The Investigation Of Ketorolac Tromethamine Transdermal Delivery System And Its Preliminary Evaluation

Ketorolac tromethamine is a new kind of non-steroidal drugs with potent analgesic activity,it will be a useful alternative to opioid agents in postsurgical pain and other inflammatory pain.Ketorolac tromethamine is a drug of weak base weak acid salt.The existed dosage forms are capsules,eye drops and injections.But frequent oral administration may cause gastrointestinal side effects,while short half-life and inconvenient administration appears following injection,therefore its clinical application are limited.The transdermal delivery system of ketorolac tromethamine for local inflammatory pain is a new approach which is beneficial for the locally drug concentration,avoiding the side effects of NSAIDs,improving patient compliance and security.Firstly,HPLC method was established for analysis of ketorolac tromethamine in vitro.Simultaneously,the effects of pH on the penetration of KT were studied.Secondly,the effects of different transdermal dosage forms were studied and selected.Thirdly,the prescription and preparation process of KT gel was optimized and its quality were also inspected.At last the analgesic effect of KT gel was measured by phannacodynamies text.The result showed that the KT gel was stable,safe and beneficial to local pain.This paper consisted of five parts.The first chapter introduced background and significance of the work.In the second chapter HPLC method was established for analysis of ketorolac tromethamine in vitro.The solubility and oil/water partition coefficient of ketorolac tromethamine were determined.The effects of pH on the penetration of drug were also studied.In the third chapter,different transdermal dosage forms were preparation and studied its character and quality inspection.It was shown that the permeation kinetics of KT gel had the best steady-state flux,gels was selected as a suitable dosage form for ketorolac tromethamine.In the fourth chapter,On the basis of the studies mentioned above,using carbomer 934 as gel matrix,the optimal formulation of KT gel was acquired by single factor text,such as humectants,pH adjuster,and penetration enhancers.The optimum prescription is optimized by the index of accumulated amount: 1% ketorolac tromethamine,0.9% carbomer 934,5% glycerol,10% ethanol,0.06% menthol,2.5% water soluble Azone,2.5% urea,an appropriate amount of sodium hydroxide solution and purified water.The prepared KT gel fit the requirement on gels regulated by Chinese Pharmacopoeia.KT gel percutaneous permeation process accorded with Higuchi equation.The fifth chapter was pharmacodynamics preliminary study.Acetic-induced body writhing text on mice was used to investigate the analgesic of KT gel.The result of experiment showed that the gels had excellent analgesic effect.Ketorolac tromethamine gel could increase the local concentration of drug,with a high degree of security and good convenience,reduce the gastrointestinal tract and the body of the organizations organ toxicity.Thus KT gel is a safe transdermal delivery system.