Abstract
Filaments loaded with griseofulvin (GF), a model poorly water-soluble drug, were prepared and used for 3D printing via fused deposition modeling (FDM). GF was selected due to its high melting temperature, enabling lower temperature hot-melt extrusion (HME) keeping GF largely crystalline in the filaments, which could help mitigate the disadvantages of high HME processing temperatures such as filament quality, important for printability and the adverse effects of GF recrystallization on tablet properties. Novel aspects include single-step fusion-assisted ASDs generation during FDM 3D printing and examining the impact of tablet surface areas (SA) through printing multi-mini and square-pattern perforated tablets to further enhance drug supersaturation during dissolution. Kollicoat protect and hydroxypropyl cellulose were selected due to their low miscibility with GF, necessary to produce crystalline filaments. The drug solid-state was assessed via XRPD, DSC and FT-IR. At 165 °C HME processing temperature, the filaments containing ~80% crystalline GF were printable. Fusion-assisted 3D printing led to GF supersaturation of ~153% for cylindrical tablets and ~293% with the square-pattern perforated tablets, indicating strong monotonous impact of tablet SA. Dissolution kinetics of drug release profiles indicated Fickian transport for tablets with higher SA, demonstrating greater SA-induced drug supersaturation for well-designed 3D printed tablets.
Highlights
Further lowering the temperature detrimentally increased the required torque, which is not recommended for the instrument safety [23,38]
The filaments produced at the temperature in the range of 165–190 ◦ C (H165–H190) were opaque, while those produced at 210 ◦ C (H210) were clearer, implying the formation of the amorphous structure [6]
The proposed methodology of lower hot-melt extrusion (HME) processing temperature to produce filaments containing largely crystalline GF, followed by single-step fusion-assisted amorphous solid dispersions (ASDs) generation during fused deposition modeling (FDM) 3D printing, could achieve GF supersaturation during in vitro dissolution. This strategy significantly minimized the disadvantages of high HME profrom FDM 3D tablets
Summary
One of the most successful and common strategies to address solubility limited bioavailability is the formation of amorphous solid dispersions (ASDs). This approach relies on the dispersion of a drug within hydrophilic carriers leading to an amorphous mixture [4,5,6,7,8,9,10,11,12] that potentially enhances the dissolution rate since kinetic solubility of the amorphous drug is greater than the crystalline counterpart [13,14].
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