Formulation tech goes Enterion
friend as the technology helps drug companies assess the
feasibility of oral modified release formulations.
Developed by Nottingham University spin off Pharmaceutical Profiles, the Enterion capsule is an engineered device that assess the bioavailability of drugs in different parts of the gastrointestinal (GI) tract.
"The advantage is it gives you a profile of human drug absorption of your drug and you can go away and formulate a drug with optimum bioavailability," Pharmaceutical Profiles marketing and product development vice president Dr Karen Jones told in-PharmaTechnologist.com at the American Association of Pharmaceutical Scientists (AAPS) conference in San Diego last week.
Most oral immediate release dosage forms are readily absorbed in the upper GI tract but the bioavailability of different drugs vary in the distal regions due to such things as pH, fluid volume, gut wall enzymes, transporters, permeability and residence time.
In order to develop a formulation that relies on drug delivery for more than a few hours, after transit through the proximal GI regions, the formulation must require the drug to be bioavailable to the lower GI tract of the ileum and colon.
The Enterion capsule has been designed with this in mind.
A round-ended capsule, 34mm in length and 11mm in diameter - equivalent in size to a 000 capsule - the Enterion capsule contains a drug reservoir of 1ml, suitable for powder, solution, suspension, particulates or mini-tablets.
Behind the drug reservoir is a spring with an antenna and a radiotracer port containing a gamma-emitting radionuclide to track the capsule location within the GI tract.
Drug delivery can be targeted by taking a drink containing a second gamma-emitting radionuclide, which provides an outline of the stomach and colon.
An activation unit sends an electromagnetic signal which is picked up by the antenna and activates the spring which pushes the drug out of the reservoir delivering it to a particular part of the GI tract.
Blood samples are then taken to determine the bioavailability of the drug at that location in the GI tract.
Most studies are designed to look at bioavailability at several areas of the GI tract.
"This will tell you what [modified release] strategy to go for and what technology is best for you," Jones said.
The technology also highlights whether there is a small window of absorption in particular areas and how feasible it would be to develop an oral modified release formulation, Jones said.
"This stops the risk and uncertainty in formulation development."
This is especially critical when studies by Pharmaceutical Profiles show about 60 per cent of drugs in development have a bioavailability profile which is difficult to develop a modified release formulation for.
Traditionally, intubation techniques have been used to assess regional drug absorption.
But these are invasive, involving the passage of a tube into the GI tract via the nose, mouth or rectum, causes discomfort, and are restricted to the use of solutions only.
According to Jones, the Enterion capsule had several advantages, besides helping with formulation development, including eliminating the need for animal models, time and cost savings by cutting out the "test-modify-test-modify" development pattern, and removing the need for guess work.
While the Enterion capsule has been around for several years, it is only recently that the company has really pushed the technology into the market place.
Pharmaceutical Profiles currently conduct about 40 clinical trials a year using the Enterion capsule.
