Tailoring the release of highly loaded amorphous solid dispersions via additive manufacturing

Abstract

In the last decades, tremendous improvements have been made in enhancing the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Lately, their customisation potential has become a reality through filament-based 3D-printing (3DP). Highly loaded oral amorphous solid dispersions (ASDs) are of particular interest, since they drastically reduce the pill burden. However, such systems are limited by their high tendency of API recrystallisation, compromising the API solubility and the mechanical properties of filaments fabricated for 3DP. The following work closes this gap by developing compact 3DP tablets containing an ASD system of 70 % itraconazole in hydroxypropyl methylcellulose acetate succinate (HPMCAS). The processability via HME and 3DP processes was thoroughly investigated by considering filament properties such as solid-state, rheology and mechanical behaviour. Even after six months of storage, the ASD did not show recrystallisation and maintained a zero-order drug release for variable 3DP infill patterns, demonstrating the potential of this approach for on-demand processing at the point-of-care. A strong differentiation in release kinetics was found for different infills that can be used for further improvement of the product to allow tailored release rates. This work provides a strong basis for successful personalisation of highly loaded ASDs via 3DP.