Frédéric Eeckman

Effect of some physiological and non-physiological compounds on the phase transition temperature of thermoresponsive polymers intended for oral controlled-drug delivery

Poly-N-isopropylacrylamide (PNIPAAm) thermosensibility makes this polymer a very attractive candidate for controlled drug delivery systems. The polymer possesses a lower critical solution temperature (LCST) which was found to be around 32 degrees C in pure water, but which can be affected by the medium composition, i.e. presence of salts or surfactants. The knowledge of the effects of such substances on the LCST is very important while using PNIPAAm as a controlled drug delivery agent. The influence of a number of physiological and non-physiological salts and surfactants has been studied. The results obtained show that the addition of salts provokes an important decrease of the LCST of the polymer (salting out effect). A strong influence of the valence and of the size of the anions of the halide group was found. As to the surfactants, according to their type and concentration, a decrease or an increase of the LCST or even no effect at all were found. The effect of the GI secretions on the PNIPAAm phase separation temperature is also discussed.

Evaluation of a new controlled-drug delivery concept based on the use of thermoresponsive polymers.

The purpose of this work is to develop a new delivery concept making a thermosensitive polymer based on poly(N-isopropylacrylamide) (PNIPAAm) useful as a time-controlled drug release device, without any temperature changes of the dissolution medium. It was previously found that some salts induce a decrease of the polymer lower critical solution temperature (LCST). Use is here made of that property to show that salt concentration variations can be used as a substitute for temperature changes to make the polymer coating of compression-coated tablets soluble or insoluble, consequently creating a possible new concept of drug delivery control from delivery systems containing thermoresponsive polymers. The obtained results show the influence of the type and amount of salts incorporated into compression-coated tablets on the release lag time of a model drug.

Surfactant induced drug delivery based on the use of thermosensitive polymers.

A novel approach of controlled drug delivery using thermosensitive polymers is developed in this paper. The drug release occurs at physiological temperature, at which the polymer is normally not soluble, and no medium temperature changes are required to bring about the delivery. For this purpose benefit is taken from the specific binding properties of some anionic surfactants and poly(N-isopropylacrylamide) (PNIPAAm) in order to modify the dissolution properties of PNIPAAm and of a copolymer with N-vinyl-acetamide (NVA), and so to induce the release of a drug contained in compression coated tablets. The influence of surfactant type and amount on the drug release rates and lag times from tablets coated with PNIPAAm or with the copolymer are discussed. It was found that the lag time is influenced by the surfactant species and amount. When use is made of a copolymer as coating agent, it is possible to bring about the release of the drug by incorporating only a very small amount (as low as 2%) of sodium dodecyl sulfate (SDS) in the coating.