University of the Sciences in Philadelphia, Philadelphia College of Pharmacy, 600 S 43rd Street, Philadelphia, PA 19104, USA.
Int J Pharm. 2010 Jan 29;385(1-2):53-65. doi: 10.1016/j.ijpharm.2009.10.028. Epub 2009 Oct 21.
This study evaluated the potential of coarse ethylcellulose (CPEC) and high molecular weight polyethylene oxide (PEO) as excipients in the production of beads by extrusion-spheronization. CPEC was investigated as a diluent and PEO as an extrusion aid and a binder. Beads were manufactured with caffeine as a model drug. Release studies were conducted, and the bead size, shape, yield, and friability were determined. The effects of formulation and process variables and their interactions were studied by a sequential experimental design based on a response surface method. In the initial stage, a two level half fractional factorial design was employed as a screening design, which was subsequently augmented to a central composite design. Statistical analysis indicated that formulation variables including PEO content, microcrystalline cellulose (MCC) content, and water content, and two process variables, namely spheronizer speed and spheronization time, significantly affected the properties of the beads. Interactions between two factors have significant effects on several of the measured responses. Simultaneous optimization of the responses was conducted and validated by performing experiments at the optimal conditions. Overall, the results confirmed that immediate release, spherical beads with low friability and narrow size distribution could be produced with minimal amounts of MCC.
本研究评估了粗乙基纤维素（CPEC）和高分子量聚乙烯氧化物（PEO）作为挤出造球工艺中辅料的潜力。CPEC 被用作稀释剂，PEO 则作为挤出助剂和粘合剂。以咖啡因作为模型药物来制备微丸。进行了释放研究，并确定了微丸的粒径、形状、收率和脆碎度。通过基于响应面法的序贯实验设计研究了制剂和工艺变量及其相互作用的影响。在初始阶段，采用两水平半析因设计作为筛选设计，随后扩展为中心组合设计。统计分析表明，包括 PEO 含量、微晶纤维素（MCC）含量和水分含量在内的制剂变量以及两个工艺变量，即造粒机速度和造粒时间，显著影响微丸的性质。两个因素之间的相互作用对多个测量响应有显著影响。通过在最佳条件下进行实验，对响应进行了协同优化和验证。总的来说，结果证实了可以用最少量的 MCC 生产出即时释放、低脆碎度和窄粒径分布的球形微丸。
