Development of 3D-Printed Captopril Mini-Tablets with customized release profiles for paediatric hypertension therapy

Hypertension, defined as a sustained increase in resting systolic and/or diastolic blood pressure (BP), represents a modifiable risk factor for cardiovascular and renal diseases that affect 5-10 % of paediatric patients. Captopril (CPT) is widely used for treating paediatric arterial hypertension; however, the smallest commercially available dosage form (25 mg) often necessitates off-label use, as paediatric doses range from 0.3-0.5 mg/kg. This study explores the development of immediate-release Mini-Tablets (MTs) of CPT for paediatric use via direct powder extrusion (DPE) 3D printing. The DPE technique enables precise control over dosage, shape, and size, facilitating personalized therapy. CPT-loaded MTs were fabricated using a 3DForMe® DPE 3D printer, incorporating polyvinyl alcohol (PVA) as a carrier polymer and hydroxypropyl methylcellulose (HPMC) as a co-polymer to ensure structural integrity and enhance drug encapsulation. MTs were produced with consistent size but varied infill percentages, allowing the formulation of immediate and sustained-release profiles from a single polymer mixture. Characterization of the MTs (weight uniformity, content uniformity both inter- and intra-batch, etc.) was performed to evaluate the effectiveness of the printing protocol and equipment in producing MTs. Dissolution and drug release studies were conducted in simulated gastric conditions (fasted and post-prandial states). MTs with 50 % and 75 % infill exhibited rapid dissolution and immediate drug release in fasted media, while other formulations demonstrated prolonged release in both gastric environments. These findings underscore the potential of DPE 3D printing to create flexible, precise, and customizable paediatric pharmaceutical formulations, addressing critical needs in personalized medicine and optimizing therapeutic outcomes.