Digital Pills and Ingestible Biosensors: Redefining Drug Adherence Science

Background: Medication non-adherence remains a critical global healthcare challenge, contributing to poor clinical outcomes, increased hospitalizations and rising healthcare costs. Conventional adherence assessment tools self-reports, pill counts, pharmacy refills are indirect and error-prone. Digital pills integrated with ingestible biosensors have emerged as a disruptive innovation offering objective, real-time confirmation of drug ingestion. Objective: This review critically examines the scientific principles, technological architectures, clinical applications, regulatory landscape and ethical considerations of digital pills and ingestible biosensors, with a focus on research trends from 2020-2025. Methods: A narrative and trend-based systematic review was conducted using PubMed, Scopus and Web of Science databases following PRISMA-informed principles. Peer-reviewed articles published between January 2020 and June 2025 were analyzed. Results: Ingestible biosensors demonstrate high accuracy in detecting medication ingestion and physiological parameters, particularly in psychiatry, cardiology, tuberculosis and transplant medicine. However, challenges persist related to cost, data privacy, patient autonomy, scalability and long-term clinical validation. Conclusion: Digital pills represent a paradigm shift in adherence science, transitioning from probabilistic estimates to direct biological confirmation. Future research must prioritize patient-centered design, ethical governance and integration with digital health ecosystems