheres 1, 2, and 3, mix them evenly, and add them to the mixture prepared in step (4). After high-speed stirring and homogenization, add a pH adjuster to adjust the pH to 5-6, add water, and stir thoroughly to obtain adapalene gel.

[0049] The proportions are explained below with reference to specific embodiments.

[0050] Example 1

[0051] The prescription quantities are shown in Table 1.

[0052] Table 1. Formulas for each raw and auxiliary material in Example 1

[0053]

[0054] Preparation method:

[0055] 1) Dissolve the prescribed amount of methylcellulose in 80g of purified water to prepare a methylcellulose aqueous solution. Then dissolve the prescribed amount of adapalene in the above methylcellulose aqueous solution. Stir and sonicate for 10 minutes to obtain a coating solution. Coat the blank pellet core with a fluidized bed, dry and sieve to obtain drug-loaded microparticles 1. Control the particle size D90 of drug-loaded microparticles 1 to be 0.4mm.

[0056] 2) Dissolve the prescribed amount of methylcellulose in 80g of purified water, add the prescribed amounts of citrate and talc, mix well, and finally add the prescribed amount of adapalene to prepare a protective coating solution. Take the prescribed amount of drug-loaded microspheres, coat them with a fluidized bed coating, dry and sieve to obtain drug-loaded microspheres 2 with a protective layer, and control the particle size D90 of drug-loaded microspheres 2 to be 0.8mm.

[0057] 3) Dissolve the prescribed amount of methylcellulose in 80g of water, add the prescribed amounts of citrate and talc, mix well, and finally add the prescribed amount of adapalene to prepare a protective coating solution. Take the prescribed amount of drug-loaded microspheres, coat them with a fluidized bed coating, dry and sieve to obtain drug-loaded microspheres 3, and control the particle size D90 of drug-loaded microspheres 3 to be 1.4mm.

[0058] 4) Dissolve the prescribed amount of potassium sorbate and propylene glycol in 200g of purified water, add the prescribed amount of carbomer 980, stir well, and obtain a mixture.

[0059] 5) Take the above drug-loaded microspheres 1, 2 and 3 and mix them evenly. Then add them to the mixture prepared in step (4). After high-speed stirring and homogenization, add sodium hydroxide as a pH adjuster to adjust the pH to 5.5. Add purified water to a quantity of 1000g. After stirring thoroughly, adapalene gel 1 is obtained.

[0060] Examples 2-3

[0061] The difference between Examples 2 and 3 and Example 1 lies in the different particle sizes (D90) of drug-loaded microspheres 1, 2, and 3. In Example 2, the particle size (D90) of drug-loaded microsphere 1 is 0.6 mm, that of drug-loaded microsphere 2 is 0.9 mm, and that of drug-loaded microsphere 3 is 1.5 mm. In Example 3, the particle size (D90) of drug-loaded microsphere 1 is 0.6 mm, that of drug-loaded microsphere 2 is 1.1 mm, and that of drug-loaded microsphere 3 is 1.5 mm. Other formulation amounts and preparation methods are consistent with Example 1, yielding adapalene gels 2 and 3 respectively.

[0062] Examples 4-6

[0063] The difference between Examples 4-6 and Example 1 lies in the different ratios of the amounts of drug-loaded microspheres 1, 2, and 3. The specific amounts of drug-loaded microspheres 1, 2, and 3 in Examples 4-6 are shown in Table 2. Other amounts and preparation methods are the same as in Example 1, resulting in the preparation of adapalene gels 4-6.

[0064] Table 2 shows the specific dosages of drug-loaded microcapsules 1, 2, and 3 in Examples 4-6.

[0065]

[0066]

