Abstract

Hypertension is highly prevalent worldwide, affecting approximately one in three adults. The pathophysiology of hypertension is multifactorial, which led recent guidelines to recommend the initiation of treatment with more than one antihypertensive agent. This exacerbates the existing issue of polypharmacy, particularly among geriatric patients. Polypharmacy can lead to a reduction in patient adherence to the treatment. As a result, many clinical studies have investigated using fixed-dose combinations to address this issue. These studies have demonstrated the effectiveness of a polypill in improving patient adherence. However, a polypill limits the flexibility for dose titration and personalisation of treatment. Therefore, when 3D printing was first introduced to pharmaceutical formulation, researchers recognised the potential of this technology for drug personalisation and the creation of more flexible drug combinations. Nonetheless, regulatory concerns still limit the translation of these research efforts into clinical applications that can benefit the patient. Consequently, this study seeks to bridge the existing gap by identifying a balanced approach between regulatory requirements and the concept of personalised drug combinations. The Flexipill is a flexible dose combination that does not require printing at the pharmacy level. It can be printed at a quality-controlled facility and assembled according to patient needs at the point of care. In this work, an antihypertensive Flexipill was printed, with each unit having different drug release profiles and formulation requirements. The propranolol HCl unit was printed as a floating unit to improve its solubility and bioavailability. It floated for 9 h, releasing over 90 % of the drug content. The enalapril maleate unit was formulated to avoid thermal degradation by printing at 150 °C, which is lower than its degradation temperature. Moreover, hydrochlorothiazide was formulated to provide immediate release of over 90 % of the drug within the first hour. [Abstract copyright: Copyright © 2025. Published by Elsevier B.V.]