Khizer, Zara (2022) Novel Technological and Material Insights for Personalised Drug Delivery. Doctoral thesis, University of Huddersfield.

The thesis illustrates the clinical importance of personalised drug delivery devices and compare its effectiveness with the existing dosage forms of predefined strengths. The conventional system of manufacturing has its advantages and disadvantages. These methods are difficult to use in developing personalised drug delivery devices, but the recent emergence of 3D printing technologies has brought the development of personalised drug delivery devices near to reality. Among all the 3D printing technologies, fused deposition modelling (FDM) is the most commonly and widely used technique. However, the technology has limitation due to non-availability of pharmaceutical polymers approved by food and drug administration (FDA). Researchers have investigated already established pharmaceutical materials in FDM printing. Moreover, drug-loaded filaments feasible for FDM printing are not available commercially. Therefore, this thesis is aimed at firstly, to systematically review the role of 3D printing technology in developing personalised dosage forms. Secondly, feasibility of different polymers for hot-melt extrusion (HME) and for FDM printing was investigated by developing plasticiser-free HPMC polymers-based filaments using HME intended for FDM printing. Thirdly, a systematic review on the drug delivery routes available for the treatment of overactive bladder (OAB) was conducted. Lastly, plasticiser free filaments of PEO were extruded to develop gastroretentive floating drug delivery system for gabapentin to manage OAB.

A systematic review was conducted following preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines to identify the research studies contributing to the practicability of 3D printing technologies in developing novel personalised drug delivery devices. A total of 241 studies were included and were further categorised according to the types of 3D printing technologies. The review has comprehensively outlined the role of these technologies which will be helpful for researchers in the future.

Plasticiser free filaments were successfully extruded using three different grades of HPMC. Filaments were produced successfully and used to produce matrix tablets. The viscosity of HPMC had a discernible impact on the swelling, erosion, HPMC dissolution, drug release and pharmacokinetic findings. The highest viscosity grade (K100M) results in higher degree of swelling, decreased HPMC dissolution, low matrix erosion, decreased drug release and extended drug absorption profile.

Another systematic review was conducted to evaluate the various drug delivery strategies used in practice to manage OAB. A total of 24 studies reporting the development of novel formulations for the management of OAB were considered eligible and were further categorised according to the route of drug administration. The review found that various drug delivery routes (transdermal, intravesicular, oral, vaginal, and intramuscular) are used for the administration of drugs for managing OAB, however, the outcomes illustrated the marked potential of transdermal drug delivery route and limitations of using oral antimuscarinic drugs-based formulations due to their adverse effects.

Gastroretentive floating drug delivery system was developed to overcome the absorption related issues of gabapentin, an effective drug in the treatment of OAB. Plasticiser free PEO filaments were extruded. Tablets were printed with varying shell number and infill density to investigate the floating capacity. Among seven different tablet formulations F2 (2 shells, 0% infill) showed highest floating time i.e., more than 10 hours. Drug release studies showed the extended release of the drug in a 12-hour study. It was observed that the drug release was decreased with increase in infill density and shell number. However, among all the formulations, F2 was the optimum formulation with longer floating time and sustained release of the drug and was chosen for in vivo studies. The extended-release effect of PEO was also seen during the pharmacokinetic studies that made the drug to be absorbed into bloodstream over longer period. It was concluded that the in vitro, and in vivo studies showed successful fabrication of the tablets.

Overall, the results obtained can be a helpful resource in the future contributing to the further development, optimisation, and clinical translation of personalised drug delivery systems.

KHIZER - THESIS.pdf - Accepted Version
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