Levofloxacin implants with predefined microstructure fabricated by three-dimensional printing technique

Abstract

A novel three-dimensional (3D) printing technique was utilized in the preparation of drug implants that can be designed to have complex drug release profiles. The method we describe is based on a lactic acid polymer matrix with a predefined microstructure that is amenable to rapid prototyping and fabrication. We describe how the process parameters, especially selection of the binder, were optimized. Implants containing levofloxacin (LVFX) with predefined microstructures using an optimized binder solution of ethanol and acetone (20:80, v/v) were prepared by a 3D printing process that achieved a bi-modal profile displaying both pulsatile and steady state LVFX release from a single implant. The pulse release appeared from day 5 to 25, followed by a steady state phase of 25 days. The next pulse release phase then began at the 50th day and ended at the 80th day. To evaluate the drug implants structurally and analytically, the microscopic morphologies and the in vitro release profiles of the implants fabricated by both the 3D printing technique and the conventional lost mold technique were assessed using environmental scanning electron microscopy (ESEM) and UV absorbance spectrophotometry. The results demonstrate that the 3D printing technology can be used to fabricate drug implants with sophisticated micro- and macro-architecture in a single device that may be rapidly prototyped and fabricated. We conclude that drug implants with predefined microstructure fabricated by 3D printing techniques can have clear advantages compared to implants fabricated by conventional compressing methods.