Utilising hot melt extrusion and fused deposition modelling based 3D printing technology for the synthesis of solid pharmaceutical dosage forms and innovative drug delivery devices

AlKolaib, Ali (2025). Utilising hot melt extrusion and fused deposition modelling based 3D printing technology for the synthesis of solid pharmaceutical dosage forms and innovative drug delivery devices. University of Birmingham. Ph.D.

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Abstract

Fused deposition modelling (FDM) is a type of three dimensional (3D) printing technology that relies on melt extrusion of thermoplastic materials for the fabrication of objects with virtually limitless opportunities of designs or geometries. Therefore, involving FDM based 3D printing technology in the manufacturing of pharmaceutical dosage forms and medical devices will be a robust method for producing customised pharmaceutical dosage forms and medical devices.

Although there are no commercially available solid dosage forms produced by the FDM based 3D printing technology, the past decade has seen an increasing in research efforts that demonstrated the capacity of FDM based 3D printing to produce pharmaceutical dosage forms with customised release profiles, geometries, and dosage forms with multiple drugs (polypills). Therefore, using this type of technology in the pharmaceutical industry will allow for the printing of limitless product designs and overcome the drawbacks of conventional pharmaceutical manufacturing associated with the production of dosage forms based on the ‘one-size-fits-all’ approach.

The work conducted herein used hot melt extrusion (HME) and FDM based 3D printing technology to manufacture different solid pharmaceutical dosage forms and novel medical devices. The starting materials prepared in this thesis were prepared using HME technology to incorporate different types of pharmaceutical drugs into various polymers, which were later utilised as feed materials for two different types of FDM based 3D printers: filament-based 3D printer and pellet based 3D printer. The assessment of the prepared drug loaded formulations regarding the mechanical properties, rheological characteristics, drug content and drug homogeneity was conducted to determine the quality of HME extrudates.

The first study examined the influence of various 3D printing processing parameters including (infill percentage, infill pattern, printing speed, and layer height) on 3D fabricated solid pharmaceutical dosage form (tablet) manufactured from commercially available drug free polymer; Poly lactic acid (PLA). The analysis assessed how these parameters influenced physical characteristics, including the weight, density, and dimensions of the resulting drug free tablets.

In the second study, the investigation and analysis focused on the influence of various 3D parameters on the in vitro drug release profile of 3D printed tablets. Initially, drug loaded polymers were prepared by incorporating caffeine into either the water soluble polymer polyvinyl alcohol (PVA) or the water insoluble polymer PLA utilising HME technology. These HME prepared drug loaded polymers (filaments) underwent characterisation to assess drug loading, filament diameter, extrusion capability, and thermal properties. Subsequently, FDM based 3D printer was employed to manufacture drug loaded tablets, employing different 3D parameters such as infill percentage, layer height, and infill patterns. Finally, the study analysed the impact of these parameters on the in vitro drug release of the fabricated tablets.

In the third study of this thesis, the feasibility of FDM based 3D printing technology to manufacture an oral solid dosage form (tablet) containing two different drugs Isoniazid (INH) and Pyridoxine Hydrochloride (PDX) was investigated. The drug combination is commonly used as a monotherapy for the treatment of tuberculosis infection (TB). All the pharmaceutical components of the dosage form were manufactured from FDA approved ingredients. The preparation of the drug loaded polymer formulation was initially performed by the HME process in two different ways. The first method involved loading the two drugs in a single polymer matrix to synthesise single layer tablet. The second method involved loading the drugs separately into two different extrudates and joining them during the 3D printing process using a dual extrusion 3D printer to manufacture a bilayer tablet. The prepared pharmaceutical drug loaded tablets of both types were analysed and compared in terms of in vitro drug release and physical properties.

In the fourth study, FDM based 3D printing technology was utilised to manufacture an implantable drug delivery device which was designed and 3D printed to be utilised as a prototype device for localised treatment of brain tumours. The implant is prepared from two different layers, the first one is composed of a blend of Poly (lactic-co-glycolic acid) (PLGA) loaded with Irinotecan (IRN) as a chemotherapeutic agent designed in the form of cone shaped protrusions with a dimension of 6 mm height and 5 mm base diameter. These protrusions are attached to a square shaped base layer with an edge length of 15 mm, printed from Ethylene-vinyl acetate (EVA) with a vinyl acetate content of 18.2%. The manufactured implant was characterised in terms of drug content, crystallinity, thermal properties, and in vitro drug release.

In the fifth study, FDM based 3D printing technology is utilised to manufacture a novel drug delivery device aimed at providing localised drug delivery of a chemotherapeutic agent for the post-surgical treatment of pancreatic cancer (PC). A cuboid-shaped device with dimensions of 35 mm in length, 12 mm in width, and 10 mm in height was manufactured from EVA 18.2% as a flexible polymer. The development and optimisation of computer-aided design (CAD) and FDM 3D printing of the device were analysed. Furthermore, the influence of different 3D printing parameters, including infill percentage, membrane thickness, pore size, and pore number on the in vitro drug release of the final optimised device was identified and analysed.

This thesis provides an overview of the feasibility of using FDM 3D printing for the synthesis of solid pharmaceutical dosage forms and contributes to the understanding of the advantages and limitations associated with this technique. Moreover, it provides insights into the promising applications of this technology in the manufacturing of medical devices that can be designed, customised, and modified to meet the specific requirements of individual conditions.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):