Project: ALZHEIMER Transdermal Therapeutic Systems

_x000D_The goal of this project is to develop a transdermal therapeutic system (TTS) by implementing a rate-controlled systemic drug delivery mechanism to enable significant improvement in the individual medication of Alzheimer patients. _x000D__x000D_This approach allows a minimization of the drug dose while COtaining the therapeutic efficiency, leading to less physical strain and less side effects in patients. On the other hand, it complements favourably the use of drug combinations that will be used more and more to treat Alzheimer’s patients as this technology allows to overcome the drawbacks of multiple pharmacokinetics and ADME (adsorption, distribution, metabolism and excretion) parameters._x000D__x000D_This project proposal involves a multi-disciplinary approach, using suitable linker chemistry combined with pharmaceutical engineering enabling the rate-controlled drug release. It involves the development of adapted polymer waveguides, a control unit implemented in the TTS and a wireless data transfer module for individual programming of the TTS by the doctor or clinician. _x000D__x000D_From the pharmaceutical - drug discovery prospective, this project proposal involve the search for optimal synergistic drug combinations. _x000D__x000D_The ALTHERAS idea and project started with the needs of two companies: Rhenovia Pharma SAS (France) and Portmann instruments AG (Switzerland). Rhenovia Pharma, a French start up founded in 2007, has defined and is now developing a Bio informatics platform to identify optimal synergistic drug combinations for central nervous system diseases. _x000D__x000D_To fill the gap from an idea to a product used for medication, the companies needs complementary know-how and technologies, especially to have synergistic vectors to combine drugs for the treatment of Alzheimer. _x000D__x000D_Portmann, a Swiss SME with 25 years of experience in the field of scientific instrumentation needs to develop new technologies to expand. The company will bring into the project a comprehensive knowledge and know how on key issues as chemical binding, fluorescence measurement technologies and conception and fabrication of medical devices. _x000D__x000D_Developed products in the frame of the ALTHERAS project will in the foreseeable future provide to both companies a high return on investments either by direct exploitation of the products for Alzheimer application or by selling licences for other fields of application than Alzheimer diseases._x000D__x000D__x000D__x000D__x000D__x000D_

Acronym	ALTHERAS (Reference Number: 4349)
Duration	02/06/2008 - 02/06/2011
Project Topic	The objective of this project is to develop a transdermal therapeutic system (TTS) by implementing a rate-controlled systemic drug delivery mechanism to enable significant improvement in the individual medication of Alzheimer patients.
Project Results (after finalisation)	The results of our project are in accordance with the project planning ( as outlined in the milestones and deliverables of the project application). All WP's and deliverables were realized as planned. All the financials issues are in accordance with the planned Altheras program. In the last phase of the project, impressive technical progress were achieved to establish the proof of concept for obtaining a drug loaded porous matrix and the release of this drug through human skin (Transdermal study). The work and the progress realized during this technical progress phase can be divided into four CO activities: • Chemistry studies • ChipM production(Chitosan porous Matrix) • Transdermal studies • Proposals for patch manufacturing and its uses. Considering the excellent results we obtained, we conclude that the proof of concept has been established for the Eurostars Patch, thereby successfully terminating the contract and resolving the initial challenges. We are now able to propose a full process for the production of a modified matrix, which makes possible the release of a drug by controlled UV illumination. This process has been worked out without any difficult technologies and all the quantitative analyses, except for the ChipM microscopic study, can be performed by HPLC of UV-Visible spectrometry, which makes them suitable for industrial applications. Regarding the chemical part of the process, which includes the synthesis of the photolinker and the coupling steps, a very good yield has been reached for the production of the photolinker and the coupling steps. The major part consisted to obtain a porous matrix with an isotropic pore distribution and also a good reproducibility. The invented POMAP(POrous MAtrix Producer) apparatus is in production to precisely control thermal exchanges, as they directly impact the properties of the produced ChipM (Chitosan porous matrices). The created POMAP has been designed specially by Portmann Instruments for the production of porous materials by a freeze gelation method. Other methods have been tested, including freezing at constant temperature (-20 °C) or with liquid nitrogen (- 196°C), but in both cases the results were unsatisfactory. The advantages of the POMAP are: • Control of the cooling speed, which influences pore size of the material. • Fast and adaptive control of the temperature. • Easy production of matrices with good reproducibility and isotropy. • Simple process, with possibility of scale-up Basically, the POMAP is constituted of 4 CO parts. For the production of porous materials by phase separation, the control of the temperature and especially of the cooling rate has an important influence on the final properties of the materials: mean pore size, specific surface and porosity. The POMAP is designed to assure a precise control of these parameters. The transdermal study was an important step to get the proof of concept and this aspect of the project can now be considered as a complete success. The quality of the results could be ( and will be)improved by optimization of the process, but the results are considered as satisfactory enough for the proof of concept. Finally concerning the assembling of the drug-loaded matrix with the electronic part of the patch, several solutions are presented in the final report. The reduction of the electronic component and its optimization are in progress and different options are investigated for the power supply, the UV emission and the programming. For the programming, a solution is presented in the final report. Briefly, a complete transdermal study should give enough information for a 3D data fit. Then, a program should be able to adapt the time of illumination of the patch as a function of the drug amount already released and the amount of drug to be release.
Network	Eurostars
Call	Eurostars Cut-Off 1

Project partner

Number	Name	Role	Country
2	Portmann Instruments	Partner	Switzerland
2	RHENOVIA PHARMA	Coordinator	France