ABSTRACT:
Programmable oral drug delivery systems integrate pharmaceutical formulations with intelligent ingestible technologies to regulate drug administration according to predetermined instructions or physiological signals. Unlike conventional oral dosage forms, they can provide spatial and temporal control of drug release through stimuli-responsive materials, reservoirs, sensors, actuators, microelectromechanical systems (MEMS), and wireless or electronic control. These systems can respond to physiological cues such as pH, enzymes, temperature, pressure, transit time, disease-associated biomarkers and inflammatory conditions, or to external triggers including magnetic fields, ultrasound, radiofrequency signals, light and electrical inputs. Time-programmed and on-demand systems further enable predetermined, sequential or pulsatile release. Recent progress in microfabrication, three-dimensional (3D) and four-dimensional (4D) printing, microfluidics, bioelectronics, artificial intelligence (AI), and biodegradable materials has expanded opportunities for personalized therapy and precision medicine. However, device miniaturization, manufacturing complexity, biocompatibility, power supply, cybersecurity, regulatory requirements and scalable production remain important barriers to clinical translation. This review discusses the principles, materials, trigger mechanisms, device architectures, fabrication methods, evaluation approaches, therapeutic applications, and regulatory considerations of programmable oral drug delivery systems, with emphasis on recent technological developments and future clinical opportunities.