Twin-screw melt granulation with PEG 8000: Effect of binder particle size and processing temperature on the granule and tablet properties

Twin-screw melt granulation (TSMG) is one of the promising green technological approaches for the manufacturing of solid dosage forms of pharmaceuticals and nutraceuticals. PEG 8000 is one of the most popular TSMG binders. The effect of different low-melting grades of PEG on the TSMG granules’ properties is described in the literature, however, not enough attention was paid to their effect on the mechanical properties of tablets. The aim of this study was to investigate the effect of PEG 8000 particle size and twin-screw melt granulation temperature on the properties of resultant MCC-CaHPO₄ granulated powder and tablets.

Highlights

• Granules’ and tablets’ properties as a function of PEG 8000 particle size and twin-screw melt granulation temperature were investigated.
• Both factors influenced granules and tablet structure and their properties.
• Structure-mechanical properties relationship was elucidated.

The effect of melt granulation temperature was investigated with a medium PEG 8000 fraction (200–400 µm). While the effect of melt granulation temperature was explored at 115, 135, and 155 °C, the effect of PEG 8000 particle size was investigated using small, medium, and big fractions (0–200, 200–400, and 400–500 µm, respectively) at 135 °C. The granules were investigated by microscopic methods and were characterised in terms of flowability, angle of repose, particle size distribution, bulk and tapped density. Tablets were prepared with a compaction simulator. The analysis of the tablets provided their respective in-die Heckel plots, plastic energy and elastic energy profiles, as well as tabletability, compressibility, and compactability. The microscopic methods reveal the effect of PEG 8000 particle size on the granule and tablet structure, as well as assume the effect of granulation temperature. These insights were used to explain the differences between the mechanical properties of the tablets that were prepared using different PEG 8000 particle size fractions and at various melt granulation temperature. Despite the improved powder rheology, the tablets prepared with the PEG 8000 formulation via melt granulation have shown higher plasticity and lower tensile strength compared to ungranulated directly compressed MCC-CaHPO₄.

Materials

Microcrystalline cellulose (MCC) powder (Ceolus™ UF-711; Asahi Kasei, Japan) and dicalcium phosphate anhydrous (CaHPO₄; DI-CAFOS® A60; Budenheim KG, Germany) were used as primary components, polyethylene glycol with average molecular weight 7000–9000 g/mol (PEG 8000; Kollisolv® PEG 8000; BASF SE, Germany) was used as binder in melt granulation process and lubricant for tableting of granulated formulations; while silica dioxide (SYLOID® 244FP; Grace GmbH, Germany) and sodium stearyl fumarate  (Pruv, JRS Pharma).

Read more

Zoltán Márk Horváth, Liga Petersone, Valentyn Mohylyuk, Twin-screw melt granulation with PEG 8000: Effect of binder particle size and processing temperature on the granule and tablet properties, Advanced Powder Technology, Volume 35, Issue 9, 2024, 104585, ISSN 0921-8831, https://doi.org/10.1016/j.apt.2024.104585.

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