Poloxamer 407-based Floating Hydrogels for Intravesical Instillation: Statistical Optimization Using Central Composite Design, Gel Erosion, and Drug Release

Abstract

Poloxamer 407 (POL) is widely used as a thermosensitive hydrogel for intravesical instillation. When POL hydrogel is instilled in the bladder, several problems, including urinary tract obstruction, are observed. To overcome this problem, a POL-based floating hydrogel (PFH) system was developed. Sodium bicarbonate (BC) was used as a floating agent. PFH was optimized using a central composite design with two independent variables (X-1 [POL concentration, 42.43%] and X-2 [BC concentration, 5.23%]) and three response factors (Y-1 [floating time, 240.33 s], Y-2 [duration time, 270 min], and Y-3 [viscosity, 110.39 Pa(.)s]). In gel erosion and drug-release studies in vitro, the remaining PFH fraction decreased exponentially with time, while gemcitabine release was biphasic and surface erosion-controlled. A plot of drug release versus gel erosion showed good linearity. Visual observation for floating, gel duration, and dye release supported the time-course behaviors of the PFH, indicating its usefulness in intravesical instillation.