US-12616710-B2 - Topical compositions

Abstract

The disclosure provides a topical gel formulation comprising 1-1.5 wt. % clindamycin phosphate, 2.5-3.5 wt. % benzoyl peroxide, and 0.1-0.2 wt. % adapalene, in combination with a gelling agent, a polyhydric alcohol, and water, useful in treating inflammatory skin conditions, including acne, together with methods of making and using the same.

Inventors

• Varsha Bhatt
• Radhakrishnan Pillai
• Arturo Angel

Assignees

• BAUSCH HEALTH IRELAND LIMITED

Dates

Publication Date

20260505

Application Date

20250723

Claims (4)

1. 1 . A topical gel formulation comprising: 1.2 wt. % clindamycin phosphate; 3.1 wt. % benzoyl peroxide comprising a plurality of benzoyl peroxide particles; 0.15 wt. % adapalene comprising a plurality of adapalene particles; a polyhydric alcohol selected from the group consisting of propylene glycol, ethoxydiglycol, glycerol, and combinations thereof; a gelling agent selected from the group consisting of hydroxypropylcellulose, hydroxyethylcellulose, carboxyvinyl polymers, carboxyvinyl copolymers, polyacrylates, acrylate copolymers, acrylamide/sodium acryloyldimethyltaurate copolymers, methylcellulose, hydroxypropylmethylcellulose, xanthan gum, carrageenan gum, and combinations thereof; and potassium hydroxide, wherein the plurality of benzoyl peroxide particles and the plurality of adapalene particles are uniformly dispersed in the formulation.
2. 2 . The topical gel formulation of claim 1 , wherein the potassium hydroxide is present in an amount to provide a pH of 5-6.
3. 3 . The topical gel formulation of claim 1 , wherein the formulation is stable at room temperature for at least six weeks.
4. 4 . The topical gel formulation of claim 1 , wherein the polyhydric alcohol is propylene glycol.

Description

This application is a continuation of U.S. patent application Ser. No. 18/901,594, filed Sep. 30, 2024, which is a continuation of U.S. patent application Ser. No. 18/639,630, filed Apr. 18, 2024, now U.S. Pat. No. 12,138,278, which is a continuation of U.S. patent application Ser. No. 17/835,935, filed Jun. 8, 2022, now U.S. Pat. No. 12,128,059, which is a continuation of U.S. patent application Ser. No. 16/945,067, filed Jul. 31, 2020, now U.S. Pat. No. 11,389,467, which claims priority to U.S. Provisional Application No. 62/881,836, filed Aug. 1, 2019, the contents of each are incorporated herein by reference in their entireties. FIELD This disclosure relates to topical compositions for the treatment of dermatological conditions, including acne. In particular, the disclosure provides topical compositions comprising three different active ingredients, and methods for making and using the same. BACKGROUND Acne is a very common disorder of sebaceous follicles that is most prevalent among teenagers, usually triggered by the increase in androgen production occurring at puberty. Although acne generally resolves by the age of 25, approximately 3% to 8% of adults 25 to 44 years of age present with acne. The pathogenesis is complex and appears to involve 4 primary features: stimulation of sebum gland activity, bacterial proliferation (especially Cutibacterium acnes, previously known as Propionibacterium acnes), abnormal follicular hyperkeratinization and resultant obstruction of the sebaceous follicles, and the release of inflammatory mediators. These changes in acne patients result in the formation of clinical inflammatory lesions including superficial pustules such as comedones (popularly known as “blackheads” or “whiteheads”) and more deeply located papules, nodules, and cysts. The areas most affected by the disease include the pilosebaceous follicles of the head and upper trunk, where the sebaceous glands are particularly active. Elevated production of oily sebum and keratin, leading to acne, is influenced by individual genetics, a wide variety of medications (e.g., corticosteroids, androgens, or lithium, azathioprine, haloperidol, Vitamin D, Vitamin B12, halogens such as iodides or bromides, phenytoin, or phenobarbital), and possibly other factors, such as diet and stress. Elevated sebum and keratin production correlates with elevated levels of various hormones, including androgens (e.g., testosterone, dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA)), growth hormone (GH), and insulin-like growth factor 1 (IGF-1). Infection of the follicle by anaerobic bacteria (e.g. C. acnes) and/or by the parasitic mite Demodex folliculorum may exacerbate the condition, although whether infection is involved in initiating the condition is unclear. Current treatment options for acne include (i) retinoids and retinoid-like drugs, such as tretinoin (Avita, Retin-A, others), adapalene (Differin) and tazarotene (Tazorac, Avage); antibiotics, including clindamycin with benzoyl peroxide (Benzaclin, Duac, Acanya) and erythromycin with benzoyl peroxide (Benzamycin); salicylic acid and azelaic acid; and dapsone (Aczone). Benzoyl peroxide is commonly found in over-the-counter products to treat acne, and prescription products in combination with antibiotics. While the exact mechanism of action is unclear, it is bacteriocidal, it breaks down keratin, thereby helping to unclog the pores, and it may inhibit sebum production. Benzoyl peroxide formulations, however, may cause local irritation, both because benzoyl peroxide is a powerful oxidant, and because, being nearly insoluble in water, it is often formulated with harsh organic solvents. It is also incompatible with many other compounds, due to its high chemical reactivity. Clindamycin for topical administration may be administered in the form of clindamycin phosphate, a phosphate ester prodrug of clindamycin. In addition to its antibiotic effects, clindamycin has anti-inflammatory effects. One disadvantage of clindamycin (and other antibiotics) is the risk of developing antibiotic-resistant bacterial populations on the skin. Adapalene is a retinoid compound that is an agonist for specific retinoic acid nuclear receptors. It modulates cellular differentiation, keratinization, and inflammatory processes, and topical formulations have been approved for treating acne. Although the exact mode of action of adapalene is unknown, it may normalize the differentiation of follicular epithelial cells, resulting in decreased microcomedone formation. Combination products have been tried, but the results have been quite unpredictable. For example, Bowman, S. et al., “Comparison of clindamycin/benzoyl peroxide, tretinoin plus clindamycin, and the combination of clindamycin/benzoyl peroxide and tretinoin plus clindamycin in the treatment of acne vulgaris: a randomized, blinded study.” J Drugs Dermatol. 2005 September-October; 4(5):611-8, reported that while regimens that included clindamyc