Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ hydrogel based on poloxamer 407 and carrageenan

The objective of this study was to construct a new in situ gel system based on the combination of poloxamer 407 and carrageenan (carrageenan-poloxamer 407 hydrogel, CPH) for intranasal delivery of ketorolac tromethamine. CPH showed potassium ionconcentration-dependent erosion characteristics which ensured slow erosion in aqueous environment containing potassium ion at the physiological level. Loading with ketorolac tromethamine influenced erosion, drug release and thermosensitive properties of CPH. CPH containing 15% ketorolac tromethamine showed suitable gelation temperature (near 35 degrees C) and in vitro sustained release profiles. Pharmacokinetic study of intranasal CPH containing 15% ketorolac tromethamine in rats demonstrated enhanced absolute bioavailability (68.8 +/- 23.3%) and prolonged mean residence time (8.8 +/- 3.5 h) in comparison with the intranasal solution group (24.8 +/- 13.8%, 3.9 +/- 0.6 h). Nasal ciliotoxicity evaluation on an in situ toad palate model preliminarily showed the safety of CPH for intranasal use. All results suggested the potential of CPH as a newsustained-release platform for the intranasal delivery of ketorolac tromethamine. (C) 2014 Elsevier B.V. All rights reserved.