TY - JOUR

T1 - Solventless amorphization and pelletization using a high shear granulator. Part II; Preparation of co-amorphous mixture-layered pellets using indomethacin and arginine

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® 175 for this work. Keita Kondo acknowledges The New Pharmaceutical Technology and Engineering Foundation in Japan (the Research Abroad Grant in 2019) for financial support.

PY - 2022

Y1 - 2022

N2 - The aim of this study was to investigate the preparation of co-amorphous mixture-layered pellets using solventless pelletization and amorphization using a high shear granulator (as suggested in the first part of this study) by high shear mixing of drug crystals and a crystalline co-former with inactive spheres. Mixtures of crystalline indomethacin and arginine at various molar ratios were mixed with microcrystalline cellulose spheres at a weight ratio of 1:10 using the granulator and the resulting particles were characterized using solid-state and particle analytical techniques as well as dissolution testing and physical stability. At jacket temperatures of 20 °C or more of the granulator, co-processing of indomethacin and arginine enhanced amorphization of indomethacin and provided a co-amorphous mixture due to homogenous mixing of indomethacin and arginine amorphous phases. The co-amorphous mixture was deposited on the surface of the spheres, yielding co-amorphous mixture-layered pellets. The co-amorphous mixtures at molar ratios of indomethacin to arginine of 2:1 and 1:1, deposited on the pellets, did not recrystallize for at least 4 weeks. The pellets exhibited higher dissolution characteristics as additional hypromellose could prevent precipitation. These findings demonstrate the potential of this technique as a solventless approach to prepare co-amorphous mixture-layered pellets through a one-step process.

AB - The aim of this study was to investigate the preparation of co-amorphous mixture-layered pellets using solventless pelletization and amorphization using a high shear granulator (as suggested in the first part of this study) by high shear mixing of drug crystals and a crystalline co-former with inactive spheres. Mixtures of crystalline indomethacin and arginine at various molar ratios were mixed with microcrystalline cellulose spheres at a weight ratio of 1:10 using the granulator and the resulting particles were characterized using solid-state and particle analytical techniques as well as dissolution testing and physical stability. At jacket temperatures of 20 °C or more of the granulator, co-processing of indomethacin and arginine enhanced amorphization of indomethacin and provided a co-amorphous mixture due to homogenous mixing of indomethacin and arginine amorphous phases. The co-amorphous mixture was deposited on the surface of the spheres, yielding co-amorphous mixture-layered pellets. The co-amorphous mixtures at molar ratios of indomethacin to arginine of 2:1 and 1:1, deposited on the pellets, did not recrystallize for at least 4 weeks. The pellets exhibited higher dissolution characteristics as additional hypromellose could prevent precipitation. These findings demonstrate the potential of this technique as a solventless approach to prepare co-amorphous mixture-layered pellets through a one-step process.

KW - Arginine

KW - Co-amorphous mixture layered pellets

KW - Drug pelletization

KW - High shear granulator

KW - Indomethacin

KW - Microcrystalline cellulose spheres

KW - Solventless amorphization

U2 - 10.1016/j.ejpb.2022.11.011

DO - 10.1016/j.ejpb.2022.11.011

M3 - Journal article

C2 - 36400253

AN - SCOPUS:85142313670

VL - 181

SP - 183

EP - 194

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -