Project: Polymeric matrices for transdermal or epidermal drug delivery with optimized bioavailability and innovative release kinetics.

The ways in which chemicals or drugs are administered have gained much attention in the last decades. Transdermal drug delivery for treatments that require lower doses over prolonged time periods, have been developed as alternatives to oral, intravenous, intramuscular or subcutaneous drug administrations. Several drug and chemical delivery systems for transdermal and epidermal administration are known in the state-of-the-art and can be found in the market for human health and veterinary applications. These devices rely on two CO technologies for the storage and diffusion of active substances: reservoirs sealed by a liner, with or without porous membrane, and polymeric matrices. These technologies are applied to develop products such as transdermal patches and animals’ collars, ear tags._x000D__x000D_The efficacy of transdermal or epidermal administration is dependent upon the bioavailabity of the active substances and their release kinetics. Polymeric matrices are much suitable to obtain prolonged release kinetics. However their manufacturing processes, solvent dissolution and holt-melt, are much refutable in terms of sustainable development. Moreover they can alter the properties of the drugs, actives substances. The release mechanism for the polymeric matrix relies on an unsteady-state condition and a concentration dependent flux of liquid solution as described in Fick’s law. The current polymeric matrix technology is still very basic (COly PVC material with the addition of plasticizer) and has no control whatsoever on the release kinetics. Indeed, straight after manufacturing, the active substance starts diffusing from the higher to the lower concentration zone in the polymeric matrix, tends to accumulate at the surface and to even leach. To avoid such drawback, the matrix is sealed or surface treated. Moreover, the accumulation of the active substance near the surface generates an immediate high delivery of drug known as the “burst effect” which is not desirable for certain applications. Today, no polymeric matrix is capable to properly deliver active substance commercialy available in crystalline physical form that is hardly soluble. Such substances like pyrethroids used in parasite-repellent applications, are prepared under a liquid form loaded into the polymer matrix during manufacturing. The liquid composition diffuses into the matrix and loses its soluble form straight after liberation from the matrix. This results in a waste of substance (air and UV degradation) and a poor bioavailability (several days diffusion lag time in the skin). _x000D__x000D_The project will start from the advanced pre-existing know-how of the CO applicant relying on new approaches and concepts for the manufacturing of the polymeric matrices, without solvent and high temperature, and for the engineering of the matrices. The FIT-ON project will push knowledge well past current polymeric matrix technology to overcome the current technical barriers and develop new functions.The project will develop a new polymeric matrix model capable to optimize the bioavailability of the active substances and to control the delivery mechanism in order to provide customized innovative dynamic release profiles adapted to the needs of the customers._x000D__x000D_Transdermal drug delivery for human health when compared to other emerging modes of drug delivery is gaining rapid acceptance. Several transdermal products and applications include hormone replacement therapy with estradiol, management of pain with fentanyl, angina pectoris with nitroglycerin, smoking cessation with nicotine and neurological disorders with scopolamine. Yet, the pharmaceutical industry tends to view transdermal drug delivery as a limited technology. For veterinary applications, epidermal administration is well developed for the delivery of ectoparasiticides. Other fields of applications could be developed, notably for the delivery of drugs when oral administration poses gastric disturbances and/or other side effects. This is the case, for instance, for the delivery of methimazole for the treatment of hyperthyroidism in cats and the delivery of antidepressant amitriptyline (Elavil) to treat behavior problems and lower urinary tract diseases. Some of the medications like fentanyl for post-operative and chronic pain control in human are currently being used in veterinary hospitals for pain control on dogs, cats and horses. _x000D__x000D_The new polymeric matrix technology developed during the project will push forwards the current boundaries and will offer new perspectives for the development of transdermal and epidermal drug delivery for human health, care and veterinary applications. The consortium will be constituted by the CO applicant, an innovative SME, leader in the polymeric matrix technology, a product marketing and distribution company, leader in the veterinary market, and a research laboratory which will perform key R&D tasks for the technological developments. _x000D_

Acronym FIT-ON (Reference Number: 5229)
Duration 01/01/2010 - 30/06/2012
Project Topic The efficacy of transdermal drug delivery systems is dependent upon the bioavailabity of the active substances and their release kinetics. The project will develop polymeric matrix models capable to optimize the diffusion of the active substances and to provide innovative dynamic release profiles.
Project Results
(after finalisation)
We developed an insecticide device for dogs containing Deltamethrin with a release kinetic which is significantly improved because we formulated the active molecule with suitable co-carriers which limit its crystalline form. We chose a specific shape of device called Fit-on which is convenient for a majority of collars without removing the collar to fix the device. The first vivo tests on dogs showed that the release of Deltamethrin in real conditions was undersized so that the efficacy was not regular enough. Taking into account the know-how we have acquired during the project, we focused on one of the two polymers originally screened and added a third carrier able to better compatibilize Deltamethrin lipophilic composition with polymer matrix. We developed a complementary vitro test where we measure mechanical release by contact because we found it more correlated to real behaviour on dogs; with that tools, we found a release at least similar than competitor collar Scalibor indeed a little bit higher, which is in favour of a more consistent performance. We are now assessing with P Vetpharma what will be the new process to register the new grade of Fit-on and what is the complementary work to lead.
Network Eurostars
Call Eurostars Cut-Off 3

Project partner

Number Name Role Country
3 Vetpharma Animal Health, S.L. Partner Spain
3 Institut National Polytechnique de Toulouse Partner France
3 AB7 Industries Coordinator France