Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic circulation. Therefore, dissolution is a critical part of the drug-delivery process. The rate and extent of drug dissolution and absorption depend on the characteristics of the active ingredient as well as properties of the dosage form. Just as importantly, characteristics of the physiological environment such as buffer species, pH, bile salts, gastric emptying rate, intestinal motility, and hydrodynamics can significantly impact dissolution and absorption. While significant progress has been made since 1970 when the first compendial dissolution test was introduced (USP apparatus 1), current dissolution testing does not take full advantage of the extensive physiologic information that is available. For quality control purposes, where the question is one of lot-to-lot consistency in performance, using nonphysiologic test conditions that ma...

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Physiological Parameters for Oral Delivery and in Vitro Testing

Abstract As the function of the gastrointestinal tract is to a large degree mechanical, it has become increasingly popular to acquire distensibility data in motility research based on various parameters. Hence it is important to know on which geometrical and mechanical assumptions the various parameters are based. Currently, compliance and tone derived from pressure‐volume curves are by far the most often used parameters. However, pressure‐volume relations obtained in tubular organs must be carefully interpreted as they provide no direct measure of luminal cross‐sectional area and other variables useful in plane stress and strain analysis. Thus, erroneous conclusions concerning tissue distensibility may be deduced. Other parameters, such as wall tension, stress and strain, give more useful information about mechanical behaviour. Distensibility data procure significance in fluid mechanics and in the study of tone, peristaltic reflexes, and mechanoreceptor kinematics. Such data are needed for the determination of the interaction between stimulus, electrical responses in neurons and the mechanical behaviour of the gut. Furthermore, from a clinical perspective, investigation of visco‐elastic properties is important because GI diseases are associated with growth and remodelling. For example, prestenotic dilatation, increased collagen synthesis, dysmotility and altered distensibility are common features of obstructive diseases. The purpose of this review is to discuss the physiological and clinical importance of acquiring biomechanical data, distensibility parameters and interpretation of these results and their associated errors. We will also discuss some aspects of the relationship between morphology, growth and biomechanics. Finally, we will outline a number of techniques to study the mechanical properties of the GI tract.

Biomechanics of the gastrointestinal tract

Obscure gastrointestinal (GI) bleeding, Crohn disease, Celiac disease, small bower tumors, and other disorders that occur in the GI tract have always been challenging to be diagnosed and treated due to the inevitable difficulty in accessing such a complex environment within the human body. With the invention of wireless capsule endoscope, the next generation of the traditional cabled endoscope, not only a dream has come true for the patients who have experienced a great discomfort and unpleasantness caused by the conventional endoscopic method, but also a new research field has been opened to develop a complete miniature robotic device that is swallowable and has full functions of diagnosis and treatment of the GI diseases. However, such an ideal device needs to be equipped with a highly accurate localization system to be able to exactly determine the location of lesions in the GI tract and provide essential feedback to an actuation mechanism controlling the device's movement. This paper presents a comprehensive overview of the localization systems for robotic endoscopic capsules, for which the motivation, challenges, and possible solutions of the proposed localization methods are also discussed.

/pdf/a-review-of-localization-systems-for-robotic-endoscopic-1h7833k2gi.pdf

A Review of Localization Systems for Robotic Endoscopic Capsules

Receivers, which may be external or implantable, are provided. Aspects of receivers of the invention include the presence of one or more of: a high power-low power module; an intermediary module; a power supply module configured to activate and deactivate one or more power supplies to a high power processing block; a serial peripheral interface bus connecting master and slave blocks; and a multi-purpose connector. Receivers of the invention may be configured to receive a conductively transmitted signal. Also provided are systems that include the receivers, as well as methods of using the same. Additionally systems and methods are disclosed for using a receiver for coordinating with dosage delivery systems.

Body-associated receiver and method

Compositions, systems and methods that allow for the detection of the actual physical delivery of a pharmaceutical agent to a body are provided. Embodiments of the compositions include an identifier and an active agent. The invention finds use in a variety of different applications, including but not limited to, monitoring of therapeutic regimen compliance, tracking the history of pharmaceutical agents, etc.

Pharma-informatics system

Based on a 2D-array of 16 cylindrical Hall sensors and a permanent magnet, a tracking system with five degrees of freedom is analysed in this paper. The system accuracy is studied, including offset drifts, sensitivity mismatches and the number of sensors. A detection distance as large as 14 cm (during 1 h without calibration) is achieved using a magnet of 0.2 cm3. The position and orientation of the marker is displayed in real time with a sampling frequency up to 50 Hz. The sensing system is small enough to be hand-held and can be used in a normal environment.

