Propofol for migraine

Purpose and goal

The purpose of the project was threefold: 1) To establish what regulatory requirememnts would be placed on a unique formulation of propofol such as this, 2) To evaluate the feasibility of formulating and scaling up for GMP manufacture such a propofol formulation and 3) To test the resulting formulation at the agreed strength for the agreed time to allow the most flexible clinical programme possible. Goals 1 and 2 have been met, but time and expense overruns have prevented the third goal from being achieved yet.

Results and expected effects

The results of the project were that the interactions with the regulatory authorities gave a very clear picture of the regulatory requirements that would be placed on a new formulation of propofol for the treatment of migraine. As expected, local toleration studies in a mutually agreed species will be required to assure no local toxic reactions occur in the buccal mucosa upon repeated dosing of propofol in the film. Formulation work focussed on assuring a uniform propofol dispersion in the alginate film and several additives/excipients were tried before the most favorable one was found.

Approach and implementation

The first regulatory interaction (Singapore) took place before the project officially started, but that interaction and that with the UK MHRA gave roughly the same answer to our questions. This part of the project went as expected. The formulation work went much more slowly due to the experimentation with different formulations without the ability to generate data on in vivo uptake. This aspect, along with queing for a place on the manufacturing equipment meant that this aspect both both more expensive and more time consuming, making it impossible to start toleration studies yet.