[0067] Comparative Examples 1-6

[0068] The only difference between Comparative Examples 1-6 and Example 1 is the particle size D90 of drug-loaded microspheres 1, 2, and 3. In Comparative Example 1, the particle size D90 of drug-loaded microsphere 1 is 0.8 mm, drug-loaded microsphere 2 is 0.8 mm, and drug-loaded microsphere 3 is 1.4 mm; in Comparative Example 2, the particle size D90 of drug-loaded microsphere 1 is 0.4 mm, drug-loaded microsphere 2 is 1.3 mm, and drug-loaded microsphere 3 is 1.4 mm; in Comparative Example 3, the particle size D90 of drug-loaded microsphere 1 is 0.4 mm, drug-loaded microsphere 2 is 0.8 mm, and drug-loaded microsphere 3 is 1.8 mm; in Comparative Example 3, the particle size D90 of drug-loaded microsphere 1 is 0.4 mm, drug-loaded microsphere 2 is 0.8 mm, and drug-loaded microsphere 3 is 1.8 mm; in Comparative Example 3, the particle size D90 of drug-loaded microsphere 1 is 0.4 mm, and drug-loaded microsphere 2 is 0.8 mm, and drug-loaded microsphere 3 is 1.3 mm, and drug-loaded microsphere 3 is 1.4 mm. The particle size D90 of the drug-loaded microspheres was 0.8 mm, and the particle size D90 of the drug-loaded microspheres 3 was 1.8 mm; in Comparative Example 4, the particle size D90 of the drug-loaded microspheres 1 was 0.8 mm, the particle size D90 of the drug-loaded microspheres 2 was 1.3 mm, and the particle size D90 of the drug-loaded microspheres 3 was 1.4 mm; in Comparative Example 5, the particle size D90 of the drug-loaded microspheres 1 was 0.4 mm, the particle size D90 of the drug-loaded microspheres 2 was 1.3 mm, and the particle size D90 of the drug-loaded microspheres 3 was 1.8 mm; in Comparative Example 6, the particle size D90 of the drug-loaded microspheres 1 was 0.8 mm, the particle size D90 of the drug-loaded microspheres 2 was 1.3 mm, and the particle size D90 of the drug-loaded microspheres 3 was 1.8 mm. Other formulation amounts and preparation methods were consistent with Example 1, and adapalene gels 7–12 were prepared respectively.

[0069] Comparative Examples 7-10

[0070] The difference between Comparative Examples 7-10 and Example 1 lies in the different ratios of drug-loaded microspheres 1, 2, and 3. The specific formulation amounts of drug-loaded microspheres 1, 2, and 3 in Comparative Examples 7-10 are shown in Table 2. Other formulation amounts and preparation methods are the same as in Example 1, yielding 13-16 liters of adapalene gel respectively.

[0071] Table 3 shows the specific dosages of drug-loaded microcapsules 1, 2, and 3 in Comparative Examples 7–10.

[0072]

[0073]

[0074]

[0075] For a detailed statistical analysis of the variables set in each embodiment, please refer to Table 4.

[0076] Table 4. Statistics of variables set in the comparative examples of each embodiment.

[0077]

[0078] In vitro transdermal experiments were conducted on the adapalene gels 1-16 prepared in Examples 1-6 and Comparative Examples 1-10.

[0079] The in vitro transdermal assay method is as follows: A 1.5cm diameter... 2 An in vitro transdermal assay was conducted using a 12ml Franz diffusion cell as the receiving chamber, 1-month-old Bama miniature pig skin as the skin barrier, and physiological saline as the receiving solution, with the temperature set at 32℃. Sampling time points were set at 0, 2, 4, 8, 12, and 24 hours. After the assay, residual solvent on the skin surface was blotted dry with absorbent paper. The skin that was not in direct contact with the gel was cut off with scissors, leaving only a piece of skin equal to the area of ​​the cell opening (i.e., 1.77cm2). The treated skin was weighed, then cut into strips and placed in a grinding cup, where it was frozen in liquid nitrogen for at least 1 hour.

[0080] Transfer the grinding balls directly to a 50ml EP tube. Wipe the grinding cup with a degreased cotton swab. Transfer the powder to the EP tube. Prepare 5ml of diluent 1 and wash the grinding cup in small amounts several times. Wipe the inside of the grinding cup with a degreased cotton swab. Prepare 20ml of diluent 2 and wash the grinding cup. Wipe the inside of the grinding cup with a degreased cotton swab. Transfer all the solution to a 50ml EP tube and cut the cotton swab tip into the EP tube. Clean the scissors with the remaining solution. Transfer all the cleaning solution to the same 50ml EP tube. Sonicate for 10 minutes. Take an appropriate amount and filter it through a 0.22μm PTFE needle filter. Collect the filtrate.

[0081] The test results are shown in Table 5.

[0082] Table 5. Cumulative permeation of adapalene gel at different times (1-16).

[0083]

[0084] From Table 5, we can draw the following conclusions:

[0085] 1) Comparing adapalene gels 1-3 and adapalene gels 7-12, it is evident that the cumulative permeation of adapalene gels 1-3 is superior to that of adapalene gels 7-12 at the same time point. Therefore, under the same conditions, controlling the particle size D90 of drug-loaded microspheres 1-3 can effectively improve the in vitro transdermal permeation of adapalene gel. The best in vitro transdermal permeation effect of adapalene gel is achieved when the particle size D90 of drug-loaded microsphere 1 is ≤0.6 mm, the particle size D90 of drug-loaded microsphere 2 is 0.7-1.1 mm, and the particle size D90 of drug-loaded microsphere 3 is 1.2-1.5 mm.

[0086] 2) Comparing adapalene gels 1, 4–6 with adapalene gels 13–16, it is evident that the cumulative permeation of adapalene gels 1, 4–6 is superior to that of adapalene gels 13–16 at the same time point. Therefore, under the same conditions, controlling the particle size D90 of drug-loaded microspheres 1, 4–6 can effectively improve the in vitro transdermal permeation of adapalene gel. When the ratio of drug-loaded microspheres 1, 2, and 3 is (7–8):10:(13–15), the in vitro transdermal permeation effect of adapalene gel is even better.

