Gleadall_Manuscript Revised.pdf (7.59 MB)
New insights into the effects of porosity, pore length, pore shape and pore alignment on drug release from extrusion-based additive manufactured pharmaceuticals
journal contribution
posted on 2021-08-06, 08:57 authored by Bin Zhang, Andy GleadallAndy Gleadall, Peter Belton, Thomas Mcdonagh, Richard Bibb, Sheng QiMaterial extrusion-based 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 release kinetics of the drug. 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.
Funding
Enabling Innovation: Research to Application (EIRA), a Research England Connecting Capability Fund (CCF) project
Redistributed Manufacturing in Deployed Medical Care Network Plus. EP/T014970/1
History
School
- Mechanical, Electrical and Manufacturing Engineering
- Design and Creative Arts
Department
- Design
Published in
Additive ManufacturingVolume
46Publisher
Elsevier BVVersion
- AM (Accepted Manuscript)
Rights holder
© ElsevierPublisher statement
This paper was accepted for publication in the journal Additive Manufacturing and the definitive published version is available at https://doi.org/10.1016/j.addma.2021.102196Acceptance date
2021-07-15Publication date
2021-07-22Copyright date
2021ISSN
2214-7810eISSN
2214-8604Publisher version
Language
- en
Depositor
Dr Andy Gleadall. Deposit date: 3 August 2021Article number
102196Usage metrics
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