Preparation And Evaluation Of Compound Ketoconazole Ointment

Superficial fungal disease is a kind of fungal infection in epidermis,skin deck,mucous membrane and hair caused by pathogenic gungi which parasitic in keratin tissue.Primary fungi included skin ringworm fungi,candida and marla color bacteria etc.This kind of disease is the most common infectious diseases of dermatological department,the incidence of tinea manus,tinea pedis and tinea cruris are much higher,and it seriously affect the patient's quality of life.Presently treatmentof superficial fungal disease is achieved by topical anti fungal drugs and oral antifungal drugs or together,the former one can act directly on the site,and it has many advantages such as rapid onset,higher concentration of drugs in the inflammatory tissues,lower systemic side effects.The current clinical used topical antifungal preparations such as clotrimazole ointment,miconazole nitrate ointment and biphenyl benzyl azole ointment,which have poor effect on fungal infections associated with bacterial infections,erosion type between toes,khan brothers tinea sorestype's treatment.Moreover,they can hardly solve the problems of inflammation and itching,and the recurrence rate is high.Therefore,this subject proposed to use ketoconazole as topical antifungal drug,mupirocin as topical antibiotics,mometasone furoate as topical glucocorticoid to prepare one kind of compound preparation to avoid those problems..In this study,HPLC analysis for the mupirocin,mometasone and ketoconazole in compound ketoconazole ointment was established,so was the content of these three drugs in percutaneous penetration experiment.Mobile phase was methanol-pH 5.5 phosphate buffer(65:35).This method is simple and accurate with higher sensitivity and less interference factors.The ratio of bases and the concentration of antioxidant in the compound ketoconazole ointment were optimized with appearance and stability as the indicators.The optimal permeation promoter was achieved.The in-vitro peractaneous penetration assay used vertical Franz diffusion cell,and isolated SD mice belly skin as in-vitro transdermal barrier and polyethylene glycol 400(PEG400)-saline isotomic(60:40)as receptor fluid.Different kind of penetration enhancers were evaluated and compared with the cumulative permeation as the indicators.The final prescription is determined as follows: 2g of ketoconazole,2g of mupirocin,0.1g of mometasone furoate,60.27 g of PEG400,30.13 g of PEG3350,5g of propylene glycol,0.5g of ascorbic acid palmitate.The compound ketoconazole ointment had favorable appearance,consistency,spreadability and transdermal permeation.Compared to commercial preparations,our compound ketoconazole ointment showed obvious antibacterial activity towards the Dermatophyte?Fonsecaea pedrosoi?Staphylococcus aureus.The result of impact factor tests showed that high humidity and illumination had no effect on sealed compound ketoconazole ointment,but high temperature caused loss of the drugs.In the 6 months,accelerated assay and long-term assay,all the indicators of compound ketoconazole ointment showed no significant change,indicating excellent stability and quality.The long-term test is still on going.Preclinical safety experiments were conductedbyusing animal skin irritation test,showing that compound ketoconazole ointment hadnoskin irritation or allergic reactiononit.