Hu, Mengyang; (2025) Inkjet Printing of Nanocrystals onto Polymeric Substrates for Oral Drug Delivery. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Improving the delivery of poorly water-soluble drugs remains a major challenge in pharmaceutical development. This thesis explores the application of piezoelectric inkjet printing (PIJ) to formulate nifedipine (NIF), a model poorly soluble drug, as nanocrystals deposited onto polymeric substrates for enhanced oral delivery. The study aimed to assess PIJ’s potential for precise dosing and improved dissolution. A stable NIF nanosuspension (200–500 nm) was developed using precipitationultrasonication and printed using a Jetlab 4 PIJ system. Substrate development compared solvent-cast ethyl cellulose (EC) films with 3D-printed hydrogels (PEGDA/PEGDMA). Thermal and mechanical analyses confirmed the suitability of EC films, while 3D-printed hydrogels were optimized via Design of Experiments (DoE), which identified polymer type as the most influential factor affecting thermal and shrinkage properties. NIF deposition was confirmed by Scanning Electron Microscopy (SEM), which showed that while discrete nanocrystals could be retained on high-energy surfaces, printed films on polymeric substrates often exhibited particle aggregation, highlighting the impact of substrate properties and drying dynamics on post-printing morphology. HPLC analysis validated drug quantification methods at low doses. Inkjet printing achieved effective, though variable, drug loading compared to manual pipetting. In vitro release studies showed significantly faster initial dissolution from inkjet-printed EC films versus pipetted ones, with release kinetics fitting a first-order model, suggesting the potential for rapidrelease formulations. Overall, this study demonstrates the feasibility of PIJ for fabricating nanocrystal-based drug films. By optimizing formulation, printing, and substrate parameters, and investigating morphological outcomes via SEM, the work highlights PIJ’s potential as a platform for improving delivery of poorly soluble drugs and enabling precise, potentially personalized dosing. Further research, particularly in vivo studies, is needed to confirm clinical applicability.

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