TY - JOUR

T1 - Wet granulation of co-amorphous indomethacin systems

AU - Schütz, David

AU - Timmerhaus, Annika

AU - Grohganz, Holger

N1 - Funding Information: The authors wish to thank Rikke Helstrup and Kilian Stuhler for providing raw data for one week of stability testing and the sieving analysis of three granule batches, respectively. Chemical structures were created via BIOVIA Draw 2019. Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

N2 - The feasibility of co-amorphous systems to be wet granulated together with microcrystalline cellulose (MCC) was investigated. Solid state and molecular interactions were analysed for various co-amorphous drug-amino acid formulations of indomethacin with tryptophan and arginine, respectively, via XRPD, DSC and FTIR. The co-amorphous binary systems were produced by ball-milling for 90 min at different molar ratios followed by wet granulation with MCC and water in a miniaturised scale. Tryptophan containing systems showed crystalline reflections in their XRPD diffractograms and endothermal events in their DSC analyses, and were therefore excluded from upscaling attempts. The systems containing arginine were found to be remain amorphous for at least ten months and were upscaled for production in a high-shear blender under application of two different parameter settings. Under the harsher instrument settings, a composition with a low MCC ratio experienced recrystallisation during wet granulation, while all other compositions could be successfully processed via wet granulation and stayed stable for a storage period of at least twelve weeks, indicating that wet granulation of co-amorphous systems can be feasible.

AB - The feasibility of co-amorphous systems to be wet granulated together with microcrystalline cellulose (MCC) was investigated. Solid state and molecular interactions were analysed for various co-amorphous drug-amino acid formulations of indomethacin with tryptophan and arginine, respectively, via XRPD, DSC and FTIR. The co-amorphous binary systems were produced by ball-milling for 90 min at different molar ratios followed by wet granulation with MCC and water in a miniaturised scale. Tryptophan containing systems showed crystalline reflections in their XRPD diffractograms and endothermal events in their DSC analyses, and were therefore excluded from upscaling attempts. The systems containing arginine were found to be remain amorphous for at least ten months and were upscaled for production in a high-shear blender under application of two different parameter settings. Under the harsher instrument settings, a composition with a low MCC ratio experienced recrystallisation during wet granulation, while all other compositions could be successfully processed via wet granulation and stayed stable for a storage period of at least twelve weeks, indicating that wet granulation of co-amorphous systems can be feasible.

KW - Amino acid

KW - Co-amorphous

KW - Downstream processing

KW - Molecular interactions

KW - Solid state

KW - Wet granulation

U2 - 10.1016/j.ijpharm.2023.123318

DO - 10.1016/j.ijpharm.2023.123318

M3 - Journal article

C2 - 37586574

AN - SCOPUS:85168133442

VL - 644

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 123318

ER -