Prepration And Evaluation Of Ketorolac Tromethamine-loaded In Situ Gel For Intranasal Administration

With advantages like rapid absorption, convenient and avoidance of the first-pass effect, nasal administration has attracted wide attention. In situ gel combines easy administration of solution and long-term retention of gel dose administration and looks charming as novel sustained-release drug delivery. Non-steroidal anti-inflammatory drug ketorolac tromethamine (Ketorolac Tromethamine, Ket) has been widely used in clinic for controlling moderate to severe pain after surgery. Usually it is administered by injection. Recently marketed Ket nasal spray has to be given frequently due to the rapid clearance from the nasal cavity. Hence the objective of this thesis was to prepare and evaluate ketorolac tromethamine-loaded nasal thermosensitive in situ gel (Ket-CPH).In vitro evaluation of Ket-CPH includes hydrogel erosion, drug release and rheology. It was found that Ket-CPH had good thermosensitive phase transition behavior and considerable sustained-release property. CPH containing15%Ket has a suitable gelation temperature at33℃and chosen for further in vivo evaluation.In vivo evaluation of Ket-CPH included pharmacokinetic study and nasal ciliotoxicity. Ket-CPH showed increased AUC, prolonged MRT and similar Tmax in comparison with Ket solution. Nasal ciliotoxicity study suggested that both CPH gel matrix itself and Ket-CPH had no significant ciliotoxicity.In summary, Ket-CPH is a promising nasal formulation which is easy-to-use, safe and favors nasal drug absorption. The present work laid good basis for further application of CPH for nasal administration.