Twin-screw Melt Granulation as alternative Granulation Strategy

Abstract

Melt granulation is an interesting alternative technique to produce both, immediate and controlled-release final products using twin-screw extruders. The aim of this current work was to gain a deeper understanding of the granule’s characteristic obtained from TSMG and their influence on further processing of these granules into tablets. Therefore, the following topics were investigated in this work: <br /> • The role of binder distribution in the final tablets made of melt granules and their physical mixtures was examined and quantified via image analysis of energy dispersive X-ray maps. The influence of primary particle-size of both filler (non-molten phase) and binder (molten-phase) was systematically evaluated, regarding the compaction and compression performance. The obtained melt granules, where formed either by distribution or immersion mechanism (chapter 3). <br /> • The compression behavior of granules i.e. mechanical characteristics and deformation behavior was precisely analyzed by out-of-die and in-die compression analysis. This increases knowledge of the granule’s compression characteristics and is a helpful tool for quality by design, if special drug product attributes are required. Furthermore, it helps to define the optimal binder content for the formulation (chapter 4). <br /> • Comparison of granules derived from twin-screw melt granulation and HSM process. Relevant critical quality attributes were defined, including particle size distribution, yield (100-710 µm particle size), shape factor, bulk and tapped density as well as the compressibility index, porosity, specific surface area, flowability (mass flow), tabletability and binder distribution. This work aims to ease process adaptions needed, when changing from batch to continuous production (chapter 5). <br /> • The suitability of TSMG to enhance the dissolution of poorly soluble APIs was investigated. Soluplus® and Kolliphor® P407 were chosen as functional melt binders and compared to the hydrophilic binder PEG 6000. Due to their amphiphilic structure, they enhance the wettability and dissolution of the lipophilic model API carbamazepine (chapter 6). <br /> • Super-disintegrants were systematically evaluated to achieve immediate release formulation of the model drug paracetamol. The performance of croscarmellose sodium, crospovidone and sodium starch glycolate was tested intra- and extra-granular, which is a crucial point for continuous processing, as additional mixing steps might be needed in the processing-line (chapter 7).