Patent Publication Number: US-4482539-A

Title: Betamethasone dipropionate cream

Description:
This invention relates to an elegant cream-like formulation of betamethasone dipropionate. 
     A betamethasone dipropionate cream has been sold by Schering Corporation under the trademark Diprosone. That product consists of betamethasone dipropionate in a cream consisting of purified water, mineral oil, white petrolatum, polyethylene glycol 1000 monocetyl ether, cetostearyl alcohol, monobasic sodium phosphate and phosphoric acid, with 4-chloro-m-cresol and propylene glycol as preservatives. 
     The formulation of the present invention is remarkably simple compared to Diprosone cream. It contains a glycol solvent as a major component, but it is free of any other preservative and contains no surfactants. It is thus less likely to cause allergic reactions due to these additives. Nevertheless, the formulation of the present invention is hightly efficacous and is stable. In fact, it is surprisingly more effective than Diprosone cream. Also, even though standard preservatives are not present, the present formulation has been found to be self preserving when tested in standardized assays for the determination of growth of Eschericia coli, Candida albicans, Staphylococcus aureus, Aspergillis niger, and Pseudomonas aeruginosa. In standard dermal irriration studies on rabbits, the formulation of the present invention has been found to be less irritating than Diprosone cream. 
     The formulation of this invention is of value in the topical treatment of dermatological disorders that are responsive to corticosteroids. Included within this category are disorders such as psoriasis, contact dermatitis, atopic dermatitis and eczema. Treatment with the formulation of this invention is usually accomplished by applying the cream-like gel to completely cover the affected area. The usual frequency of application is twice daily, although adequate maintenance therapy for some patients may be achieved with less frequent application. 
     The formulation of the present invention consists essentially of about 0.02 to 0.10 percent betamethasone dipropionate, about 0.4 to 0.6 percent titanium dioxide, about 1.0 to 2.5 percent Carbomer 940, sufficient base to maintain the pH to between pH 4.0 and pH 5.5, and about 60 to 80 percent of propylene glycol and about 20 to 40 percent water (all percentages are by weight). 
     In a preferred aspect of the present invention, 0.06 to 0.08 betamethasone dipropionate is employed; 65 to 75 percent of propylene glycol and 25 to 35 percent water. The preferred based is sodium hydroxide. 
     Carbomer 940 is an acrylic acid polymer having an approximate molecular weight of 4,000,000. It is available from B. F. Goodrich Chemical Company of as Corbopol 940 resin. 
     This formulation results in an elegant cream-like gel. The use of this formulation is particularly advantageous as the formulation has the desired appearance of a cream but is more easily applied than a gel while it is surprisingly more effective than the Diprosone cream known in the art. 
     The cream-like gel of the present invention is manufactured in a conventional manner by thoroughly mixing the ingredients at ambient or elevated temperatures. Preferably, the betamethasone dipropionate, dissolved in a portion of propylene glycol, is added to the cream-like gel. The ingredients are thoroughly mixed so that the product is homogenous. If desired, additional mechanical agitation can be used as an intermediate or final step in the manufacturing process to impart more homogeneity or improve texture. Processing equipment suitable for these steps is known and includes heat exchangers, propeller mixers, colloid mills, homogenizers, roller mills and the like. 
     The following formulation examples illustrate the compositions of the present invention. It will be apparent to those skilled in the art that many modifications thereof may be practiced without departing from the purpose and intent of this disclosure. 
    
    
     EXAMPLE 1 
     
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Betamethasone Dipropionate Cream                                          
                     Formulation (mg/g)                                   
Ingredients          I       II      III                                  
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Betamethasone 17, 21-dipropionate                                         
                     0.7     0.7     1.0                                  
USP                                                                       
Titanium Dioxide USP 5.0     5.0     5.0                                  
Carbomer 940         20.0    15.0    15.0                                 
Sodium Hydroxide USP 0.4     0.3     0.3                                  
Propylene Glycol USP 700.0   700.0   800.00                               
Purified Water USP   273.9   279.0   178.7                                
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