Acne vulgaris is a pleomorphic skin disease characterized by blackheads, whiteheads, papules, pustules, and cysts. The lesions are often contaminated with bacteria, which can lead to secondary infections. The appearance of acne ranges from slight skin irritation to pitting. In extreme cases, acne leads to the development of disfiguring scars.
Acne vulgaris presents in differing forms which correlate with disease severity. The three common forms of acne vulgaris are Comedonal, Papulo-pustular and Nodular (Nodulocystic). Comedonal acne is characterized by the presence of open and closed comedoes (noninflammatory lesions). Papulo-pustular acne is characterized by inflammatory lesions 5 mm in diameter or less. Nodular acne consists of inflammatory lesions greater than 5 mm in diameter.
Acne severity is classified as “mild” to “severe,” depending on the types and numbers of lesions present. Mild acne presents as no more than 19 non-inflammatory lesions, no more than 14 inflammatory lesions, or no more than 29 total lesions. Moderate acne presents as 20-100 non-inflammatory lesions with or without 15-50 inflammatory lesions, for a total of between 30 and 125 lesions. Severe acne presents as greater than 100 non-inflammatory lesions, greater than 50 inflammatory lesions, greater than 125 total lesions, or greater than 5 nodules.
Therapeutic approaches to treating acne include prevention of obstruction of the follicular duct, reopening a blocked duct, combating any infecting bacteria, or reducing the thickened sebum, and combinations of these approaches. The horny outer layer of the skin (stratum corneum) is formed of dead cells, composed largely of keratin. Therapeutic agents which act to prevent the obstruction of the follicular duct by the removal of excess keratin are known as keratolytic agents. Salicylic acid, sulfur, and resorcinol have been employed as keratolytic agents in the management of acne for at least 100 years.
The type of therapy administered for the treatment of acne vulgaris varies with the clinical presentation. Topical treatments are standard for comedones and mild- to moderate-papules and pustules. Oral therapies are generally prescribed for moderate- to severe-papules and pustules and nodular acne. Certain oral contraceptives have proven to be safe and effective for the treatment of acne in women, and may be prescribed for women with acne who also desire birth control.
Prescription topical products indicated for the treatment of acne vulgaris include clindamycin phosphate, erythromycin, sodium sulfacetamide, azaleic acid, benzoyl peroxide, trentinoin, adapalene, tazarotene, clindamycin phosphate-benzoyl peroxide, erythromycin-benzoyl peroxide, and clindamycin phosphate-trentinoin.
Clindamycin is a semi-synthetic antibiotic produced by a 7-(S)-chloro-substitution of the 7-(R)-hydroxyl group of the parent compound lincomycin. Clindamycin phosphate is the water-soluble ester of clindamycin and phosphoric acid, which has little or no antibacterial effect in vitro. The compound is rapidly hydrolyzed both in vitro and in vivo to the active compound, clindamycin, and exerts a potent bacteriostatic effect against streptococci, staphylococci, and anaerobic organisms including Bacterioides fragilis and Propionibacterium acnes. Its activity against the anaerobe Propionibacterium acnes may account for its effectiveness in the treatment of acne vulgaris.
At least one clindamycin phosphate (1%) foam for the treatment of acne vulgaris is currently available, but this product has a number of undesirable properties. The foam is fast-breaking, hydroalcoholic, and thermolabile. As a result of the hydroalcoholic vehicle, the formulation can be drying to the skin and messy to apply, as the foam quickly melts at body temperature. It does not contain any pH-stabilizing buffer salts; indeed U.S. Pat. No. 7,141,237 teaches that the incorporation of buffer salts into clindamycin phosphate foam formulations leads to a dramatic and undesirable increase in the hydrolysis rate of clindamycin phosphate.
Consequently, there exists a need for a clindamycin phosphate foam that is non-drying and not messy, has a suitable melting point, and may be easily applied to the skin.