Digitizing Medicines for Remote Capture of Oral Medication Adherence Using Co-encapsulation.
High-resolution measurement of medication adherence is essential to personalized drug therapy. A US Food and Drug Administration (FDA)-cleared device, using an edible ingestion sensor (IS), external wearable patch, and paired mobile device can detect and record ingestion events. Oral medications must be combined with an IS to generate precise "digitized-medication" ingestion records. We developed a Good Manufacturing Practice protocol to repackage oral medications with the IS within certified Capsugel capsules, termed co-encapsulation (CoE). A randomized bioequivalence study of CoE-IS-Rifamate (Isoniazid/Rifampin 150/300 mg) vs. native-Rifamate was conducted in 12 patients with active Mycobacterium tuberculosis and demonstrated bioequivalence using the population method ratio test (95% confidence interval). Subsequently, CoE-IS-medications across all biopharmaceutical classes underwent in vitro dissolution testing utilizing USP and FDA guidelines. CoE-IS medications tested met USP dissolution specifications and were equivalent to their native formulations. CoE combines oral medications with the IS without altering the quality of the native formulation, generating "digitized" medications for remote capture of dosing histories.
University of California, San Diego School of Medicine, Division of Infectious Diseases, San Diego, California, USA.,
University of Florida, College of Pharmacy and Emerging Pathogens Institute, Gainesville, Florida, USA.,
Research and Analytic Services, Sharp Clinical Services, Pennsylvania, USA.,
University of California, San Diego School of Medicine, Division of Infectious Diseases, San Diego, California, USA. Gilead Sciences, Gilead Sciences, Inc., Foster City, California, USA.,
University of California, San Diego Department of Medicine, Research Pharmacy, San Diego, California, USA.,
San Diego County Health and Human Services Agency, San Diego, California, USA. Centers for Disease Control, National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, Georgia, USA.,
Proteus Digital Health, Inc., Redwood City, California, USA.,
University of California, San Diego School of Medicine, Division of Infectious Diseases, San Diego, California, USA.
Stanford University, Stanford, California, USA.
Pub Type(s)Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't