AbstractThe recent years have witnessed the rise of three-dimensional printing (3DP) technologies in several fields, spanning from healthcare to automotive and construction. In particular, 3DP has aroused much interest in pharmaceutics, mainly for its potential to deliver personalised drug products on-demand, thus revolutionising the way medicines are designed, manufactured, and dispensed.
Among the several 3DP technologies currently available, stereolithography (SLA) is particularly attractive because of key advantages such as offering an unrivalled printing resolution and compatibility with thermolabile drugs. On the other hand, since conventional SLA 3D printers are designed to operate with large volumes of a single material, significant throughput limitations remain. This, coupled with the limited choice of biocompatible polymers and photoinitiators available, hold back the pharmaceutical development of such technology. Furthermore, limited data on SLA 3D printed tablets physical properties are available. Therefore, this research project aimed to address the abovementioned problems using a step-by-step approach.
First, a novel SLA apparatus was developed to enhance throughput and improve formulation development cost-effectiveness, thus enabling to use up to 12 different materials simultaneously and reducing sample amount by 20 times. As a result, formulation development cost was reduced by 95%. Then, such high-throughput SLA apparatus was used to conduct a systematic printability screening on 156 novel photopolymer formulations, to identify candidates with optimal printability for the subsequent drug loading studies. Polyethylene glycol diacrylate 700 and diphenyl-(2,4,6-trimethylbenzoyl)-phosphine oxide were identified as lead photopolymer and photoinitiator, respectively, while propylene glycol was found to be a suitable liquid filler to be incorporated in the photopolymer resin formulations. Lastly, 43 drug-loaded formulations containing theophylline, warfarin, or warfarin sodium were 3D printed into solid oral dosage forms and thoroughly characterised. Dosage forms’ physical properties, namely hardness and friability, were found to be compliant with current Pharmacopoeia standards. Furthermore, potassium bicarbonate was incorporated, for the first time, in the photopolymerisable resin to tune drug release via effervescence in the acidic simulated gastric medium.
In conclusion, the findings of this research indicate that SLA 3D printing can be successfully used to manufacture quality solid oral dosage forms loaded with clinically relevant drug dosages, with the potential to deliver personalised medicine at the point of care.
|Date of Award
|Craig Russell (Supervisor) & Daniel Kirby (Supervisor)
- Personalised medicine
- Biocompatible Photopolymers
- Solid Oral Dosage Forms