chemical engineering research and design 9 0 ( 2 0 1 2 ) 651–657 Contents lists available at SciVerse ScienceDirect Chemical Engineering Research and Design j ourna l ho me page: www.elsevier.com/locate/cherd Optimization of preparation of matrix pellets containing Eudragit ® NE 30D É. Bölcskei a , G. Regdon Jr. a , T. Sovány a , P. Kleinebudde b , K. Pintye-Hódi a,* a Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary b Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine University, Universitätstr. 1, D-40225 Düsseldorf, Germany a b s t r a c t Matrix pellets containing Eudragit NE 30D were produced by extrusion–spheronization, where the critical control points of the process were detected by means of a factorial design. The factors were the quantity of water, the dosing speed, the spheronization speed and the duration of spheronization. The breaking hardness and aspect ratio were measured and the significant factors were determined. On the basis of the results, a new combination of factors was used, which resulted in matrix pellets with the best characteristics. © 2011 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved. Keywords: Extrusion; Spheronization; Formulation; Morphology; Pharmaceuticals; Polymers 1. Introduction Pellets are defined as spherical, free-flowing granules with a narrow size distribution, typically varying between 500 and 1500 m for pharmaceutical applications (Ghebre-Sellassie, 1989). Interest in pellets as a dosage form (filled into hard gelatin capsules or compressed into disintegrating tablets) has increased continuously as their multiparticulate nature offers important pharmacological and technological advantages over conventional single-unit solid dosage forms (Bechgaard and Hagermann, 1978; Follonier and Doelker, 1992; Krämer and Blume, 1994; Ghebre-Sellassie and Knoch, 2002). Several methods are applicable for pellet preparation, the most popular being solution/suspension layering, pow- der layering, direct pelletization with the use of high-shear mixers and conventional or rotary fluid-bed granulators, and extrusion–spheronization. These pelletization techniques have been reviewed in detail in a number of papers (Ghebre- Sellassie and Knoch, 2002; Erkoboni, 2003; Kleinebudde, 1997; Kleinebudde and Knop, 2007; Trivedi et al., 2007). As this survey focuses on the extrusion–spheronization process, this multistep technique is briefly outlined below. Furthermore, extrusion refers only to wet extrusion; melt extrusion and solid-lipid extrusion are not considered. This process involves several distinct preparation phases: a uni- form powder mixture of drug and excipient(s) is wet-massed ∗ Corresponding author. Tel.: +36 62545576; fax: +36 62545571. E-mail address: klara.hodi@pharm.u-szeged.hu (K. Pintye-Hódi). Received 23 May 2011; Received in revised form 5 September 2011; Accepted 8 September 2011 by the addition of a liquid binder, followed by pressing of the moistened mass through an extrusion screen (extrusion) to form cylindrical extrudates, which are subsequently broken into smaller cylindrical rods and rounded into spherical gran- ules by means of a fast-rotating friction plate (spheronization) and finally dried. This process is an efficient technique for the manufacturing of pellets (even for formulations with a high drug load), and allows a high throughput based on the con- tinuous nature of the extrusion process when combined with multiple spheronizers operating in parallel or in series. A com- prehensive review of this technique (Trivedi et al., 2007) details the different steps of the process and the effects of the differ- ent process parameters on the pellet quality at each stage of the extrusion–spheronization process. In view of the specific nature of this process, not all moistened powder mixtures can be successfully extruded and spheronized. Newton (2002) defined the specific requirements for a wetted mass to be suitable for extrusion and spheroniza- tion, based on the pioneering papers of Reynolds (1970) and Conine and Hadley (1970). To allow extrusion, a cohesive plastic mass must be formulated that remains homogeneous during extrusion. The mass must possess inherent fluidity, permitting flow during extrusion, and self-lubricating prop- erties as it passes through the die. The resultant strands of extrudates must not adhere to each other, and must exhibit plasticity so that the shape imposed by the die is maintained. 0263-8762/$ – see front matter © 2011 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.cherd.2011.09.005