A structure dosage form approach for solubility and dissolution rate enhancement

Despite various attempts at solubility enhancement and advances in formulation technologies, improving the bioavailability of poorly water-soluble compounds remains a significant challenge. Melt extrusion deposition (MED®) 3D printing is an additive manufacturing technology developed specifically for pharmaceutical applications to produce dosage forms with complex internal and external geometrical structures. This technology provides novel solutions and unique opportunities for enhancing the bioavailability of poorly soluble compounds through structurally engineered tablets and supports the development of patient-centric medications tailored to meet diverse clinical needs. This study describes the use of MED® technology to formulate a poorly water-soluble model compound, enhance its solubility, and modulate its release profile to achieve immediate release (IR), extended release (ER), and extended-plus-delayed release (ER + DR). After the model compound was formulated as an amorphous solid dispersion (ASD), the solubility in distilled water increased to around 60 μg/mL, representing up to a 4-fold increase relative to its thermodynamic solubility (∼15 μg/mL). Utilizing the same ASD drug-core formulation, two distinct 3D-printed tablet structures were designed and fabricated: a mesh structure for an IR tablet and a multi-compartment structure with variable-thickness delayed-release layers for an ER + DR tablet. These designs enabled tailored release profiles for the poorly water-soluble model compound. This structure-driven approach via MED® 3D printing enables both solubility enhancement and precise release modulation for poorly water-soluble drugs, thereby providing a new pathway for the rational design and efficient development of tablet dosage forms.