Enhanced dissolution of silymarin/polyvinylpyrrolidone solid dispersion pellets prepared by a one-step fluid-bed coating technique

Solid dispersion systems have been widely used to enhance the dissolution and oral bioavailability of poorly water-soluble drugs. However, the formulation process development and scaling-up present a number of difficulties greatly limiting the commercial applications. In this study, solid dispersions of silymarin (SM) with polyvinylpyrrolidone (PVP) were prepared by a one-step fluid-bed coating technique. The process involved the spray application of the ethyl alcohol solution of SM and PVP and subsequent deposition of the coprecipitates onto the non-pareil pellets in drying air flow in a fluid-bed coater. The central composite design/response surface methodology was employed to investigate the effects of the two independent variables, PVP/SM ratio and coating weight gain, on the dissolution of SM. The results demonstrated that the dissolution of PVP/SM solid dispersions was enhanced greatly at PVP/SM ratios of over 4/1. The results of the central composite design suggested that both PVP/SM ratio and coating weight gain affected the dissolution rate significantly. Second-order or third-order polynomial non-linear equations were employed to estimate the relationship between dissolution responses and the two independent variables. Response surface graphs were delineated based on the best-of-fit equations and the optimal experimental range was identified as: PVP/SM, 4/1−5/1; coating weight gain, 80%−120%. The results indicate that the fluid-bed coating technique has the potential use in the preparation of solid dispersions.

Solid dispersion was prepared by a one-step fluid-bed coating technique. This method was very simple and easy to scale up. Enhanced dissolution of the model drug silymarin was observed at a PVP/silymarin ratio of over 4/1.Figure optionsDownload as PowerPoint slide