Solventless amorphization and pelletization using a high shear granulator. Part I; feasibility study using indomethacin
The aim of the current study was to investigate the feasibility of solventless amorphization and pelletization using a high shear granulator, to produce amorphous drug-layered pellets by simply mixing drug crystals and inactive spheres without using solvent and heating. Indomethacin crystals were mixed with microcrystalline cellulose spheres at a weight ratio of 1:10 using the granulator and the resulting particles were then characterized using solid-state and particle analytical techniques as well as pharmaceutically relevant tests. Amorphization of indomethacin crystals progressed with increasing processing time and decreasing jacket temperature. The amorphization rate increased as the spheres became larger and full amorphization was achieved using spheres of 414 and 649 μm in diameter. Indomethacin crystals were pulverized due to mechanical activation by the spheres and the resulting amorphous microparticles were then deposited on the spheres, yielding pellets with an amorphous layer. The pellets exhibited supersaturation characteristics and the dissolution rate was faster than that of quench-cooled indomethacin powder. However, the amorphous drug deposited on the pellets exhibited a lower physical stability than quench-cooled amorphous indomethacin, but recrystallization could be inhibited by co-processing with polyvinylpyrrolidone K-25 stabilizing the amorphous form. The findings suggest the feasibility of the solventless amorphization and pelletization technique.
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The polymorphic γ-form of crystalline indomethacin (IND) (Hangzhou Dayangchem Co. Ltd., Hangzhou, China) was used as the model drug. IND crystals were sieved with a 170-mesh screen (opening: 90 μm) and the powder that passed through the screen was used in the experiments. Microcrystalline cellulose (MCC) spheres (CELLETS® 127, 175, Cellets 200, Cellets 350, and Cellets 500, Advanced Drug Delivery Technologies Ltd, Pratteln, Switzerland) were used as carrier particles.
Keita Kondo, Thomas Rades, Solventless amorphization and pelletization using a high shear granulator. Part I; feasibility study using indomethacin, European Journal of Pharmaceutics and Biopharmaceutics, Volume 181, 2022,
Pages 147-158, ISSN 0939-6411,