The Application of 3D Printing in the Formulation of Multilayered Fast Dissolving Oral Films

J Pharm Sci. 2018 Apr;107(4):1076-1085. doi: 10.1016/j.xphs.2017.11.019. Epub 2017 Dec 6.

Abstract

Fast-dissolving oral films (FDFs) provide an alternative approach to increase consumer acceptance by advantage of rapid dissolution and administration without water. Usually, FDFs require taste-masking agents. However, inclusion of these excipients could make developing the formulation a challenging task. Hence, this work employed fused-deposition modeling three-dimensional printing to produce single-layered FDFs (SLFDFs), or multilayered FDFs (MLFDFs) films, with taste-masking layers being separated from drug layer. Filaments were prepared containing polyethylene oxide (PEO) with ibuprofen or paracetamol as model drugs at 60°C. Also, filaments were produced containing polyvinyl alcohol and paracetamol at 130°C. Furthermore, a filament was prepared containing PEO and strawberry powder for taste-masking layer. FDFs were printed at temperatures of 165°C (PEO) or 190°C (polyvinyl alcohol) with plain or mesh designs. High-performance liquid chromatography and mass spectroscopy analysis indicated active ingredient stability during film preparation process. SLFDFs had thicknesses as small as 197 ± 21 μm, and MLFDFs had thicknesses starting from 298 ± 15 μm. Depending on the formulation and design, mesh SLFDFs presented disintegration time as short as 42 ± 7 s, and this was 48 ± 5 s for mesh MLFDFs. SLFDFs showed drug content uniformity in the range of 106.0%-112.4%. In conclusion, this study provides proof-of-concept for the manufacturing of FDFs by using 3D printing.

Keywords: FTIR; LC-MS; calorimetry (DSC); content uniformity; dissolution; drug delivery systems; excipients; formulation; mechanical properties; oral drug delivery.

MeSH terms

  • Acetaminophen / chemistry*
  • Administration, Oral
  • Chemistry, Pharmaceutical / methods
  • Excipients / chemistry
  • Flavoring Agents / chemistry
  • Ibuprofen / chemistry*
  • Polyethylene Glycols / chemistry
  • Polyvinyl Alcohol / chemistry
  • Printing, Three-Dimensional
  • Solubility
  • Technology, Pharmaceutical / methods
  • Temperature

Substances

  • Excipients
  • Flavoring Agents
  • Acetaminophen
  • Polyethylene Glycols
  • Polyvinyl Alcohol
  • Ibuprofen