Thermosetting gels with modulated gelation temperature for ophthalmic use: the rheological and gamma scintigraphic studies

For ophthalmic drug delivery, Pluronic F127 solutions have a phase transition temperature too low for them to be instilled into the eye at room temperature. Refrigerator storage is usually required to make administration easier, whereas the potential irritation of cold to the sensitive ocular tissues may result in poor topical bioavailability. The purpose of this study is to develop a thermosetting gel with a suitable phase transition temperature by combining Pluronic analogs and to examine the influence of incorporating mucoadhesive polysaccharide, sodium hyaluronate (HA-Na), on the ocular retention of the gel. Dynamic rheological method and single photon emission computing tomography (SPECT) technique were used to ex/in vivo evaluate the thermosetting gels, respectively. An optimized formulation containing 21% F127 and 10% F68 increased the phase transition temperature by 9degreesC as evaluated by elasticity modulus compared to that of individual 21% F127 solution. Rheological behaviors of the Pluronic solutions showed that the combined Pluronic formulation was free flowing liquid below 25degreesC and converted to a firm gel under the physiological condition. Furthermore, this formulation possessed the highest viscosity both before and after tear dilution at 35degreesC. Gamma scintigraphic data demonstrated that the clearance of the thermosetting gel labeled with Tc-99m-DTPA was significantly delayed with respect to the phosphate buffered solution, and at least a threefold increase of the corneal residence time was achieved. However, no further improvement in the ocular retention was observed when adding HA-Na into the thermosetting gel due to the substantially decreased gel strength. (C) 2002 Elsevier Science B.V. All rights reserved.