Mechanically promoted lipid-based filaments via composition tuning for extrusion-based 3D-printing.

Lipid excipients are favorable materials in pharmaceutical formulations owing to their natural, biodegradable, low-toxic and solubility/permeability enhancing properties. The application of these materials with advanced manufacturing platforms, particularly filament-based 3D-printing, is attractive for personalized manufacturing of thermolabile drugs. However, the filament's weak mechanical properties limit their full potential. In this study, highly flexible filaments were extruded using PG6-C16P, a lipid-based excipient belonging to the group of polyglycerol esters of fatty acids (PGFAs), based on tuning the ratio between its major and minor composition fractions. Increasing the percentage of the minor fractions in the system was found to enhance the relevant mechanical filament properties by 50-fold, guaranteeing a flawless 3D-printability. Applying a novel liquid feeding approach further improved the mechanical filament properties at lower percentage of minor fractions, whilst circumventing the issues associated with the standard extrusion approach such as low throughput. Upon drug incorporation, the filaments retained high mechanical properties with a controlled drug release pattern. This work demonstrates PG6-C16 P as an advanced lipid-based material and a competitive printing excipient that can empower filament-based 3D-printing.

Filament-based 3D-printing of placebo dosage forms using brittle lipid-based excipients.

In order to expand the limited portfolio of available polymer-based excipients for fabricating three-dimensional (3D) printed pharmaceutical products, Lipid-based excipients (LBEs) have yet to be thoroughly investigated. The technical obstacle of LBEs application is, however their crystalline nature that renders them very brittle and challenging for processing via 3D-printing. In this work, we evaluated the functionality of LBEs for filament-based 3D-printing of oral dosage forms. Polyglycerol partial ester of palmitic acid and polyethylene glycols monostearate were selected as LBEs, based on their chemical structure, possessing polar groups for providing hydrogen-bonding sites. A fundamental understanding of structure-function relationship was built to screen the critical material attributes relevant for both extrusion and 3D-printing processes. The thermal behavior of lipids, including the degree of their supercooling, was the critical attribute for their processing. The extrudability of materials was improved through different feeding approaches, including the common powder feeding and a devised liquid feeding setup. Liquid feeding was found to be more efficient, allowing the production of filaments with high flexibility and improved printability. Filaments with superior performance were produced using polyglycerol ester of palmitic acid. In-house designed modifications of the utilized 3D-printer were essential for a flawless processing of the filaments.