Pharmaceutical Cream Compositions and Methods of Use

Abstract

Embodiments relating to cream formulations as well as oxymetazoline creams and methods for treating rosacea and symptoms associated with rosacea, including, for example, papules, pustules, phymas (skin thickening), telangiectasias or erythema associated with rosacea, other skin erythemas, telangiectasias, purpura or the like, and other manifestations associated therewith; other inflammatory conditions of the skin including, but not limited to, keratosis pilaris, lupus miliaris dissemniatus faciei, eczema, dermatitis, such as contact dermatitis, atopic dermatitis, seborrheic dermatitis, nummular dermatitis, generalized exfoliative dermatitis, statis dermatitis, neurodermatitis, lichen simplex chronicus, xerosis and xerotic dermatitis, dyshidrosis and dyshidrotic dermatitis, asteototic dermatitis or other conditions characterized by sensitive skin or a disturbance of the epidermal barrier; disorders characterized by rough, dry, cracked or fissured skin, disorders characterized by hyperkeratotic skin such as keratodermas and ichthyosisis and ichthyosiform dermatoses; disorders of hair follicles and sebaceous glands, such as acne, perioral dermatitis, and pseudofolliculitis barbae; disorders of sweat glands, such as miliaria, including, but not limited to, miliaria crystallina, miliaria rubra, miliaria profunda, miliaria pustulosa; sunburn, chronic actinic damage, poikiloderma, radiation dermatitis, actinic purpura (“solar purpura”); other inflammatory dermatoses, reactions and conditions of the skin, including, but not limited to, psoriasis, drug eruptions, erythema multiforme, erythema nodosum, and granuloma annulare; diseases and conditions characterized by bleeding or bruising such as petechiae, ecchymosis, purpura and the like including any accumulation of blood in the skin due to vascular extravasation, irrespective of size or cause, bleeding or bruising due to any skin injury which may include any trauma including surgical or procedural trauma; infection, inflammatory dermatoses or inflammation due to any cause using such creams are described herein.

1 . A pharmaceutical composition comprising oxymetazoline, an emulsifier and an emollient, wherein the composition is a cream. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the oxymetazoline is present in an amount of from about 0.0075% to about 5% by weight. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the emulsifier is present in an amount of from about 1% to about 30% by weight. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the emollient is present in an amount of from about 1% to about 50% by weight. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the emulsifier has a hydrophilic-lipophilic balance of about 9.0 to about 17.0. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the emulsifier comprises a PEG-stearate, a glycol stearate or a mixture thereof. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the emulsifier is polyethylene glycol 6 (PEG-6), polyethylene glycol 32 (PEG-32), and glycol stearate. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the emulsifier comprises ethoxylated fatty acids. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the emollient comprises cetostearyl alcohol. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein a ratio of the emulsifier to the emollient comprises from about 0.7:1 to about 1.8:1. 
     
     
         11 . The pharmaceutical composition of  claim 1 , further comprising an additive selected from the group consisting of preservatives, emulsion stabilizers, pH adjusters, chelating agents, viscosity modifiers, anti-oxidants, surfactants, emollients, opacifying agents, skin conditioners, buffers, and combinations thereof. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the composition further comprises a topically active pharmaceutical agent selected from the group consisting of an antimycobacterial agent, an anti-rosacea agent, and a mixture thereof. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the composition comprises a pH from about 2.0 to about 7.0 at room temperature. 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the pH is unchanged after about 4 weeks storage at about 25° C./60% RH, about 30° C./75% RH or about 40° C./75% RH. 
     
     
         15 . The pharmaceutical composition of  claim 1 , wherein the pH is unchanged after about 1 week storage at about 60° C. 
     
     
         16 . The pharmaceutical composition of  claim 1 , further comprising a vasoconstrictor. 
     
     
         17 . The pharmaceutical composition of  claim 1 , further comprising one or more components selected from:
 one or more preservatives in an amount of from about 0.01% to about 5% by weight of the pharmaceutical composition;   one or more chelating agents in an amount of about 0.001% to about 2% by weight of the pharmaceutical composition;   one or more viscosity modifiers in an amount of from about 0.5% to about 30% by weight of the pharmaceutical composition;   one or more antioxidants in an amount of from about 0.01% to about 3% by weight of the pharmaceutical composition;   one or more surfactants in an amount of from about 0.1% to about 50% by weight of the pharmaceutical composition;   one or more opacifying agents in an amount of from about 0.01% to about 20% by weight of the pharmaceutical composition;   one or more skin conditioners in an amount of from about 1% to about 50% by weight of the pharmaceutical composition;   one or more pH regulators in an amount sufficient to provide a pH of from about 2.5 to about 7.0 for the pharmaceutical composition; and   combinations thereof.