Jeff Shimizu

Investigation of pH and Temperature Profiles in the GI Tract of Fasted Human Subjects Using the Intellicap® System

Gastrointestinal (GI) pH and temperature profiles under fasted-state conditions were investigated in two studies with each 10 healthy human subjects using the IntelliCap(®) system. This telemetric drug delivery device enabled the determination of gastric emptying time, small bowel transit time, and colon arrival time by significant pH and temperature changes. The study results revealed high variability of GI pH and transit times. The gastric transit of IntelliCap(®) was characterized by high fluctuations of the pH with mean values ranging from pH 1.7 to pH 4.7. Gastric emptying was observed after 7-202 min (median: 30 min). During small bowel transit, which had a duration of 67-532 min (median: 247 min), pH values increased slightly from pH 5.9-6.3 in proximal parts to pH 7.4-7.8 in distal parts. Colonic pH conditions were characterized by values fluctuating mainly between pH 5 and pH 8. The pH profiles and transit times described in this work are highly relevant for the comprehension of drug delivery of solid oral dosage forms comprising ionizable drugs and excipients with pH-dependent solubility.

A novel ingestible electronic drug delivery and monitoring device

BACKGROUND We developed an ingestible electronic drug delivery and monitoring system. This system includes an electronic capsule comprising a drug reservoir, a pH and temperature sensor, a microprocessor and wireless transceiver, a stepper motor, and batteries. The location of the capsule in the gut derived from pH data can be monitored in real time. The stepper motor can be remotely actuated to expel the contents of the drug reservoir. OBJECTIVES First human study. DESIGN Two consecutive observational studies. SETTING University medical center. SUBJECTS Twenty healthy volunteers. INTERVENTIONS Study I: Ingestion and passage of the capsule. Study II: Ingestion and passage of the capsule, loaded with (99m)technetium-pertechnetate ((99m)Tc); remotely actuated expulsion of (99m)Tc in the gut. MAIN OUTCOME MEASUREMENTS Study I: Safety, tolerability, and functionality (wireless pH and temperature recording). Study II: Tracing of the capsule and expulsion and distribution of (99m)Tc from the drug reservoir by scintigraphy. Correlating location pH with scintigraphy. RESULTS Study I: Ingestion and passage of the capsule was safe and well tolerated. Transmitted pH and temperature data were received by the recorder in 96.5% ± 3%. Study II: pH-determined passage of the esophagogastric, gastroduodenal, and ileocolonic junction correlated well with scintigraphy. Expulsion of (99m)Tc from the capsule was successful in 9 of 10 subjects. LIMITATIONS Subjects with relatively low body mass index. CONCLUSIONS This electronic drug delivery and monitoring system may be a promising tool for targeted delivery of substances to well-defined areas of the GI tract.

First in Human Study With a Novel Ingestible Electronic Drug Delivery and Monitoring Device: The Intellicap

BACKGROUND: Highly predictable intraluminal delivery of drugs to a well-defined area of the gut may be beneficial for the development and testing of new drugs as well as for clinical use in luminal diseases of the gut and diseases requiring high drug concentrations in the portal system. We developed an ingestible electronic drug delivery and monitoring device, the IntelliCap, to meet these demands. The IntelliCap comprises a 300 μl drug reservoir, a pHand temperature sensor, a stepper motor, and a transceiver for 2-way real time wireless communication. Data are relayed via a data recorder to a computer. Changes in pH and temperature can be used to indicate the location of the IntelliCap in the gut and control drug delivery.