Digitizing Medicines for Remote Capture of Oral Medication Adherence Using Co‐encapsulation

Abstract

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.

Real‐Time and Wireless Assessment of Adherence to Antiretroviral Therapy With Co‐Encapsulated Ingestion Sensor in HIV‐Infected Patients: A Pilot Study

“…This was designed to address issues related to real‐time data handling, co‐encapsulation, patch use, and medication delivery along with personalized text messaging feedback. Co‐encapsulation was performed by investigational drug pharmacists per manufacturer guidelines and as summarized by Browne et al ., using the same size gelatin cap for all medications, regardless of their size. Bioavailability of utilized co‐encapsulated ARVs was previously presented .…”

“…Enrolled individuals had one of the ARV pills they were routinely taking co‐encapsulated during the 16 weeks of study, a process that we performed per manufacturer guidelines by an investigational drug pharmacist . Participants were provided instructions on how to use the PDHF system, including patch use and synchronization with the patch and mobile devices.…”

Outcome measures for adherence data from a medication event monitoring system: A literature review

“…For example, a patient could open the bottle and either not take any or more than the appropriate dose. Validation of MEMS data may become possible with compliance capsules with an ingestion sensor . This is a new method, where the sensor signals when the drug is taken.…”

Use of a Digital Medication Management System for Effective Assessment and Enhancement of Patient Adherence to Therapy (ReX): Feasibility Study (Preprint)

“…US) [20] or ingestible sensors (Proteus Digital Health, Inc.) [21], that can be detected following ingestion, by a bodyworn patch that collects physiological and behavioral metrics, and transfers this information to a mobile device. Although these methods indeed track the pills after ingestion in the patient's body, they cannot eliminate overdose nor prevent abuse by confirming the patient's identity.…”

“…Electronic monitoring devices have been shown to provide good quality information on adherence rates [12] and hold promise for improving adherence, as demonstrated in multiple clinical trials [17,20,21]. Methods which involve reinforcement interventions were successful in improving patient's cooperation and adherence behaviors.…”