Preparation and characterisation of free flowing solid lipid based drug delivery systems using a twin screw extruder

摘要

In this study, a continuous manufacturing process was developed for adsorbing liquid self-emulsifying drug delivery system (SEDDS) on mesoporous silica carriers in order to produce solid free flowing SEDDS powders. An optimized liquid SEDDS, consisting of Labrafil M 1944 CS, Labrasol and Capryol 90 (15, 80, 5 %w/w), was developed. The formulation spontaneously formed a homogenous emulsion with a droplet size of less than 200 nm (in water) and possessed pH robustness (pH 1.2, pH 6.8). Two grades of mesoporous silica were investigated as solid carriers, namely Syloid XDP 3050 and 3150. A twin screw extruder, setup in the granulation configuration, was employed to assess the mixing and adsorption of liquid SEDDS onto silica particles in a continuous process. Screw configuration, ratio of solid carrier to liquid SEDDS, powder and liquid feed rates and screw speed were identified as important parameters. These parameters were tested and optimized to achieve free flowing solid SEDDS. The maximum lipid loading of Syloid XDP 3050 and 3150 was 1:2 and 1:2 to less than 1:3 ratios, respectively. Although increasing liquid SEDDS loading increased the cohesive properties of the silica particles, the resulting powders afforded acceptable flow rate indexes as determined by powder rheometry. Similar self-emulsification behaviour was observed for solid and liquid SEDDS. With increasing lipid loading, the droplet size of emulsified solid SEDDS increased and changed from a unimodal to a bimodal size distributions. This effect was more pronounced for Syloid XDP3050. Syloid XDP 3150 was less sensitive to droplet size changes as its z-average diameters at 1:2-1:3 ratio were similar to the optimized liquid SEDDS. Targeting a lipid loading ratio of 2:1, process parameters were varied to maximise material throughput. The investigated continuous process of adsorbing liquid SEDDs onto solid carriers produced solid SEDDS with good flow properties. Syloid XDP 3150 seemed more robust to the process than Syloid XDP 3050.