The treatment of chronic conditions increasingly necessitates multidrug regimens targeting multiple pathological pathways. Although polypharmacy enhances therapeutic effectiveness, it often complicates medication adherence, dose optimisation, and treatment personalisation. Fixed-dose combinations (FDCs) were developed to simplify regimens by consolidating multiple drugs into a single dosage form, thus reducing pill burden and improving compliance. However, traditional FDCs offer limited flexibility for individualised dose adjustments, timing modifications, and the integration of pharmacogenomic data. As medicine advances toward precision and patient-centric care models, the rigidity of conventional dosage forms presents a growing limitation.

In response, this work presents the FlexiPill platform: a modular, 3D-printed oral dosage form that enables flexible, individualised polypharmacy. Using fused deposition modelling (FDM), drug-loaded thermoplastic filaments were extruded and printed into discrete modules, each engineered with a specific release profile. These modules can be physically combined into tailored polypills at or near the point of care, eliminating the need for reformulation and enabling rapid adaptation to patient-specific therapeutic requirements. This modular approach addresses the clinical need for personalisation while remaining compatible with pharmaceutical manufacturing and regulatory constraints.

Three case studies were undertaken to evaluate the platform’s versatility. In the first, theophylline was selected to explore controlled release through modular formulation and a structured Design of Experiments (DoE), varying parameters such as drug loading, infill density, and immediate-to-sustained-release (IR-to-SR) ratios. The second study involved a personalised analgesic polypill combining paracetamol, ibuprofen, and caffeine, each embedded in tailored polymer matrices for distinct release profiles. The third case study extended the platform to gastroretentive delivery with a cardiovascular polypill comprising propranolol hydrochloride, enalapril maleate, and hydrochlorothiazide, targeting narrow absorption windows. Across all case studies, a consistent suite of analytical techniques was employed, including dissolution testing, thermal analysis (DSC, TGA), chemical analysis (FTIR), structural characterisation (SEM, XRD), and mechanical testing. Modified Principal Component Analysis (M-PCA) was applied to interpret dissolution profiles, while Dynamic Vapour Sorption (DVS) assessed humidity-related stability and release performance.

The findings from all three case studies confirmed the functional robustness and adaptability of the FlexiPill platform. In the first case study, drug release profiles for theophylline were significantly influenced by both drug load and IR-to-SR ratios (p < 0.05). However, higher drug loads negatively affected filament viscosity, resulting in weight variation, poor print resolution, and formulation instability. In the second study, the analgesic polypill successfully combined paracetamol (55% w/w), ibuprofen, and caffeine—three APIs with divergent release and stability requirements—into a single dosage form. Paracetamol, embedded in a 1:1 blend of PVP K40 and Eudragit EPO, demonstrated rapid release under acidic conditions with over 85% release after one hour in acidic media, but less than 30% in alkaline conditions (p = 0.00002), confirming effective pH-dependent release and taste masking. Ibuprofen, incorporated into a gastro-resistant Eudragit L100-55 matrix, released less than 1% in acidic medium over 24 hours, with more than a tenfold increase in alkaline medium, confirming successful enteric protection. Caffeine, embedded in a fast-dissolving polyvinyl alcohol (PVA) matrix, exhibited rapid onset with 84% released within the first 30 minutes. The third case study demonstrated the platform’s gastroretentive capabilities: propranolol was incorporated into a floating low-density printlet that maintained gastric retention for up to nine hours and released 96% of the drug within this period. Enalapril was printed at 150°C using a modified thermoplastic polymer matrix, maintaining chemical integrity despite its thermosensitive nature. Hydrochlorothiazide was delivered in an immediate-release matrix, achieving over 90% release within the first hour.

Collectively, this research establishes the FlexiPill platform as a versatile, scalable, and clinically relevant solution for personalised oral drug delivery. By enabling modular design, custom release control, and adaptable polypill assembly, the system offers a practical route toward integrating personalised medicine within existing pharmaceutical manufacturing frameworks. This approach holds promise for improving treatment adherence, safety, and therapeutic outcomes in complex disease management.