Pharmaceutical Studies On Compound Ketoconazole Pet Shampoo

With the development of economic and pets industry, the requirement of animal health drug is more and more. Compound ketoconazole pet shampoo is a compound formulation which consists of 1% ketoconazole and 2% chlorhexidine gluconate. It will be used for prevention and treatment of fungal and bacteria dermatosis for dog and cat. Under the Guidance of Provision for New Animal Drug Approval and Keto-Chlor shampoo, compound ketoconazole pet shampoo has been studied on preparing technology, formulation choosing, determination of content, preliminary stability and quality standard.Compound ketoconazole pet shampoo was preparationed by cold admixture. The best formulation of compound ketoconazole pet shampoo was screened by orthogonal design. Orthogonal design was utilized to optimize the 4 factors in the compound ketoconazole shampoo, namely the antioxidant anhydrous sodium sulfite, sodium lauryl sulfate, fatty alcohol polyoxyethylene lauryl ether sulfate sodium, dodecyl betaine. And the results were anhydrous sodium sulfite 0.2%, sodium lauryl sulfate 7%, fatty alcohol polyoxyethylene lauryl ether sulfate sodium 12% and dodecyl betaine 4%.The quality standard of compound ketoconazole pet shampoo was studied and to establish a HPLC method for the simultaneous determination of ketoconazole and chlorhexidine gluconate in shampoo. The shampoo sample was diluted to suitable concentration with mobile phase, and filtered with microbore membrane. The HPLC system was consisted of Inertsil ODS-3(5μm, 150mm×4.6mm), column temperature was at 40℃, and mobile phase was composed of acetonitrile-0.1mol/L dipotassium hydrogen phosphate (65∶135), adjust pH to 3.2 by phosphoric acid. The flow rate was 1.0mL/min, detection wavelength was at 235nm. The results show that both of the ketoconazole and chlorhexidine gluconate were fine linear in the range of 1 - 100μg/mL respectively, and standard curve and coefficient were Y_KCZ=34331X+16638 (r=0.9999) and Y_Chlo-G= 32349X+6523.6 (r=0.9999) respectively. Intra-day and extra-day RSD values of ketoconazole were less than 1.5% and 2.1%. And intra-day and extra-day RSD values of chlorhexidine gluconate were less than 1.8% and 2.1% respectively. The recoverise of ketoconazole and chlorhexidine gluconate in control shampoo were 99.46%, 99.60%, 99.97% and 100.32%, 98.79%, 100.34% respectively, and both RSD values of the drug were less than 1.7%.Quality of the three groups compound ketoconazole pet shampoo samples were determined by HPLC, and the results were 100.84%, 100.45%, 99.88% and 93.28%, 95.05%, 94.99% respectively, and suit to China Veterinary Drugs Pharmacopeia.Preliminary stability tests showed that the compound ketoconazole shampoo pet for is stable during 6 months in 25℃±2℃, correspond humidity 60%±10% and during 3 months in 40℃±2℃, correspond humidity 70%±10%. Results of quality determination of ketoconazole and chlorhexidine gluconate in compound shampoo were 90%～110%.The preparation method of compound ketoconazole pet shampoo was simple and the quality was stable. The HPLC method of quality determination was easy and suitalbe and sensitivity and specificity. It's well adapted for quality control of compound ketoconazole pet shampoo.