3D-printed implantable devices with biodegradable rate-controlling membrane for sustained delivery of hydrophobic drugs

Abstract

Implantable drug delivery systems offer an alternative for the treatments of long-term conditions (i.e. schizophrenia, HIV, or Parkinson’s disease among many others). The objective of the present work was to formulate implantable devices loaded with the model hydrophobic drug olanzapine (OLZ) using robocasting 3D-printing combined with a pre-formed rate controlling membrane. OLZ was selected as a model molecule due to its hydrophobic nature and because is a good example of a molecule used to treat a chronic condition schizophrenia. The resulting implants consisted of a poly(ethylene oxide) (PEO) implant coated with a poly(caprolactone) (PCL)-based membrane. The implants were loaded with 50 and 80% (w/w) of OLZ. They were prepared using an extrusion-based 3D-printer from aqueous pastes containing 36–38% (w/w) of water. The printing process was carried out at room temperature. The resulting implants were characterized by using infrared spectroscopy, scanning electron microscopy, thermal analysis, and X-ray diffraction. Crystals of OLZ were present in the implant after the printing process. In vitro release studies showed that implants containing 50% and 80% (w/w) of OLZ were capable of providing drug release for up to 190 days. On the other hand, implants containing 80% (w/w) of OLZ presented a slower release kinetics. After 190 days, total drug release was ca. 77% and ca. 64% for implants containing 50% and 80% (w/w) of OLZ, respectively. The higher PEO content within implants containing 50% (w/w) of OLZ allows a faster release as this polymer acts as a co-solvent of the drug.

Development of 3D-printed subcutaneous implants using concentrated polymer/drug solutions

“…OLZ was quantified using reverse-phase high-performance liquid chromatography (RP-HPLC) (Agilent 1100 series system, Agilent Technologies UK ltd., Stockport, UK) as reported previously (Picco et al, 2022). The column used to achieve separation was a Waters X-Select CSH C18 (3.5 µm pore size, 3.0 × 150 mm) (Agilent Technologies UK ltd., Stockport, UK).…”

The Quest for Child-Friendly Carrier Materials Used in the 3D Semi-Solid Extrusion Printing of Medicines

“…Syringe-based 3D printing and piston-based extrusion. Drug/PEO ratio (50/50 and 80/20) at 60 °C and 80 °C [ 36 ]…”

“…For two of the tested materials, it was impossible to create a semi-solid mixture by DAC either the mixture became too viscous (PEO) or too solid (Eudragit ® ). Picco et al successfully mixed their formulation of PEO with olanzapine by using DAC, but they dissolved PEO in water to mix [ 36 ]. Eudragit ® was successfully printed by Kuźmińska et al, but they lowered the viscosity of their formulation by adding plasticizers such as triethyl citrate.…”

Fabrication and Characterisation of 3D-Printed Triamcinolone Acetonide-Loaded Polycaprolactone-Based Ocular Implants

“…However, most of the drug delivery systems above involve using organic solvents during their fabrication processes, which might cause side effects, such as irritation, if they remain in the implant. In addition, PCL also has been used in implantable devices for sustained delivery of different drugs such as antibiotics [ 28 ], antipsychotic drugs [ 29 , 30 ]; antiplatelet agents, i.e., dipyridamole and acetylsalicylic acid [ 31 , 32 , 33 ]; non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen [ 34 ]; or even thyroid hormones such levothyroxine [ 34 ]. PCL has been shown to be well-tolerated in eyes and does not cause noticeable inflammation because it does not produce any acidic products of biodegradation [ 26 ].…”