Direct Powder Extrusion 3D Printing of Praziquantel to Overcome Neglected Disease Formulation Challenges in Paediatric Populations

Abstract

For the last 40 years, praziquantel has been the standard treatment for schistosomiasis, a neglected parasitic disease affecting more than 250 million people worldwide. However, there is no suitable paediatric formulation on the market, leading to off-label use and the splitting of commercial tablets for adults. In this study, we use a recently available technology, direct powder extrusion (DPE) three-dimensional printing (3DP), to prepare paediatric Printlets™ (3D printed tablets) of amorphous solid dispersions of praziquantel with Kollidon® VA 64 and surfactants (Span™ 20 or Kolliphor® SLS). Printlets were successfully printed from both pellets and powders obtained from extrudates by hot melt extrusion (HME). In vitro dissolution studies showed a greater than four-fold increase in praziquantel release, due to the formation of amorphous solid dispersions. In vitro palatability data indicated that the printlets were in the range of praziquantel tolerability, highlighting the taste masking capabilities of this technology without the need for additional taste masking excipients. This work has demonstrated the possibility of 3D printing tablets using pellets or powder forms obtained by HME, avoiding the use of filaments in fused deposition modelling 3DP. Moreover, the main formulation hurdles of praziquantel, such as low drug solubility, inadequate taste, and high and variable dose requirements, can be overcome using this technology.

Quality of FDM 3D Printed Medicines for Pediatrics: Considerations for Formulation Development, Filament Extrusion, Printing Process and Printer Design

“…Entrapping by the printed polymers may be sufficient for taste masking of bitter compounds [30,31]. (c) High viscosity hydrophilic polymers may prevent fast hydration and dissolution of the dosage form, thereby reducing the migration to the taste receptors on the tongue and the resulting taste sensation.…”

3D Printing of Pediatric Medication: The End of Bad Tasting Oral Liquids?—A Scoping Review

“…The concentration after 10 min of testing should not exceed the bitterness threshold concentration for successful taste-masking. Both studies concluded their formulations were sufficiently taste-masking [42,49]. Furthermore, when comparing the dissolution of the 3D-printed tablets in artificial saliva to tablets produced with direct compression, the directly compressed tablets fully released the drug in 50 s. This indicated no tastemasking of the directly compressed tablets [42].…”

“…Dose flexibility has also been achieved by altering the drug concentration in the tablet matrix [39,49], though a higher drug concentration could reduce the printability of the tablet matrix [49]. For inkjet printing and drop-on-solid 3D printing, the concentration of the drug in the printing ink can be altered to adjust to printed dose [52,55,56].…”

“…Finally, heated extrusion-based 3D printers can enhance solubility properties of poorly soluble drugs. In one study, hot-melt extrusion (HME) followed by DPE 3D printing was used to enhance the drug release of 100 and 150 mg praziquantel printed tablets after 2 h by more than four-fold as compared to pure praziquantel [49]. Similarly, another study improved the dissolution of rufinamide.…”

“…One study then used these filaments, which contained the bitter model drug caffeine, directly in an FDM 3D printer to produce donut-shaped tablets [42]. In the other study, the praziquantel containing filaments were further processed prior to use in a DPE 3D printer [49]. The effectiveness of the tastemasking was tested by performing adjusted in vitro dissolution testing using simulated saliva fluid.…”