Assembled fixed-dose combination tablet for hypertension: A modular design inspired by LEGO® architecture

Polypharmacy in chronic diseases like hypertension often compromises patient adherence and therapeutic success due to complex regimens. While conventional fixed-dose combination (FDC) tablets improve adherence, they lack the dose flexibility needed for personalized treatment. This study addresses this gap by developing and characterizing a novel, LEGO®-inspired assemblable FDC tablet system for customizable antihypertensive therapy. Using 3D-printed molds, individual, stackable modules containing either Amlodipine, Valsartan, or Hydrochlorothiazide (HCTZ) were created. The study evaluated two polymer matrices, revealing a critical dependence on the active pharmaceutical ingredient (API). Gelatin-based matrices were effective for Amlodipine and Valsartan, achieving rapid drug with USP dissolution standards; however, this matrix was incompatible release (>90% within 30 min) compliant with HCTZ. Conversely, an HPMC-based matrix successfully formulated HCTZ with a controlled-release profile but was unsuitable for the other two drugs. This work validates the proof-of-concept for a modular FDC system as a promising platform for personalized polypharmacy. However, it also highlights that achieving desired drug release profiles requires careful, API-specific polymer selection, presenting a key formulation challenge for this innovative approach.