Effect of roll-compaction and milling conditions on granules and tablet properties

Abstract

Dry granulation is an agglomeration process used to produce size-enlarged particles (granules), improving the handling properties of powders such as flowability. In this process, powders are compacted using a roll press to produce ribbons, which are milled in granules used further in the tableting process. The granule and tablet properties are influenced by the existence of different designs of the roll compactors, milling systems and the interaction between process parameters and raw material properties. The main objective of this work was to investigate how different roll-compaction conditions and milling process parameters impact on ribbons, granules and tablet properties, highlighting the role of the sealing system (cheek plates and rimmed roll). In this context, two common excipients differing in their mechanical behaviour (MCC and mannitol) are used. The study is based on the analysis of granule size distribution together with the characterization of loss of compactability during die compaction. Results show that the tensile strength of tablets is lower when using granules than when the raw materials are compressed. Moreover, the plastic material (MCC) is more sensitive than the brittle one (mannitol). Regarding the roll-force, it is observed that the higher the roll force, the lower the tensile strength of tablets from granulated material is. These findings are in agreement with the literature. The comparison of sealing systems shows that the rimmed-roll system leads to slightly stronger tablets than the use of cheek plates. In addition, the use of the rimmed-roll system reduces the amount of fines, in particular when high roll force is applied. Overall, it can be concluded that roll-compaction effect is predominant over the milling effect on the production of fines but less significant on the tablet properties. This study points out that the balance between a good flowability by reducing the amount of fines and appropriate tablet strength is achieved with rimmed-roll and the highest roll-force used.

RTD-based material tracking in a fully-continuous dry granulation tableting line

“…Although the machinery and basic principles of roller compaction have been used for decades, recent advances in the machine design allow a better control of the ribbon density. Also, there now exists an improved understanding of the effects that process parameters and material characteristics have on the ribbon density, variability, granule properties and the final dosage forms (i.e., tablets) (Heiman et al, 2015;Mazor et al, 2017;Orefice and Khinast, 2017;Perez-Gandarillas et al, 2016, 2015Pérez Gago and Kleinebudde, 2017;Souihi et al, 2015Souihi et al, , 2013. The results suggest that both the process parameters and the material characteristics can affect the ribbon density, the amount of fines after granulation and the tablet tensile strength.…”

Model-based approach to the design of pharmaceutical roller-compaction processes

“…By applying a specific compaction force, the material is compressed into a so-called ribbon. It is subsequently milled into granules (6) using various mills and milling parameters, which are known to affect the properties of final granules (Perez-Gandarillas et al, 2016). Ribbon density or solid fraction, defined as the mass of material per volume of ribbon, is commonly considered a critical quality attribute (CQA) of an RC process (Vervaet and Remon, 2005, Fonteyne et al, 2015, Park et al, 2018).…”

Computational intelligence models to predict porosity of tablets using minimum features

“…The data set is explained in Perez-Gandarillas et al23 The validation set is composed of data generated by varying roll compaction over two sets of tooling (cheek plates and sealed rim rolls) and two roll compaction forces (4 kN/cm and 8 kN/cm). The ribbons were milled under constant settings and granules were compacted under seven different die compaction forces (Table 1B).…”