BR-112014000178-B1 - Anhydrous Pharmaceutical Composition and Its Use

Abstract

ANHYDROUS PHARMACEUTICAL COMPOSITIONS, PACKAGED NITRIC OXIDE-RELEASING PHARMACEUTICAL GEL, USE AND PRODUCTION PROCESS OF SAID COMPOSITIONS. The present invention relates to anhydrous compositions that include at least one viscosity-increasing agent, at least one organic solvent, and at least one wetting agent. Such compositions may also include at least one active pharmaceutical ingredient (API) and/or at least one water repellent. Related compositions, processes, and kits are also provided.

Inventors

• Ryan Doxey
• Nathan Stasko

Assignees

• NOVAN, INC

Dates

Publication Date

20260310

Application Date

20120703

Priority Date

20110705

Claims (14)

1. 1. Anhydrous pharmaceutical composition, characterized in that it comprises: hydroxypropylcellulose present in the composition at a concentration in the range of 0.1% to 15% by weight of the anhydrous pharmaceutical composition; ethyl alcohol and/or isopropyl alcohol present in the composition at a concentration in the range of 45% to 95% by weight of the anhydrous pharmaceutical composition; hexylene glycol present in the composition at a concentration in the range of 1% to 20% by weight of the anhydrous pharmaceutical composition; cyclomethicone present in the composition at a concentration in the range of 0.5% to 15% by weight of the anhydrous pharmaceutical composition; a diazeniodiolated cocondensed silica particle present in the composition at a concentration in the range of 0.1% to 40% by weight of the anhydrous pharmaceutical composition; wherein the composition is a packaged composition with a shelf life of at least four weeks, in which the composition retains the ability to release a therapeutically effective amount of nitric oxide in a closed package, stored under recommended storage conditions.
2. 2. Anhydrous pharmaceutical composition according to claim 1, characterized in that the composition comprises ethyl alcohol.
3. 3. Anhydrous pharmaceutical composition according to claim 1, characterized in that the composition comprises ethanol.
4. 4. Anhydrous pharmaceutical composition according to claim 1, characterized in that the composition comprises ethyl alcohol and isopropyl alcohol.
5. 5. Anhydrous pharmaceutical composition according to claim 1, characterized in that ethyl alcohol and/or isopropyl alcohol is present in the composition at a concentration in the range of 60% to 95% by weight of the anhydrous pharmaceutical composition.
6. 6. Anhydrous pharmaceutical composition according to claim 1, characterized in that the diazeniodiolated cococondensed silica particle has an average particle size of less than 10 μm.
7. 7. Anhydrous pharmaceutical composition according to claim 1, characterized in that the anhydrous pharmaceutical composition is a suspension and the diazeniodiolated co-condensed silica particle is suspended in the composition.
8. 8. Anhydrous pharmaceutical composition according to claim 1, characterized in that the shelf life is under refrigerated conditions.
9. 9. Anhydrous pharmaceutical composition according to claim 1, characterized in that the shelf life is at least 52 weeks.
10. 10. Anhydrous pharmaceutical composition according to claim 1, characterized in that for at least 30 days, the anhydrous pharmaceutical composition retains the ability to release a therapeutically effective amount of nitric oxide from an opened package when applied as recommended and when stored under the recommended storage conditions.
11. 11. Anhydrous pharmaceutical composition according to claim 1, characterized in that the anhydrous pharmaceutical composition is non-drying and/or non-irritating to an individual's skin.
12. 12. Use of an anhydrous pharmaceutical composition as defined in claim 1, characterized in that it is used in the preparation of a pharmaceutical composition for the treatment of a dermatological condition on a patient's skin.
13. 13. Use according to claim 12, characterized in that the dermatological condition comprises acne.
14. 14. Anhydrous pharmaceutical composition according to claim 1, characterized in that the composition is a topical composition.

