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Quality attributes of lipid tablets produced by semi-solid extrusion 3D printing: Towards personalized dosage forms in a clinical setting
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.ORCID iD: 0000-0002-8917-2612
(English)Manuscript (preprint) (Other academic)
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-500564OAI: oai:DiVA.org:uu-500564DiVA, id: diva2:1751935
Available from: 2023-04-20 Created: 2023-04-20 Last updated: 2023-04-21
In thesis
1. 3D printing of lipid-based formulations into personalized solid oral dosage forms
Open this publication in new window or tab >>3D printing of lipid-based formulations into personalized solid oral dosage forms
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The pharmaceutical development process starts with patient populations and their unmet therapeutic needs. Traditional pharmaceutical manufacturing of solid oral dosage forms is based on the strategy of one-size-fits-all. This is problematic, especially for patient populations with high patient-to-patient variability, as in pediatrics. Historically, pharmaceutical development has focused on the adult population, neglecting the therapeutic needs unique to children. As a result, there is a lack of age-appropriate formulations—available in acceptable dosage forms and suitable dosage strengths—for safe and efficient drug therapies for children. To address this, additive manufacturing, more commonly known as three-dimensional (3D) printing, has emerged as a flexible manufacturing platform for production of dosage forms based on patient needs. 

Interest in 3D printing for pharmaceutical production has grown rapidly; however, to date the research has mainly focused on water-soluble drugs not in need of more advanced drug delivery systems to enable oral absorption. The overall aim of this thesis was therefore to develop lipid-based drug delivery strategies for poorly soluble drugs to be 3D printed into personalized solid oral dosage forms. 

In the first part, an observational study was performed at a pediatric oncology ward, together with analysis of the age-appropriateness of the oral medications. Administration through enteral feeding tubes was identified as the main reason for manipulation of the solid dosage forms. Furthermore, active pharmaceutical ingredients requiring age-appropriate, personalized dosage forms were identified. 

In the next part, emulsion gels from emulsified lipid-based formulations stabilized by surfactants (surfactant-stabilized emulsion gels) or solid particles (Pickering emulsion gel) were developed to incorporate a poorly water-soluble model compound. The rheological properties of the emulsion gels were investigated. The developed emulsion gels were successfully 3D printed into solid oral dosage forms by semi-solid extrusion (SSE). 

In the last part, central quality control attributes, including both the printable formulation and the 3D-printed tablets, were studied in the 3D-printing method developed for one of the emulsion gels. The SSE 3D-printed tablets complied with standardized uniformity tests for both mass and drug content and demonstrated high dose accuracy and short-term storage stability. To conclude, a method for SSE 3D printing of emulsion gels into lipid tablets was developed with promising potential for personalized dosing of lipophilic drugs in a clinical setting.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2023. p. 65
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 334
Keywords
poorly water-soluble drug, lipid-based formulation, Pickering emulsion, emulsion gel, semi-solid extrusion, 3D printing, lipid tablet, personalized dosage form
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Science
Identifiers
urn:nbn:se:uu:diva-500566 (URN)978-91-513-1814-1 (ISBN)
Public defence
2023-06-14, A1:107a, Biomedical Center, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2023-05-23 Created: 2023-04-21 Last updated: 2023-05-24Bibliographically approved

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Johannesson, JennyBergström, Christel

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