A clindamycin phosphate peroxide benzoyl gel and a method of preparing the same

Abstract

This invention belongs to the field of pharmaceutical formulation technology and relates to a clindamycin phosphate peroxide gel and its preparation method. The clindamycin phosphate peroxide gel, based on clindamycin, comprises, by mass percentage: 1% clindamycin phosphate, 5% peroxide, 1-3% carbomer, 0.2-1% sodium dioctyl succinate sulfonate, 2-3% transdermal penetration enhancer, 5-15% humectant, 0.05-0.2% preservative, appropriate amount of pH adjuster, and the balance being purified water. The transdermal penetration enhancer is selected from menthol and isopropyl myristate, with a mass ratio of menthol to isopropyl myristate of 1:4-6. This invention solves the problem of low transdermal absorption rates of clindamycin phosphate and peroxide in clindamycin phosphate peroxide gel by screening the types and composition of transdermal penetration enhancers, and the preparation process is simple and can be scaled up for production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a clindamycin phosphate peroxybenzoyl gel and its preparation method. Background Technology

[0002] Acne is a common chronic inflammatory disease of the hair follicles and sebaceous glands, predominantly affecting adolescents but potentially extending into adulthood. It is primarily caused by four core factors: excessive sebum secretion, abnormal follicular keratinization, proliferation of Propionibacterium acnes, and skin inflammation. It not only affects the appearance of the skin but, in severe cases, can lead to acne marks, scars, and permanent damage to hair follicles, significantly impacting the patient's physical and mental health. Currently, there are various clinical treatments for acne, among which topical gel preparations have become the preferred treatment option for mild to moderate acne due to their advantages of direct application to the affected area, minimal systemic side effects, and ease of use.

[0003] Clindamycin phosphate and benzoyl peroxide combination is a classic clinical treatment for acne. Clindamycin phosphate is a lincosamide antibiotic that, after being absorbed through the skin, inhibits the nucleic acid synthesis of Propionibacterium acnes, blocks bacterial proliferation, and reduces local skin inflammation. Benzoyl peroxide is a strong oxidant that releases reactive oxygen species to kill anaerobic Propionibacterium acnes and gently dissolves follicular keratin, unclogging pores. The combination of the two achieves a synergistic effect of antibacterial, anti-inflammatory, and pore-unclogging, avoiding the shortcomings of single-drug therapy, such as narrow antibacterial spectrum, slow onset of action, and easy drug resistance. Clinical application results are significant.

[0004] Currently available commercially available clindamycin phosphate benzoyl peroxide gels have relatively fixed formulations and generally suffer from insufficient transdermal absorption. The barrier effect of the stratum corneum significantly hinders the penetration of the two active ingredients, resulting in low cumulative drug penetration outside the body. Only a small amount of drug can reach the deep lesions of the hair follicle, leading to poor drug bioavailability, a long onset of action, slow resolution of acne inflammation in some patients, and a high recurrence rate.

[0005] To improve transdermal absorption, existing technologies often employ single transdermal penetration enhancers such as conventional ethanol and propylene glycol. However, these enhancers have poor compatibility, limited synergistic penetration-enhancing effects on two active ingredients with different physicochemical properties, and high concentrations can easily cause adverse reactions such as dry skin, stinging, and redness, reducing patient compliance. Current clindamycin phosphate benzoyl peroxide gel suffers from technical bottlenecks including a single transdermal penetration enhancement system, low cumulative permeability of the two components, poor bioavailability, and difficulty in balancing local irritation and efficacy. To address these shortcomings, this invention systematically screens the types and ratios of transdermal penetration enhancers, optimizes the gel penetration enhancement system, synergistically improves the cumulative skin permeability of the two active ingredients, enhances targeted drug therapy, shortens onset time, and reduces the probability of acne recurrence, possessing significant clinical application value and promotional significance. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides a clindamycin phosphate peroxybenzoyl gel and its preparation method. By screening the types and composition of transdermal absorption enhancers, the problem of low transdermal absorption rates of clindamycin phosphate and peroxybenzoyl in clindamycin phosphate peroxybenzoyl gel is solved.

[0007] This invention provides a clindamycin phosphate peroxide benzoyl gel, comprising clindamycin phosphate, peroxide benzoyl, carbomer, sodium dioctyl succinate sulfonate, transdermal penetration enhancer, humectant, preservative, pH adjuster, and purified water, calculated as clindamycin.

[0008] Preferably, the clindamycin phosphate peroxide gel comprises, by weight percentage (based on clindamycin), 1% clindamycin phosphate, 5% peroxide, 0.5-4% carbomer, 0.1-1.2% sodium dioctyl succinate sulfonate, 1-4% transdermal penetration enhancer, 5-20% humectant, 0.01-0.3% preservative, appropriate amount of pH adjuster, and the balance purified water.

