通过试验设计（DOE）优化多颗粒挤出滚圆工艺.PDFVIP

Optimization of Extrusion Spheronization Process for Multiparticulates via Design of Experiments Gus LaBella AAPS Colorcon, Inc., Harleysille, PA USA Poster Reprint 2016 Purpose This study evaluates the extrusion-spheronization process for preparing drug loaded multiparticulates. Formulation and several processing parameters were evaluated through design of experiments (DOE). The goal was to understand the impact on particle size and distribution, sphericity, friability and yield of the target bead size as compared to a standard sugar sphere product. Methods Four factors: binder level, water level, spheronization speed and, spheronization time, were studied in a Model Robust response surface design with 27 runs using DOE Fusion Pro. Metoprolol, commonly presented as a multiparticulate product, was chosen as the model drug for this study. A drug loading of 40% was selected due to the high solubility of the drug. Starch 1500® , partially pregelatinized starch, was used as the binder in the formulation and varied from 1 – 7%. The balance of the formulation was microcrystalline cellulose (50 micron). 750 g batch sizes were produced using wet granulation in a Glatt VG 25M high shear granulator with a 5 L bowl. Water was sprayed into the granulator with a pneumatic nozzle and pumped at a constant rate for all batches. The wet mass was then extruded through an LCI MG-55 extruder with a 1mm x 1mm dome die. The extrudates were spheronized with different speeds and times using an LCI QJ-400TG spheronizer i tted with a 2 mm friction plate. Resulting beads were dried in a Glatt GPCG-3 l uid bed dryer. Batches were analyzed using a Camsizer P4, dynamic image analyzer and then sieve cut with 16 and 20 US mesh screens representing the target bead size accep