Abstract
3D printing by selective laser sintering (SLS) of high-dose drug delivery systems using pure brittle crystalline active pharmaceutical ingredients (API) is possible but impractical. Currently used pharmaceutical grade excipients, including polymers, are primarily designed for powder compression, ensuring good mechanical properties. Using these excipients for SLS usually leads to poor mechanical properties of printed tablets (printlets). Composite printlets consisting of sintered carbon-stained polyamide (PA12) and metronidazole (Met) were manufactured by SLS to overcome the issue. The printlets were characterized using DSC and IR spectroscopy together with an assessment of mechanical properties. Functional properties of the printlets, i.e., drug release in USP3 and USP4 apparatus together with flotation assessment, were evaluated. The printlets contained 80 to 90% of Met (therapeutic dose ca. 600 mg), had hardness above 40 N (comparable with compressed tablets) and were of good quality with internal porous structure, which assured flotation. The thermal stability of the composite material and the identity of its constituents were confirmed. Elastic PA12 mesh maintained the shape and structure of the printlets during drug dissolution and flotation. Laser speed and the addition of an osmotic agent in low content influenced drug release virtually not changing composition of the printlet; time to release 80% of Met varied from 0.5 to 5 h. Composite printlets consisting of elastic insoluble PA12 mesh filled with high content of crystalline Met were manufactured by 3D SLS printing. Dissolution modification by the addition of an osmotic agent was demonstrated. The study shows the need to define the requirements for excipients dedicated to 3D printing and to search for appropriate materials for this purpose.
Highlights
Formulation A (80/20/0/100) was a basic composition. This formulation was modified to analyze the influence of changes of several factors on the properties of the Floating Drug Delivery Systems (FDDS)
The results presented confirmed together with literature data,ingave the strong
Using pharmaceutical-grade excipients frequently leads to poor mechanical characteristics of the printlets manufactured with selective laser sintering (SLS) technology
Summary
Application of Floating Drug Delivery Systems (FDDS) is the primary method of increasing gastric residence time [1]. FDDS are suitable for the treatment of local creativecommons.org/licenses/by/ 4.0/). Metronidazole (Met) belongs to the group of first choice chemotherapeutics in H. pylori treatment. Its pKa is 2.6 and its solubility in diluted (0.1 mol/L) hydrochloric acid is 2.2 mg/mL [3,4]. The study of Shah et al, 1999 has shown that Met is stable in simulated gastric fluid (SGF, pH 1.2) at 37 ◦ C for 24 h [5]
Published Version (Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have