Description

PATENT APPLICATION DATA [001] This patent application claims the benefit of U.S. Provisional Patent Application Serial No. 61/504,628, filed July 5, 2011, and U.S. Provisional Patent Application Serial No. 61/610,137, filed March 13, 2012, disclosure of each of which is incorporated herein by reference in its entirety. FIELD OF THE INVENTION [002] The present invention relates to pharmaceutical compositions. In particular, the present invention is directed to anhydrous topical pharmaceutical compositions. BACKGROUND OF THE INVENTION [003] Acne vulgaris is the most common skin disease in the United States of America. It is estimated that 40 to 50 million Americans have acne, including 80% of people between the ages of 11 and 30. The annual direct costs associated with acne treatment exceeded $2.8 billion in 2007, with the majority of such costs being attributed to prescription drugs. In addition, acne causes both physical and psychological effects, including permanent scarring, anxiety, depression, and low self-esteem. Even in cases of mild acne, the social stigma associated with the disease often results in significant emotional distress and other psychological issues. Due to its social impact, the frequency of recurrence, and the maintenance required over a prolonged course of therapy, the American Academy of Dermatologists has recommended that acne vulgaris be reclassified and investigated as a chronic disease. [004] Acne vulgaris results from the complex reciprocal action of four main pathogenic factors: 1) overproduction of sebum by the sebaceous gland; 2) abnormal keratinization in the follicle; 3) colonization of hair follicles by the anaerobic lipophilic bacterium Propionibacterium acnes or P. acnes; and 4) release of inflammatory mediators within the skin. All acne lesions begin when the combination of excess sebum and abnormal epithelial desquamation obstructs a follicle, forming a microscopic lesion known as a microcomedone. The anaerobic lipid-rich environment of the microcomedone provides an ideal location for the proliferation of P. acnes. Each microcomedone can progress to form a non-inflammatory open or closed comedo (commonly referred to as a "blackhead" or a "whitehead," respectively) or an inflammatory lesion that can be further categorized as a pimple, pustule, nodule, or cyst. [005] The complexity of the disease may require multiple treatments that may include oral and topical antimicrobial agents, oral and topical retinoids, oral contraceptives, and other prescription skin cleansers. The most effective therapies for acne are those that can safely target more than one of the primary causes of acne pathogenesis. [006] Antibiotics were the first successful acne treatment due to their antimicrobial and anti-inflammatory properties. Both topical and systemic antibiotics were quite successful, but the prolonged treatment periods required led to the development of resistance in P. acnes and other non-target commensal (and potentially pathogenic) organisms. The combination of antibiotics with topical retinoids targets three of the four main pathogenic factors associated with acne (all except sebum production). Oral retinoid isotretinoin (e.g., Accutane®) is the only drug implicated as affecting all four pathogenic factors associated with acne. However, the severity of its potential side effects (known teratogenic effects and links to depression, psychosis, and suicide) has limited its use and led to several lawsuits. [007] Although the problems associated with isotretinoin are the most serious, all current acne medications have some adverse effects. Most topical treatments lead to dryness, irritation, and peeling of the skin, and oral antibiotics can cause gastrointestinal irritation, skin photosensitivity, headache, dizziness, anemia, bone and joint pain, nausea, and/or depression. [008] The most commonly prescribed drugs for acne are antibiotics, including benzoyl peroxide, clindamycin, and erythromycin, alone or in combination, and retinoids, including adapalene, tretinoin, and tazarotene, alone or in combination with an antibiotic. Treatments may include combination drugs or combination therapies. For example, a retinoid may be prescribed for morning application and an antibiotic for evening application. Each of these commonly prescribed drugs, however, has disadvantages that often reduce the effectiveness of the therapy. [009] For example, benzoyl peroxide may be the most effective topical medication and can result in a rapid reduction in P. acnes. It also does not induce drug resistance in P. acnes and, when combined with other antibiotics, can reduce the rate at which drug resistance develops. However, benzoyl peroxide commonly results in skin irritation and dryness and discolors tissues. Additionally, approximately 2% of patients have an allergic reaction to benzoyl peroxide. [0010] Clindamycin and erythromycin as monotherapies may be limited in efficacy because of the development of dr