[0009] Preferably, the clindamycin phosphate peroxide gel comprises, by weight percentage (based on clindamycin), 1% clindamycin phosphate, 5% peroxide, 1-3% carbomer, 0.2-1% sodium dioctyl succinate sulfonate, 2-3% transdermal penetration enhancer, 5-15% humectant, 0.05-0.2% preservative, appropriate amount of pH adjuster, and the balance being purified water.

[0010] Preferably, the gel matrix carbomer is selected from carbomer 940 and carbomer 980.

[0011] Preferably, the transdermal penetration enhancer is selected from laurocapram, oleic acid, menthol, and isopropyl myristate.

[0012] More preferably, the transdermal penetration enhancer is selected from menthol and isopropyl myristate.

[0013] More preferably, the mass ratio of menthol to isopropyl myristate is 1:4-6.

[0014] Preferably, the moisturizer is selected from glycerin, propylene glycol, and sorbitol.

[0015] Preferably, the preservative is selected from benzoic acid, sodium benzoate, potassium sorbate, benzalkonium chloride, benzalkonium bromide, and parabens.

[0016] Preferably, the pH adjuster is selected from sodium hydroxide and potassium hydroxide.

[0017] Preferably, the pH value of the gel is 5-6.

[0018] The present invention also provides a method for preparing clindamycin phosphate peroxybenzoyl gel, comprising the following steps: (1) preparing a gel matrix: dispersing carbomer in purified water to allow it to swell fully and form a transparent and uniform gel skeleton; (2) adding the main drug and other excipients: adding the prescribed amounts of clindamycin phosphate, peroxybenzoyl, sodium dioctyl succinate sulfonate, transdermal activator, humectant, and preservative to the above gel matrix in sequence and stirring to mix evenly; (3) adjusting pH and filling: adding a pH adjuster to adjust the pH value of the gel and filling to obtain the gel.

[0019] This invention solves the problem of low transdermal absorption rates of clindamycin phosphate and benzoyl peroxide in clindamycin phosphate peroxide gel by screening the types and composition of transdermal absorption promoters. Moreover, the preparation process is simple and can be scaled up for production. Detailed Implementation

[0020] In view of the deficiencies of the prior art, the inventors, through long-term research and extensive practice, have proposed the technical solution of this invention. The invention is further illustrated below by means of embodiments, but these embodiments do not constitute a limitation of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without inventive effort are within the scope of protection of this invention.

[0021] Example 1: Screening of Transdermal Transdermal Enhancers by Type and Composition Preparation method: Disperse Carbomer 940 in purified water and allow it to swell fully to form a transparent and uniform gel matrix; add the prescribed amounts of clindamycin phosphate, benzoyl peroxide, sodium dioctyl succinate sulfonate, transdermal penetration enhancer (not added in prescription 2), humectant, and preservative to the above gel matrix in sequence and stir to mix evenly; add pH adjuster to adjust the pH value of the gel, and fill into containers to obtain the final product.

[0022] The clindamycin phosphate peroxide benzoyl peroxide gels prepared according to prescriptions 1-8 were subjected to in vitro transdermal tests. Rat skin was used in the transdermal tests, and a Franz diffusion cell with a diffusion area of ​​4.8 cm² was employed. 2 The receiving cell had a volume of 13.5 mL. Samples were taken at 1 h, 2 h, 3 h, 6 h, 12 h, and 24 h for testing. The cumulative permeation rates of clindamycin phosphate and benzoyl peroxide over 24 h were calculated. The results of the transdermal test are as follows: The results show that, without the addition of a transdermal penetration enhancer, the cumulative permeation rate of clindamycin phosphate in clindamycin phosphate peroxybenzoyl gel over 24 hours was 0.04%, and the cumulative permeation rate of peroxybenzoyl gel over 24 hours was 1.21%, both of which had low cumulative permeation rates over 24 hours. Formula 3 uses menthol as a transdermal permeability enhancer; Formula 6 replaces menthol with oleic acid. Benzoyl peroxide significantly increases the cumulative permeability at 24 h, but clindamycin phosphate has a lower cumulative permeability at 24 h. Formula 4 uses isopropyl myristate as a transdermal permeability enhancer; Formula 5 replaces menthol with laurocapram; Formula 8 has a menthol to isopropyl myristate mass ratio of 1:7. Clindamycin phosphate has a higher cumulative permeability at 24 h, but benzoyl peroxide has a lower cumulative permeability at 24 h. Formula 7 has a menthol to isopropyl myristate mass ratio of 1:3. Clindamycin phosphate and benzoyl peroxide significantly increase the cumulative permeability at 24 h, but clindamycin phosphate is below 0.5%, and benzoyl peroxide is below 5%. Formula 1 selects menthol and isopropyl myristate as transdermal permeation enhancers, and the mass ratio of menthol to isopropyl myristate is 1:4. The cumulative permeation rate of clindamycin phosphate in the prepared clindamycin phosphate peroxybenzoyl gel over 24 hours exceeds 0.5%, and the cumulative permeation rate of peroxybenzoyl over 24 hours exceeds 5%.

