The aim of the present study were (1) to screen seven independent variables (X) including; speed of rotation (X1), amount of chloroform (X2), HLB (X3), PIR amount in buffer (X4), sonication time (X5), total lipid amount (X6), and surfactant cholesterol ratio (X7) using Plackett-Burman design to identify which variables significantly affect the entrapment efficiency (EE%) and in-vitro release (Y) of PIR niosomes; and (2) to optimize the formulation by response surface methodology (RSM). PIR niosomes were prepared by lipid evaporation method and all vesicles were evaluated for their particle size, EE%, and in-vitro drug release. The niosomes appeared as round in shape and size ranged between 97.85 and 161.25nm. EE% was found to be between 20.23% and 37.13%. The release profiles of PIR niosomes occurred in two distinct phases, an initial phase for about 8 hours, followed by slow phase for at least 4 hours. The in-vitro study suggests that higher EE% was related with slow release. The release pattern shown by these formulations were Higuchi diffusion controlled mechanism. RSM showed that X3, X7, and X6 had the main effect on the responses (Y).