Drug Delivery and Formulation Testing

TNO | Knowledge for business

A quick, cost-efficient and reliable approach for pharmaceutical

research

TIM gastrointestinal models

TNOs patented in vitro gastrointestinal model TIM gives a quick insight into
the solubility, release and availability for absorption of pharmaceuticals
within the gastrointestinal tract. This well-validated and accurate system
has a much higher predictive value than regular dissolution tests. In
addition, it is a cost-efficient alternative for human and animal trials,
accelerating the process of product development.

in the model, including solubility, coating

stability, release profile, availability for
absorption, and drug-nutrient interactions.
With this information, one can make better
decisions on the selection of compounds
and/or formulations for further (in vivo)
studies and to define an optimal set-up for
clinical trials. By accelerating the process of
drug development, this may save a lot of
manpower and money.
TIM experiments are free from ethical
constraints: extensive admission procedures
are not necessary. One might work even with
(potential) toxic compounds or diseasecausing bacteria (under containment
conditions) without harming animals or
humans.

Accurate simulation
The computer-regulated gastrointestinal
model TIM accurately simulates the
conditions in the gastrointestinal tract. It
consists of several compartments,
interconnected by valves, and mimics the
bodys temperature and peristaltic
movements. Acidity and electrolyte
concentrations in the system are regulated,
as well as the swallowing of saliva, and the
secretion of gastric acid and enzymes,
pancreatic juice with enzymes, and bile salts.

The TIM-1 system represents the

gastrointestinal tract from stomach to small
intestine, while TIM-2 covers the large
intestine. Both models have been validated
in comparison to in vivo studies and have
been applied for a large number of drugs.
Cost-efficient
Saving time and money in combination with
a high predictive value for the in vivo
situation is one of TIMs main advantages. A
wide range of physico-chemical properties of
formulations and drugs can be investigated

Many applications
TIM enables a detailed analysis of the
release, solubility and bioaccessibility profile
as well as on other physico-chemical
properties or interactions of pharmaceuticals
during gastrointestinal passage. The model
can be adapted to a wide range of target
groups, such as babies, young adults, senior
people and patients with impaired
gastrointestinal conditions. It can be adapted
to animals as well, for example dogs.
For over fifteen years, the TIM systems have
been used successfully and study results
have been described in over 30 scientific,
peer-reviewed publications. Data from the
TIM systems have been accepted by several
local authorities, including the American
Food and Drugs Administration (FDA). A list
of (peer-reviewed) publications is available
on request.

Drug Delivery and Formulation testing

pharma37B/31-08-2009

A quick, cost-efficient and reliable approach for pharmaceutical research

TIM gastrointestinal models

TNO Quality of Life

Track record
Until now, in the TIM-1 system, TNO has
tested over 50 different compounds, most of
them under fasted state as well as under fed
state conditions, with or without an FDA
recommended high fat meal matrix. Most of
these tested compounds were poorly soluble,
while 70% was lipophilic. Divided over the
BCS class I + III and class II + IV the ratio
was approximately 3:7. The individual
compounds were formulated in two up to
twelve different drug-dosage forms. In a
number of cases the compounds or
formulations have been tested under specific
pathological gastrointestinal conditions.

Services
To profit from TIM, customers can choose
from two options:
Contract research: TNO performs
experiments according to a study plan
approved by the company;
Lease construction: the company rents a
TIM-1 system and performs its own inhouse experiments. TNO is responsible for
system installation and maintenance,
training, and advice on experimental setup.
Currently, in North-America and Europe,
about 20 TIM-1 systems are operational for
and at various companies and institutes.

TNO Quality of Life is a part of TNO; Europe's

In TIM-2, whether or not in combination

with TIM-1, we have tested over 15 different
compounds and formulations on
bioaccessibility from the colon and/or on
bioconversion to the activated form by the
colon microbiota. In 60% of these
experiments we have also investigated the
influence of drugs on the composition and
metabolic activity of the microbiota after
single or repeated dose.

TIM-1 and TIM-2 services can be combined

with other TNO expertise, including:
Cell cultures and intestinal segments, to
study (intestinal) cell transport,
metabolism and specific functions;
In silico modelling, to predict plasma levels
after single dosage or during long-term
oral intake;
Pharmaco-kinetic studies (ADME) and
pharmaco-dynamic studies.

Postal address

largest independent research institute for

technological and strategic research and
consultancy. By translating scientific
knowledge into practice we optimise the
innovative abilities of the industry and
government. As a research partner TNO works
for various industries worldwide.
Pharma office
Visiting address
Utrechtseweg 48
3704 HE Zeist
The Netherlands

P.O. Box 360

3700 AJ Zeist
The Netherlands
For more information, please contact us.
E info-pharma@tno.nl
The Netherlands, Zeist
P +31 30 694 47 41
F +31 30 694 48 45
The Netherlands, Leiden
P +31 71 518 14 99
F +31 71 518 19 01
North America
P +1 416 837 75 00
F +31 30 694 48 45
Japan
P +81 45 478 51 30
F +81 45 473 79 59
www.tno.nl/pharma
TNO | Knowledge for business

TIM-1

TIM-2