Gastrointestinal Behavior of Posaconazol in Healthy Volunteers
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
The aim of this study is to understand the behavior of posaconazol gives as a suspension and
solution in the gastrointestinal tract in human volunteers. The investigators know that
supersaturation for this compound can be achieved by the influence of the gastrointestinal
tract: The acid environment of the stomach creates a optimized environment for the basic
compound to reach a high solubility, while the neutral environment of the small intestine
creates a low solubility environment for the compound. The transit from stomach to small
intestine gives the opportunity for the drug to create a supersaturated solution. Giving the
drug as a solution to the healthy volunteer makes sure that precipitation is not occurring in
the stomach and that precipitation has to happen in the small intestine. After all,
supersaturation is a state that is not thermodynamic stable and always will want to
precipitate. Giving the drug as a suspension to the healthy volunteers, can make it possible
that still some particles of the drug are not in dissolution and that those particles will
flow to the small intestine where other particles easily can bind to. This will make that
almost the whole supersaturated solution is immediately precipitated.
The investigators want to give the suspension by the authorized drug called Noxafil. On the
other hand an aqueous solution will be made by adjusting the pH to 1.2 (which is conform with
the pH of the stomach) and given to the volunteers by the stomach catheter. This 2
formulations will be tested in a fasted state and a fed state (by giving 2 Ensure plus shakes
to the volunteers before the experiment starts). After intake of the formulation, gastric and
duodenal fluids will be aspirated by the catheters and analyzed at their laboratory. So the
four conditions the investigators want to study are:
1. 10 mL Suspension of posaconazol (Noxafil 40mg/mL) together with a glass of 240 mL water
in a fasted state
2. 250 mL solution of posaconazol, by dissolving 2.6 mL autohorized suspension (Noxafil) in
247 mL water, adjusted to pH 1.2 by hydrochloric acid given to the volunteer in a fasted
state.
3. 10 mL Suspension of posaconazol (Noxafil 40mg/mL) together with a glass of 240 mL water
in a fed state (by giving 20 minute before intake of the formulation, 2 ensure plus
shakes)
4. 250 mL solution of posaconazol, by dissolving 2.6 mL autohorized suspension (Noxafil) in
247 mL water, adjusted to pH 1.2 by hydrochloric acid given to the volunteer in a fed
state (by giving 20 minute before intake of the formulation, 2 ensure plus shakes).
By getting more knowledge about the behavior of posaconazol (interplay supersaturation /
precipitation) more insights can be achieved for the development of supersaturating drug
delivery systems.