University of Sussex
Browse

3D printing in controlled release oral formulations: a comparison to conventional manufacturing methods

Download (7.59 MB)
thesis
posted on 2024-03-25, 13:39 authored by Nour Nashed

In this thesis, fused deposition modelling (FDM), one of the extrusion-based 3D printing technologies, was studied. The impact of FDM, as a manufacturing method, on tablets’ density, porosity, hardness and thus the release of theophylline was investigated in comparison to other conventional manufacturing methods, physical mixture (PM), and hot melt extrusion (HME). The focus was on controlled release formulations, thus, hydrophilic and hydrophobic polymers with slow-release behavior were selected to make the studied formulations. The impact of formulation and manufacturing method on tablets’ robustness to dissolution variables was also studied under many dissolution conditions mimicking fed and fast state in gastrointestinal (GI) tract. On the other hand, the effect of FDM on the stability of polymer molecular weight (Mw) and thus, theophylline release% was inspected compared to other manufacturing methods, PM and HME.

In FDM, high temperatures are applied to produce tablets starting from filaments produced by HME, which is also a thermal process, meaning that FDM printlets undergo dual thermal processes. Thus, and since very few studies have addressed this issue, it was interesting to investigate how this dual thermal process can impact the hardness, true density and porosity of printed tablets and their impact on drug release. Studied formulations were made of thermally stable polymers, hydroxypropyl cellulose (HPC) and ethyl cellulose (EC), and theophylline as a drug. Data showed that printed tablets had the highest hardness (>300N), highest porosity (~20%) and lowest true density compared to PM and HME tablets made of same formulation. Interestingly, printed tablets, though being very hard, showed faster drug release than tablets made by PM and HME which was attributed to both increased porosity and decreased true density after fast heating and cooling process.

The effect of fed and fast conditions on drug release from tablets made via PM, HME and FDM methods was also investigated using a bio-dissolution tester. Dissolution studies showed that FDM printing method resulted in more robust


tablets to different dipping rate and ionic strengths compared to those made by HME and PM methods. This robustness means that printed tablets can give a consistent release behavior when delivered to patients regardless of the contents of GI tract. This robustness of printed tablets to dissolution variables was increased when hydrophobic polymers like EC is used by 35% in the formulation.

The possibility of printing tablets using thermolabile polymer polyethylene oxide (PEO) with high Mw (7M Da and 0.9M Da) was investigated. Data showed that PEO undergoes a reduction in its Mw when processed by printing method, resulting in a faster drug release in printed tablets compared to PM ones. This reduction in Mw was noticeably reversed by adding vitamin E by 5% to the formulation. Findings show that it is possible to get printed tablets with equivalent release profile to PM ones when PEO is used by 10% and vitamin E added by 5%.

History

File Version

  • Published version

Pages

228

Department affiliated with

  • Chemistry Theses

Qualification level

  • doctoral

Qualification name

  • phd

Language

  • eng

Institution

University of Sussex

Full text available

  • Yes

Supervisor

Professor Ali Nokhodchi

Usage metrics

    University of Sussex (Theses)

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC