Application of Plackett–Burman screening design for preparing glibenclamide nanoparticles for dissolution enhancement

This study is to improve the dissolution characteristics of a poorly water-soluble drug glibenclamide (GLB), by preparing nanoparticles through liquid anti solvent precipitation. A Plackett–Burman screening design was employed to screen the significant formulation and process variables. A total of 12 experiments were generated by Minitab® 16 for screening 5 independent variables namely the amount of poloxamer 188 (PX) (X1), amount of PVP S 630 D (PD) (X2), solvent to antisolvent volume ratio (S/AS) (X3), amount of GLB (X4) and speed of mixing (X5). Mean particle size (Y1), saturation solubility (Y2) and % dissolution efficiency (%DE5min) (Y3) were selected as response variables. All the regression models yielded a good fit with high determination coefficient and F value. The Pareto chart depicted that all the independent variables except the amount of GLB had a significant effect (p < 0.001) on the response variables. The mathematical model for mean particle size (PS) generated from the regression analysis was given by PS = 830 − 8.14 PX + 12.8 PD − 11.1 S/AS + 1.42 GLB Conc. − 0.676 speed of mixing (R2 = 93.5, Fratio = 17.28, p < 0.001). Prepared GLB nanoparticles exemplified a significant improvement (p < 0.05) in the release as compared to pure GLB with the optimum formulation releasing almost 80% drug within first 5 min. The X-ray diffraction studies concluded that the crystallinity of nanoparticles from the optimum batch was intact and the increased dissolution could be ascribed to conversion of unmilled GLB to nanoparticles.

Plackett-Burman screening design was applied to prepare glibenclamide nanoparticles to improve its dissolution characteristics. Pareto chart revealed that all the predetermined independent variables except drug concentration had a significant effect on the dependent variables. The optimum batch of nanoparticles showed a mean particle size of 279 nm and released almost 80 % drug within first 5 min which is significantly (p < 0.001) higher as compared to pure drug which showed 8.5 % dissolution.Figure optionsDownload as PowerPoint slideHighlights
► Glibenclamide nanoparticles have been prepared using liquid anti solvent precipitation.
► Formulation and process variables were screened by Plackett–Burman screening design.
► Optimum formulation had crystalline drug and released 80% drug within 5 min.
► Plackett–Burman screening design helped in understanding the mechanics of process.
► The improved dissolution of glibenclamide might improve patient compliance.