【正文】 act The position of vehicle on the reversible sol– gel transition temperature in a ternary system made up of methylcellulose (MC), polyethylene glycol (PEG), and citric acid (SC) was investigated. The properties of the in situ gelling system were estimated by rheological measurement. When PEG (4000) concentration was varied from 0% to 10% while MC (SM25) and SC concentrations were kept constant at % and %, respectively, the reversible sol– gel transition temperature lowered from 38 _C to 26 _C with increasing PEG concentration. However, the extent of lowering in temperature was not influenced by the molecular weight of PEG. The reversible sol– gel transition temperature shifted towards the lower temperature with increasing MC concentration, and towards the higher temperature with decreasing pH. Comparison of rheological properties between the present thermosetting in situ gelling solution and a conventional one, such as gellan gum solution or Poloxamer 407 solution, revealed that the present solution radically differed from the conventional solutions in the incipient gelling mechanism. These findings suggest that the ternary system in this study would be useful as a drug delivery system for instillation of drugs into the eye. Keywords Thermosetting gel Sol– gel transition temperature Rheology Methylcellulose– polyethylene glycol– citric acid ternary system Introduction Studies have been made to improve the poor bioavailability of ophthalmic solutions in the eye using various drug delivery systems [1, 2]. For example, polymers gain in viscosity when dissolved and this property is utilized. Thus, attempts were made to prolong the duration of effect by adding a polymer to the ophthalmic solution, thereby increasing precorneal residence time of the drug and improving the keratoconjunctival permeability. The use of biopatible polymers was found to be effective, because they increased the utility of the preparation [3]. However, the use of polymers also has disadvantages, such as difficulty in instillation and disfort after instillation due to the high viscosity of the solution. We recently found a thermosetting gel vehicle that underwent sol– gel transition at around the human eye surface temperature (35 _C [4, 5]) by application of the methylcellulose– polyethylene glycol– citric acid ternary system, and developed a longacting ophthalmic solution (Rysmon TG) containing timolol maleate that is used in the treatment of glaua [6]. It was reported that the ade reagents by Wako Pure Chemical Industries (Japan). The gellan gum used was Gelrite by Wako Pure Clongacting ophthalmic solution exhibited thixotropy at temperatures of 32 _C and upward, showing marked changes in flow curve and viscosity curve with rising temperature . It has been reported that the rheological characteristics of ophthalmic solutions greatly influence the precorneal residence time and the feel to the eye [7]. However, there has been almost no research which examined the properties of various polymer solutions from the viewpoint of rheology. The present study aimed at assessing the effect of the position of a thermosetting gel solution vehicle on its rheological properties. Furthermore, rheological properties were pared among different solutions, with the other in situ gelling systems for ophthalmic use as control. Experimental Materials Four different kinds of methylcellulose (MC), that is, Metolose (SM 15, 25, 400, 1500) by ShinEtsu Chemical (Japan) were used. Polyethylene glycol 1000 (mean molecular weight 950– 1050), 4000 (mean molecular weight 2600– 3800), 6000 (mean molecular weight 7300– 9300) (to be abbreviated to PEG 1000, 4000, 6000) and sodium citrate dihydrate (SC) were special grhemical Industries (Japan), and Poloxamer 407 used was Lutrol F127 by BASF (Japan). Timolol maleate was purchased from Industrie Chemiche Italiane (Italy), ketotifen fumarate from Kyowa Yakuhin Kogyo (Japan), Ofloxacin from Sigma (Japan), and betamethasone sod