Tracking system with five degrees of freedom using a 2D-array of Hall sensors and a permanent magnet

A system and method for monitoring and stimulating GI motility is provided One or more capsules (or motility markers) may be ingested by a patient for passage through the GI tract Each capsule may contain an emitting coil which produces an AC magnetic field, or a permanent magnet An external sensing device comprising multiple magnetic field sensors is used to measure, among other data, the position of the ingested capsules within the GI tract As signals from the magnetic field sensors are acquired, an iterative algorithm continuously calculates the magnetic momentum and position of each capsule in real time The position of each capsule may be defined by five coordinates (x, y, z, 6, cp) representing three translations and two rotations This data may be displayed in real time or saved for further processing When one or more capsules reach a segment of the,' GI tract that has been identified for treatment, the capsule(s) may be subjected to an external magnetic field applied by a generator or other device The applied magnetic field may result in movements of the capsule with respect to the enteric nervous system so as to trigger the natural, physiological propulsive reflexes of the GI tract

System and method for monitoring and stimulating gastro-intestinal motility

The Magnet Tracking System (MTS) is a minimally-invasive technique of continuous evaluation of gastrointestinal motility. In this study, MTS was used to analyse colonic propulsive dynamics and compare the transit of a magnetic pill with that of standard radio-opaque markers. MTS monitors the progress in real time of a magnetic pill through the gut. Ten men and 10 women with regular daily bowel movements swallowed this pill and 10 radio-opaque markers at 8 pm. Five hours of recordings were conducted during 2 following mornings. Origin, direction, amplitude and velocity of movements were analysed relative to space–time plots of the pill trajectory. Abdominal radiographs were taken to compare the progress of both pill and markers. The magnetic pill lay idle for 90% of its sojourn in the colon; its total retrograde displacement accounted for only 20% of its overall movement. Analysis of these movements showed a bimodal distribution of velocities: around 1.5 and 50 cm min–1, the latter being responsible for 2/3 of distance traversed. There were more movements overall and more mass movements in males. Net hourly forward progress was greater in the left than right colon, and greater in males. The position of the magnetic pill correlated well with the advancement of markers. MTS showed patterns and propulsion dynamics of colonic segments with as yet unmet precision. Detailed analysis of slow and fast patterns of colonic progress makes it possible to specify the motility of colonic segments, and any variability in gender. Such analysis opens up promising avenues in studies of motility disorders.

Colonic movements in healthy subjects as monitored by a Magnet Tracking System.

Although other methods exist for monitoring gastrointestinal motility and contractility, this study exclusively provides direct and quantitative measurements of the forces experienced by an orally ingested pill. We report motive forces and torques calculated from real-time, in vivo measurements of the movement of a magnetic pill in the stomachs of fasted and fed humans. Three-dimensional net force and two-dimensional net torque vectors as a function of time data during gastric residence are evaluated using instantaneous translational and rotational position data. Additionally, the net force calculations described can be applied to high-resolution pill tracking acquired by any modality. The fraction of time pills experience ranges of forces and torques are analyzed and correlate with the physiological phases of gastric digestion. We also report the maximum forces and torques experienced in vivo by pills as a quantitative measure of the amount of force pills experience during the muscular contractions leading to gastric emptying. Results calculated from human data are compared with small and large animal models with a translational research focus. The reported magnitude and direction of gastric forces experienced by pills in healthy stomachs serves as a baseline for comparison with pathophysiological states. Of clinical significance, the directionality associated with force vector data may be useful in determining the muscle groups associated with gastrointestinal dysmotility. Additionally, the quantitative comparison between human and animal models improves insight into comparative gastric contractility that will aid rational pill design and provide a quantitative framework for interpreting gastroretentive oral formulation test results.

https://www.pnas.org/content/pnas/107/18/8201.full.pdf

Understanding gastric forces calculated from high-resolution pill tracking

Background: Fluoroscopic verification of nasogastric (NG) feeding tube placement is inconvenient and involves radiation exposure. We tested whether the position of an NG tube can be assessed reliably by a recently introduced magnet-tracking system. Methods: A small permanent magnet was attached at the end of an NG tube and its position was monitored using an external sensor array connected to a computer. NG tube trajectory, spontaneous movements of the magnet, and its position relative to the lower esophageal sphincter (LES) and xiphisternum were assessed in 22 healthy subjects and compared with esophageal manometry. In 12 subjects, localization of the magnet was also compared with fluoroscopy. Results: Magnet-tracking displayed NG tube tip movement reproducibly as it moved vertically in the esophagus and then laterally into the stomach. Compared with manometry, the accuracy and sensitivity of magnet tracking for localization of the NG tube tip, above or below the diaphragm, were 100%. Compared with fluor...

Vincent Schlageter

Papers

Tracking system with five degrees of freedom using a 2D-array of Hall sensors and a permanent magnet

System and method for monitoring and stimulating gastro-intestinal motility

Colonic movements in healthy subjects as monitored by a Magnet Tracking System.

Understanding gastric forces calculated from high-resolution pill tracking

Noninvasive verification of nasogastric tube placement using a magnet-tracking system: a pilot study in healthy subjects.