TY - JOUR

T1 - Solventless amorphization and pelletization using a high shear granulator. Part I; feasibility study using indomethacin

AU - Kondo, Keita

AU - Rades, Thomas

N1 - Funding Information: We are grateful to ingredientpharm, a brand of Advanced Drug Delivery Technologies Ltd (Pratteln, Switzerland) for supplying us with CELLETS® 127, 175, 200, 350, and 500 for this work. Keita Kondo acknowledges The New Pharmaceutical Technology and Engineering Foundation in Japan (Research Abroad Grant in 2019) for financial support. Funding Information: We are grateful to ingredientpharm, a brand of Advanced Drug Delivery Technologies Ltd (Pratteln, Switzerland) for supplying us with CELLETS® 127, 175, 200, 350, and 500 for this work. Keita Kondo acknowledges The New Pharmaceutical Technology and Engineering Foundation in Japan (Research Abroad Grant in 2019) for financial support.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Amorphous drug-layered pellets

KW - Drug pelletization

KW - High shear granulator

KW - Indomethacin

KW - Microcrystalline cellulose spheres

KW - Solventless amorphization

U2 - 10.1016/j.ejpb.2022.11.010

DO - 10.1016/j.ejpb.2022.11.010

M3 - Journal article

C2 - 36400256

AN - SCOPUS:85142174519

VL - 181

SP - 147

EP - 158

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -