Chronopharmaceutical tablet design for prednisone based on geometry and compression physics independent of excipient influence: a mechanistic approach to controlled release

Chronopharmaceutic drug delivery systems are designed to align the release of active substances with the body's biological rhythms, offering significant advantages in diseases with time-dependent symptom patterns. Delayed-release tablets are widely used in this field to achieve controlled drug release after a defined lag time, typically by modulating the composition of excipients. However, the reliance on excipient-based control may limit the flexibility and predictability of release profiles. This study is the first in the literature to focus on the mechanistic design of chronopharmaceutical tablets by exploring how physical tablet properties—specifically tablet geometry and compression physics—can independently control delayed drug release, without relying on excipient effects. By systematically varying tablet shape, size, and compression force, we aimed to establish a new formulation approach centered on the physical characteristics of the dosage form. Prednisone was selected as a model drug due to its common use in chronotherapy, where precisely timed drug release is essential to improve therapeutic outcomes. In vitro dissolution studies demonstrated that manipulation of tablet geometry and compression parameters effectively modulated lag time and drug release kinetics, independent of excipient composition. These findings suggest that optimizing the mechanistic properties of tablets provides a valuable strategy for the design of advanced chronopharmaceutical systems, potentially enhancing drug efficacy, patient comfort, and treatment adherence.