(51a) The Compression and Compaction Behaviour of Pharmaceutical Powders and Their Binary Mixtures

Powder compaction is a very important production process in the pharmaceutical industry due to the prevalence of tablets as solid dosage form. Therefore, various scientific investigations focused on the investigation of the powder compaction process in the past decades. Nevertheless, the physical processes at particle level during powder compression are still not fully understood and this is the reason for the mainly empirical formulation and process development. The missing process understanding can be attributed to the complexity of the powder compaction process due to the high number of influencing parameters on the one hand and different acting micro-processes on the other hand. Exemplary influencing parameters are particle size distribution, particle shape and deformation behaviour of the raw materials as well as compaction stress and velocity [1; 2]. All these parameters affect the contact area and the number of contacts between the particles and hence, the mechanical and structural properties of the tablets.

Furthermore, it is well known that different micro-processes occur during powder compaction [3–6]. At the beginning of the powder compaction and thus, at low compression stresses, particle rearrangement is the main deformation mechanism and causes the reduction of inter-particulate pores due to the filling of large pores. The increase of compaction stress leads to the elastic and plastic deformation as well as fragmentation of single particles, which, in addition influences the contact area and the number of contacts between the particles. Additionally, elastic deformation of the molecule lattice occurs and causes the decrease of solids volume and thus, an increase of solids density with rising compression stress [7–9]. This phenomenon is referred to as solids compressibility. The different deformation mechanisms do not appear successively, but appear in parallel. The proportions of the single mechanisms differ in dependence on the used materials and process parameters and a differentiation between the mechanisms during the process is difficult or rather impossible. At the decompression phase, elastic recovery of the particles takes place and can lead to the destruction of weak inter-particulate bonds and to the occurrence of capping and lamination phenomena [6; 10; 11].

The missing physical process understanding requires the comprehensive characterization of the compressibility and compactibility of raw materials and the derivation of characteristic material parameters enables a more valid prediction of formulation and process development. The compressibility of a powder can be described by the relation between volume or porosity decrease and compaction stress [4]. Instrumented tablet presses enable the determination of this relationship directly during the compaction process (in-die). Various mathematical models for the description of this relation were developed, such as the models of Heckel, of Kawakita and of Cooper and Eaton [12–14]. Nonetheless, these models are mostly empirical and often describe only one part of the compaction process. Additionally, the existing mathematical models do not consider the phenomenon of solids compressibility.

In this work, the compressibility and compactibility of pharmaceutical powders with different deformation behaviour were investigated using in and out-die analysis. The compaction experiments were performed using the compaction simulator Styl’One Evolution (Medel’Pharm, France), which is a single station tablet press instrumented with force and displacement sensors. Furthermore, the compression and compaction behaviour of binary powder mixtures, consisting of an active pharmaceutical ingredient (API) and an excipient, were investigated under systematic variation of the API concentration. Additionally, a new process function for the description of the in-die compression curves was developed based on mechanistic considerations and their applicability for pharmaceutical powders with different deformation behaviour as well as for binary powder mixtures, was examined. It is found that the new process function is applicable for all model materials and well suited for the derivation of characteristic material parameters. The characteristic material parameters can facilitate formulation and process development.

References

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