Study On The Preparation Of 2% Butenafine Hydrochloride Cream

Butenafine is a benzylamine derivative with a chemical structure and mode of action similar to allylamines. It has favorable activity against dermatophytes, achieves high concentrations in skin and remains in skin tissue for prolonged periods. Topical butenafine is well-tolerated and adverse reactions are rare. In this paper we prepared 2% butenafine hydrochloride cream including 20% urea as keratolytic. This cream is topically administrated for the treatment of onychomycosis and hasn't come into the market all over the world. By means of selecting right moisturizer, permeation enhancer, solubilizing agent, preservative and optimizing the quantity of emulsification agent, water phase bases and oil phase bases we prepared 2% butenafine hydrochloride O/W cream which was stable and had good appearance and properties. We detected the relative substances of butenafine with the method of TLC, and the content of impurity was less than 2% which was up to the mustard. We determined the contents of butenafine with HPLC and urea with spectrophotometry. The two methods were accuracy and convenient. butenafine and urea average contents of three batches were 101.45% and 98.82%(RSD were 0.75% and 0.64% respectively ) which was conform to the requirement. The stability experimentation showed that after 6 months'accelerated trial and 12 months'long-term trial, the cream's appearance, pH, relative substances and content had no obvious change, thus we temporarily constituted that the validity period of the cream was 24 months when hermetically preserved in room temperature. To study the allergia and irritation of butenafine cream, we applied hair-cut guinea pig with (2%,5%,10%) butenafine cream and applied hair-cut healthy rabbit with 2% butenafine cream one or more times. No anaphylaxis occurred in guinea pig's skin and no irritation reaction occurred in complete skin and injured skin of rabbit. The result indicated that 2% butenafine hydrochloride cream was safe as topical agent. MIC test showed that the antifungal activity of butenafine cream was according with pure butinafine, which meant that vehicle had no influence to the antifungal activity of butinafine. In order to assess the efficacy of butenafine hydrochloride cream, we used it as antifungal agent in vitro in an experimental model of onychomycosis with sheep hoof plates to simulate human nails. The result was that 2% butenafine cream was more effective than 1% and as effective as 3%, so increasing the content of butenafine was not needed. 2% butenafine cream and 5% amorolfine nail lacquer had the same antifungal activity at last, but 2% butenafine cream seemed to take effect more quickly than 5% amorolfine nail lacquer. To sum up,after synthetically assessment of 2% butenafine cream, we can say that it is a safe, effective and stable topical agent for the treatment of onychomycosis and have good marketing promise deserving to popularize.