Tablets are the most common solid dosage forms. In order to decrease variability in tablet quality many formulations are granulated prior to tableting. Compared to common continuous granulation methods, hot-melt extrusion (HME) offers the possibility to enhance or adapt certain physicochemical characteristics of the active pharmaceutical ingredient (API) . This is achieved by the formation of amorphous dispersions or solid solution of the API in a polymeric carrier. Moreover, HME has the advantage of continuous processes, such as good process stability, permanent process control, small footprint and decreased manufacturing time.
Our aim is to develop a continuous process line for the production of immediate release tablets (85% API released within 30 min) for a poorly soluble API (BCS II). The line consists of (1) a hot-melt extruder, (2) a die-face pelletizer, (3) a continuous blender and (4) a tableting machine making tablets in a continuous way. The API solubility is increased by formation of an amorphous system via HME. A die-face pelletizer is used to directly produce almost spherical pellets for subsequent tableting.
Formulation screening was performed to select the most promising carrier substances to match the desired release profile and stability. Based on literature research and experience five promising carriers were selected for the screening. Melt rheology measurements were performed to estimate processability and thermal sensitivity. Additionally, table top extrusions (D=9 mm, L/D=20) were carried out to study the solid state after exposure to shear forces during extrusion. Based on this screening the best formulation was selected for HME runs (D=18 mm L/D=40) on technical lab scale. The extrusion setup was designed based on material information gathered during formulation screening. The temperature profile was selected based on the DSC and rheology data. Finally, the formulation was characterized regarding the mechanical behavior and surface properties.
Pure pellets and mixtures of tablets with compaction aids were subsequently tableted using a compaction simulator. Then the tablets were analyzed and compared to the target properties.
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