[0087] Stability tests were conducted on the adapalene gels 1-6 prepared in Examples 1-6 and the reference formulation (licensed by Galderma International).

[0088] Adapalene gels 1–6 and the reference formulation (licensed by Galderma International) were subjected to accelerated treatment at room temperature and 60°C for 30 and 60 days, respectively, and the content of the detected substances was observed. The results are shown in Table 6.

[0089] Table 6. Changes in properties and content of adapalene gels 1-6 and the reference formulation (licensed by Galderma International) after 30 and 60 days of accelerated treatment at room temperature and 60°C, respectively.

[0090]

[0091]

[0092] As can be seen from Table 6, the adapalene gels 1-6 prepared in this invention can still maintain their physical properties and the content of active substances and other related substances relatively stably under high temperature conditions of 60°C. Compared with the reference preparation (licensed by Galderma International), the stability is significantly increased.

[0093] It is understood that the above embodiments are merely exemplary embodiments used to illustrate the principles of this application, and this application is not limited thereto. For those skilled in the art, various modifications and improvements can be made without departing from the spirit and substance of this application, and these modifications and improvements are also considered to be within the scope of protection of this invention.

Claims

1. A gel for treating acne, characterized in that, The product includes drug-loaded microspheres, a matrix, a humectant, an antibacterial agent, and a pH adjuster. The drug-loaded microspheres include a blank microsphere core, adapalene, and a binder. The drug-loaded microspheres include drug-loaded microsphere 1, drug-loaded microsphere 2, and drug-loaded microsphere 3, and the particle size and amount of drug-loaded microspheres 1 to 3 are different.

2. The acne treatment gel according to claim 1, characterized in that, The particle size D90 ranges of the drug-loaded microspheres 1 to 3 are ≤0.6 mm, 0.7 to 1.1 mm, and 1.2 to 1.5 mm, respectively.

3. The acne treatment gel according to claim 1, characterized in that, The ratio of the amount of the drug-loaded microcapsules 1 to 3 is (7 to 8): 10: (13 to 15).

4. The acne treatment gel according to claim 1, characterized in that, The particle size D90 ranges of the drug-loaded microspheres 1 to 3 are 0.4 mm, 0.8 mm, and 1.4 mm, respectively.

5. The acne treatment gel according to claim 1, characterized in that, The dosage ratio of the drug-loaded microcapsules 1 to 3 is 7.1:10:13.

5.

6. The acne treatment gel according to claim 1, characterized in that, The drug-loaded microcapsules 2 include a blank core, adapalene, a binder, a plasticizer, and a pore-forming agent.

7. The acne treatment gel according to claim 1, characterized in that, The drug-loaded microcapsules 3 include a blank core, adapalene, a binder, a plasticizer, and a pore-forming agent.

8. The acne treatment gel according to claim 1, characterized in that, The adhesive is one or more of methylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, polyethylene glycol, and polyvinylpyrrolidone.

9. The acne treatment gel according to claim 1, characterized in that, The blank pellet core is selected from microcrystalline cellulose pellet cores.

10. A method for preparing an acne treatment gel according to claim 1, comprising: 1) Dissolve the binder in purified water to prepare an adhesive aqueous solution. Dissolve the prescribed amount of adapalene in the above adhesive aqueous solution to prepare a coating solution. Coat the blank pellet core, dry and sieve to obtain drug-loaded microparticles 1. Control the particle size D90 of drug-loaded microparticles 1 to be ≤0.6mm. 2) Dissolve the binder in water to prepare an adhesive aqueous solution. Dissolve the prescribed amount of adapalene in the above adhesive aqueous solution to prepare a coating solution. Coat the blank pellet core with the solution, dry and sieve to obtain drug-loaded microparticles 2. Control the particle size D90 of drug-loaded microparticles 2 to be 0.7-1.1 mm. 3) Dissolve the adhesive in water to prepare an adhesive aqueous solution. Dissolve the prescribed amount of adapalene in the above adhesive aqueous solution to prepare a coating solution. Coat the blank pellet core with the solution, dry and sieve to obtain drug-loaded microparticles 3. Control the particle size D90 of the drug-loaded microparticles 3 to be 1.2-1.5 mm. 4) Dissolve the antibacterial agent and humectant in water, add the matrix, stir well, and obtain a mixture; 5) Take a certain amount of the above drug-loaded microspheres 1 to 3, mix them evenly, add them to the mixture prepared in step (4), stir at high speed to homogenize, add pH adjuster to adjust pH to 5 to 6, add water, stir thoroughly, and then obtain adapalene gel.

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