Exploration and Preparation of a Dose-Flexible Regulation System for Levetiracetam Tablets via Novel Semi-Solid Extrusion Three-Dimensional Printing

J Pharm Sci. 2019 Feb;108(2):977-986. doi: 10.1016/j.xphs.2018.10.001. Epub 2018 Oct 10.

Abstract

Levetiracetam therapy is often associated with high levels of individual variation in the recommended dose required to achieve preferential treatment. Thus, a reliable and dynamic regulation system to accurately tailor dose is necessary. The main objective of this study is to explore and prepare a dose-flexible control system suitable for rapid release tablets equipped with high drug loading and a cylindrical model design. Semi-solid extrusion 3-dimensional printing was utilized to fabricate a series of tablets of increased volume. This method was compatible with 3 patterns to regulate the volumes to manipulate the tablet mass and achieve tailored personalized precision dosing. All tablets from each pattern exhibited a smooth surface and regular shape, as well as sufficient mechanical strength. A good linear correlation between the mass and theoretical volume of the tablets was maintained, regardless of the pattern used. The range of dose accuracy was between 103.3% and 96.2%, with an acceptable variation coefficient in the range of 0.6%-3.2%. Faster release behavior for levetiracetam can be achieved from the small-sized tablets due to their larger surface area/mass ratio. All the results demonstrated the potential and capability of semi-solid extrusion 3-dimensional printing as a novel pharmaceutical manufacturing technique to provide a dynamic and highly accurate controllable system for preparing patient-tailored medicines.

Keywords: dissolution behavior; dose-flexible regulation system; individual-tailored medicines; levetiracetam; linear correlation; mechanical properties; patterns; semi-solid extrusion 3D printing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / administration & dosage
  • Anticonvulsants / chemistry*
  • Drug Compounding / instrumentation*
  • Drug Liberation
  • Levetiracetam / administration & dosage
  • Levetiracetam / chemistry*
  • Printing, Three-Dimensional*
  • Solubility
  • Tablets
  • Tensile Strength

Substances

  • Anticonvulsants
  • Tablets
  • Levetiracetam