Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments

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.

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2.1. Materials

Griseofulvin (GF; Letco Medical, Decatur, AL, USA) was used as the model Biopharmaceutics Classification System (BCS) class II drug. GF is a crystalline drug with a melting point (T_m) of 220 °C [54]. It is considered a challenging drug for the development of ASDs given the fact that it rapidly crystallizes [46]. Hydroxypropyl cellulose (HPC, SL grade, Nisso America Inc., New York, NY, USA) is a semi-crystalline polymer with the glass transition temperature (T_g) of in range −25–0 °C and T_m of around 170–200 °C [42,54]. It has been reported as a suitable polymer for FDM 3D printing [26,55,56] due to its ability to produce filaments with satisfactory mechanical properties. In addition, it helps enhance the wettability of hydrophobic GF particles [57]. Kollicoat^® Protect (KP, BASF, Tarrytown, NY, USA) is readily soluble in water and composed of polyvinyl alcohol-polyethylene glycol graft copolymer, polyvinyl alcohol and fumed silica. It has a T_m of 205 °C and a T_g of 45 °C and is known to improve protection against moisture [58]. Further, Kollicoat^® Protect lowers the surface tension of water i.e., surface tension is 61.6 mN/m for 0% solution and 42.3 mN/m for 15% solution [58]. An aqueous solution of sodium dodecyl sulfate (SDS) (Sigma-Aldrich, Saint Louis, MO, USA) was used as a solvent at 7.2 g/L concentration for assay testing.

Buyukgoz, G.G.; Kossor, C.G.; Davé, R.N. Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments. Pharmaceutics 2021, 13, 1857. https://doi.org/10.3390/pharmaceutics13111857