[0023] Example 2 Preparation method: Disperse Carbomer 980 in purified water and allow it to swell fully to form a transparent and uniform gel matrix; add the prescribed amounts of clindamycin phosphate, benzoyl peroxide, sodium dioctyl succinate sulfonate, transdermal penetration enhancer, humectant, and preservative to the above gel matrix in sequence and stir to mix evenly; add pH adjuster to adjust the pH value of the gel, and fill into containers to obtain the final product.

[0024] The clindamycin phosphate peroxide benzoyl gel prepared according to prescriptions 9-13 was subjected to an in vitro transdermal test. Rat skin was used in the transdermal test, and a Franz diffusion cell with a diffusion area of ​​4.8 cm² was employed. 2 The receiving cell had a volume of 13.5 mL. Samples were taken at 1 h, 2 h, 3 h, 6 h, 12 h, and 24 h for testing. The cumulative permeation rates of clindamycin phosphate and benzoyl peroxide over 24 h were calculated. The results of the transdermal test are as follows: The results show that prescriptions 1 and 9-13 selected menthol and isopropyl myristate as transdermal permeation enhancers, and the mass ratio of menthol to isopropyl myristate was 1:4-6. The cumulative permeation rate of clindamycin phosphate and benzoyl peroxide in the prepared clindamycin phosphate peroxide gel was significantly increased over 24 hours, with clindamycin phosphate exceeding 0.5% and benzoyl peroxide exceeding 5%.

[0025] It should be understood that the technical solutions of the present invention are not limited to the specific embodiments described above. Any technical modifications made to the technical solutions of the present invention without departing from the spirit and scope of the claims are within the scope of protection of the present invention.

Claims

1. A clindamycin phosphate peroxybenzoyl gel, characterized in that, The gel comprises, by mass percentage (based on clindamycin), 1% clindamycin phosphate, 5% benzoyl peroxide, 1-3% carbomer, 0.2-1% sodium dioctyl succinate sulfonate, 2-3% transdermal penetration enhancer, 5-15% humectant, 0.05-0.2% preservative, appropriate pH adjuster, and the balance being purified water; the transdermal penetration enhancer is selected from menthol and isopropyl myristate, with a mass ratio of menthol to isopropyl myristate of 1:4-6, and the pH value of the gel is 5-6.

2. The clindamycin phosphate peroxybenzoyl gel according to claim 1, characterized in that, The carbomer is selected from carbomer 940.

3. The clindamycin phosphate peroxybenzoyl gel according to claim 1, characterized in that, The carbomer is selected from carbomer 980.

4. The clindamycin phosphate peroxybenzoyl gel according to any one of claims 1-3, characterized in that, The moisturizer is selected from glycerin, propylene glycol, and sorbitol.

5. The clindamycin phosphate peroxybenzoyl gel according to any one of claims 1-3, characterized in that, The preservatives are selected from benzoic acid, sodium benzoate, potassium sorbate, benzalkonium chloride, benzalkonium bromide, and parabens.

6. The clindamycin phosphate peroxybenzoyl gel according to any one of claims 1-3, characterized in that, The pH adjuster is selected from sodium hydroxide and potassium hydroxide.

7. The clindamycin phosphate peroxybenzoyl gel according to any one of claims 1-3, characterized in that, The pH value of the gel is 5.

5.

8. The method for preparing clindamycin phosphate peroxybenzoyl gel according to any one of claims 1-7, characterized in that, The process includes the following steps: (1) Preparing the gel matrix: Disperse carbomer in purified water and allow it to swell fully to form a transparent and uniform gel skeleton; (2) Adding the active ingredient and other excipients: Add the prescribed amounts of clindamycin phosphate, benzoyl peroxide, sodium dioctyl succinate sulfonate, transdermal penetration enhancer, humectant, and preservative to the above gel matrix in sequence and stir to mix evenly; (3) Adjusting pH and filling: Add pH adjuster to adjust the pH value of the gel and fill it to obtain the final product.

9. The method for preparing clindamycin phosphate peroxybenzoyl gel according to claim 8, characterized in that, Adjust the pH of the gel to 5-6.

10. The method for preparing clindamycin phosphate peroxybenzoyl gel according to claim 9, characterized in that, Adjust the pH of the gel to 5.5.

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