New insights into the effects of porosity, pore length, pore shape and pore alignment on drug release from extrusion-based additive manufactured pharmaceuticals  

Bin Zhang, Andy Gleadall, Peter Belton, Thomas McDonagh, Richard Bibb, Sheng Qi

Research output: Contribution to journalReview articlepeer-review

Abstract

Material extrusionbased additive manufacturing (ME-AM) has been recently adopted by the pharmaceutical field as a potential method for decentralised small-batch manufacturing of personalised solid dosage forms. The unique advantage of ME-AM is the ability to implement a wide range of micro-scale internal structures within a dosage form that can be used to manipulate the drug release kinetics. However, currently, there is no fundamental understanding of how the design of microstructures of a dosage form can control drug release. This study used polycaprolactone/ibuprofen as the model system to investigate four key geometric parameters of microstructures, printing pore length (by changing layer number), porosity (by varying the pore width), pore shape (by changing the filament intersection angles from 90° to 30°), and pore alignment, which allowed the construction of a wide range of interior microstructures within a drug-loaded 3D construct. This is the first work to have systematically investigated the interrelated effects of these parameters. The surface area/volume ratio (SA/V) of the constructs were simulated using the newly developed VOLume COnserving model (VOLCO). Four key points were found from this study: (1) drug release rate significantly increased with increasing porosity; (2) pore shape (or filament intersection angles) showed no significant effect on the drug release rate; (3) for the first time, a critical layer number (Lc) or (pore length) effect was observed and reported. The layer number only had a significant impact on drug release when below Lc; (4) when pore width was small, pore alignment significantly affected the release kinetics. The outcomes of this study provide clear principles and design guidance on using microstructures to control drug release from ME-AM solid dosage forms.

Original languageEnglish
Article number102196
JournalAdditive Manufacturing
Volume46
Early online date22 Jul 2021
DOIs
Publication statusPublished - Oct 2021

Keywords

  • Controlled drug release
  • Design for additive manufacturing
  • Geometrical parameters
  • Hot-melt extrusion
  • Microstructure control
  • VOLCO model

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