Accurate simulationThe 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-efficientSaving 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

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 disease-

causing bacteria (under containment

conditions) without harming animals or

humans.

Many applicationsTIM 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.

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

TNO | Knowledge for business

A quick, cost-efficient and reliable approach for pharmaceuticalresearch

TIM gastrointestinal models

Drug Delivery and Formulation Testing

Drug Delivery and Formulation testing

A quick, cost-efficient and reliable approach for pharmaceutical researchTIM gastrointestinal models

TNO Quality of Life

pharma37B/31-08-2009

Track recordUntil 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.

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.

ServicesTo 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 in-

house experiments. TNO is responsible for

system installation and maintenance,

training, and advice on experimental set-

up.

Currently, in North-America and Europe,

about 20 TIM-1 systems are operational for

and at various companies and institutes.

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.

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

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

Postal address

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-2TIM-1