International Journal of Pharmaceutics 448 (2013) 320–326 Contents lists available at SciVerse ScienceDirect International Journal of Pharmaceutics journa l h o me pag e: www.elsevier.com/locate/ijpharm Effect of temperature increase during the tableting of pharmaceutical materials Marco Cespi a , Giulia Bonacucina a , Luca Casettari b , Sara Ronchi c , Giovanni Filippo Palmieri a,∗ a University of Camerino, School of Pharmacy, Camerino, MC, Italy b University of Urbino, Department of Biomolecular Sciences, Urbino, PU, Italy c Officine meccaniche f.lli Ronchi, Viale Brianza 185, Cinisello Balsamo, MI, Italy 1 a r t i c l e i n f o Article history: Received 24 January 2013 Received in revised form 28 February 2013 Accepted 1 March 2013 Available online 19 March 2013 Keywords: Compaction scale-up Instrumented tableting machine Dynamic mechanical thermal analysis (DMA TDMA) Heckel analysis Tensile strength a b s t r a c t Scale-up of tableting process is particularly difficult due to specific concerns related exclusively to the process itself and that cannot be determined on a smaller scale, which are the effect of compression speed and the build-up of heat due to the length of the compaction operations. In this work, it has been simulated the rise of temperature observed during the tablets manufacturing in a full production scale by means of an appropriate modification of a R&D rotary tablet machine. Four common pharmaceutical excipients, characterized by different chemical nature, consolidation behaviour and temperature sensitiveness have been analysed in terms of compaction mechanism (Heckel and energy analysis) and tabletability, in order to verify any effect of the increase of temperature. The results showed a relevance of the temperature on mechanical tablets properties only on materials characterized by low temperature thermal transitions (melting or glass transition), while, for compounds which do not exhibit thermal events at low temperature, it becomes less important for ductile materials and irrelevant for brittle materials. Heckel analysis highlighted a noticeable increase of ductility only in those materials whose tablets mechanical properties depended on the temperature. On the other hand, energy analysis showed low sensitivity failing to identify any temperature effect on compaction materials properties. This work showed how to simulate the process of temperature rise on a small scale and the influence of temperature on materials compaction properties. The use of a modified tableting machine, able to control the temperature and moisture levels and also capable of monitoring the punch movements, resulted in identifying the effect of temperature both on mechanical and compaction properties on materials. Thus, it represents a valuable tool in order to provide useful information at an early stage during the development of tablets formulations. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Process scale-up deals with the procedures of transferring the results obtained on laboratory scale to the pilot plant and finally to production scale and it is the consequence of the scale dependency of many engineering process. The scale-up issue can be rationally solved applying the analy- sis of similarities among different scales. These approaches, named dimensional analysis, are based on the recognition that a mathe- matical description of a physico-technological problem can be of ∗ Corresponding author at: Via Sant’Agostino No. 1, 62032 Camerino, MC, Italy. Tel.: +39 0737402289; fax: +39 0737637345. E-mail address: gianfilippo.palmieri@unicam.it (G.F. Palmieri). 1 www.officineronchi.it. general validity only when the process equation is dimensionally homogenous, which means that it must be valid in any system of dimensions (Zlokarnik, 2001). Dimensional analysis has been used in the scale-up of a sev- eral pharmaceutical processes, as blending, drying, granulation, grinding, etc. and a large collection of literature in pharmaceutical process scale-up can be found (Levin, 2001). However, dimensional analysis is difficult to apply for some processes, as for example in tableting. The scale-up of compaction shows several specific con- cerns related exclusively to the compaction step and that cannot be determined on a smaller scale, such as the compression speed and the build-up of heat due to the length of the compaction oper- ations (Schwartz, 2001). The speed problem can be solved using specific devices, named “compaction simulators”, able to simulate the high speed compaction processes, typical of a production rotary machines, using small amount of material (Celik and Marshal, 1989; 0378-5173/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijpharm.2013.03.014