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

作者：Shah Sunny R^*; Parikh Rajesh H; Chavda Jayant R; Sheth Navin R

来源：Powder Technology, 2013, 235: 405-411.

DOI：10.1016/j.powtec.2012.10.055

• Glibenclamide
• Liquid antisolvent precipitation
• Dissolution enhancement
• Plackett-Burman screening design

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 (R) 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 (R-2=93.5, F-ratio = 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.

• 出版日期2013-2