2020 EJRNL PP Timothy Pas -1.pdf
Terbatas Irwan Sofiyan
» ITB
Terbatas Irwan Sofiyan
» ITB
In this work, a chemical (and physical) evaluation
of cryogenic milling to manufacture amorphous solid dispersions
(ASDs) is provided to support novel mechanistic insights in the
cryomilling process. Cryogenic milling devices are considered as
reactors in which both physical transitions (reduction in crystallite
size, polymorphic transformations, accumulation of crystallite defects, and partial or complete amorphization) and chemical reactions (chemical decomposition, etc.) can be mechanically triggered. In-depth characterization of active pharmaceutical ingredient (API) (content determination) and polymer (viscosity, molecular weight, dynamic vapor sorption, Fourier transform infrared spectroscopy, dynamic light scattering, and ANS and thioflavin T staining) chemical decomposition demonstrated APIs to be more prone to chemical degradation in case of presence of a polymer. A significant reduction of the polymer chain length was observed and in case of BSA denaturation/aggregation. Hence, mechanochemical activation process(es) for amorphization and ASD manufacturing cannot be regarded as a mild technique, as generally put forward, and one needs to be aware of chemical degradation of both APIs and polymers.