ESF Thüringen - Liste der Vorhaben Förderperiode 2014-2020

Drug Delivery System - In vivo tracking of tablets and capsules
 

Drug Delivery System

In vivo tracking of tablets and capsules

High resolution magnetic monitoring system for dissolution and bioavailability analyses

 

Matesy is one of the few manufacturers able to offer real-time positioning of capsules and tablets with the ability of a passive or remote-controlled release of any formulation – free of radiation! The time frame and path of the passively dissolving tablet as well as the transit time of each individual GI part can be recorded. The travelled path of the tablet can be visualized and motility patterns can be evaluated. Investigations of drug / drug and drug / food interactions are possible to perform.

 

Overview

 

How can a  capsule be  located inside  the GI tract ?
How can  the tablet  dissolution be  analyzed?
How can the  drug release  be controlled?

 

3D-magma  

Magnetic marker monitoring system

 

Introduction

In order to track a magnetic marker inside of the gastrointestinal tract of humans and animals the magnetic marker monitoring system 3D-magma was developed. The system contains several highly sensitive magnetic field sensors (anisotropic magneto resistive) which are arranged contactlessly above the abdomen of the volunteer. For dog and other animal studies we use an adapted sensor arrangement around a hammock. The 3D-magma measures the magnetic marker and calculates its three dimensional position and orientation using nonlinear optimization algorithms.

 

3D-magma set-up for human studies

3D-magma set-up for human studies

3D-magma set-up for dog studies

3D-magma set-up for dog studies

 

The accuracy of the marker detection relies on the available magnetic field strength at the different sensor positions induced by the magnetic marker and on the number of sensors. Within the entire gastrointestinal tract the maximum absolute position error is less than ± 5 mm (resolution: less than 1 mm) and the absolute orientation error less than± 2 ° (resolution: < 0.5 °).

 

Performance calculations with the 3D-magma software

3D path of the magnetic marker inside of the gastrointestinal tract of a volunteer (human)

3D path of the magnetic marker inside of the gastrointestinal tract of a volunteer (human)

Travelled path of the magnetic marker inside of the gastrointestinal tract of a dog

Travelled path of the magnetic marker inside of the gastrointestinal tract of a dog

 

The 3D-magma system measures and calculates the following criteria as indicator for the positioning of the magnetic marker:

 

  • Travelled path of the magnetic marker in real-time
  • Motility patterns
  • Transit times of each gastrointestinal part

 

3D path of the magnetic marker inside of the gastrointestinal tract of a volunteer (human)

3D path of the magnetic marker inside of the gastrointestinal tract of a volunteer (human)

Change of the frequency during the passage from the stomach (6 min -1) to the small intestinum (13 - 15 min -1)

Change of the frequency during the passage from the stomach (6 min -1) to the small intestinum (13 - 15 min -1)

 

At any time the user is able to follow the exact position of the magnetic marker inside of the human’s or animal’s gastrointestinal tract. It is also possible to determine the dissolution status as a result of the tablet’s magnetic moment measurement.

 

maars

Magnetic active agent release system

 

Technical Background

The drug release system comprises a magnetic carrier for the delivery and a system for the release initiation. The carrier consists of semi-hard and soft magnetic components. In the magnetized status, the semi-hard magnetic material induces a magnetic flux being partly conducted by the soft magnetic components.

This part of the flux establishes a closed loop inside of the wall of the capsule and excites magnetic forces between the metallic parts to keep the capsule closed. The part of the magnetic flux induced by the semi-hard material (not closed by the soft magnetic components) constitutes a stray field that can be used for an exact localization by the magnetic monitoring system (3D-magma).

In the non magnetized status of demagnetization the magnetic forces disappear. Caused by the intestinal motility the carrier disintegrates, releasing the carried drug. The single components leave the gastrointestinal tract via naturalis. All elements are coated with a bioinert polymer layer.

 

Drug Delivery System - In vivo tracking of tablets and capsules

Step 1: Application of the capsule -> Step 2: Real time monitoring of the capsule -> Step 3: Controlled drug release into the target volume

 

Benefits

  • Bioavailability studies 
  • Identification of “absorption windows” 
  • Drug targeting “Proof-of-concept” studies 
  • Possible without the development of any formulation 
  • Reduction of the galenic development
  • Optimization of the formulation of new and already used active agents

Illustration of the controlled drug release inside a target volume.

Illustration of the controlled drug release inside a target volume.

 

Dissolution Studies

The dissolution analysis of pharmaceutical agents in in vivo studies in humans and animals has become an important part for the development of new pharmaceutical products. In respect of such studies we were able to develop a method, that allows us to measure and record the 3D-path as well as the respective time of the passively dissolving tablet inside of the gastrointestinal tract. 

The technology is based on the use of magnetic fields. In cooperation with pharmaceutical partners we designed a tablet containing a large number of very small homogeneously distributed magnets. At this state the tablet generates a constant high magnetic field that can be detected with our 3D-magma systems. During the dissolution process the magnets are being released. Due to their magnetic forces the magnets begin to move toward each other resulting in a measurable decrease of magnetic field strength.

Using this method the developer is able to investigate the dissolution process in vivo and in real-time in order to perform exact and integrated dissolution analyses.

Illustration of the dissolution process throughout the different parts of the GI tract.

Illustration of the dissolution process throughout the different parts of the GI tract.

 

Dietzel el al. (2012). Magnetic Active Agent Release System (MAARS): evaluation of a new way for a reproducible, externally  controlled drug release into the small intestine. Journal of Controlled Release (05/2012)