Micro/nanonisation du naproxene et du dipropionate debeclom ethasone en milieu aqueux par fragmentation laser femtosecond

Reducing the particle size of drugs is a simple approach that may be used to improve their bioavailability, especially for compounds delivered by inhalation and orally. However, current micro/nanonization techniques are not well adapted to the drug discovery stage, where the availability of the actives is scarce. We propose a novel approach, laser fragmentation, to perform micro/nanonization of drugs using small quantities. Our hypothesis is that the laser process can produce micro/nanocrystals of two drug models, beclomethasone dipropionate (BDP) (pulmonary drug) and naproxen (oral drug), with minimal physico-chemical transformations.;Laser fragmentation consists in focusing a laser radiation into a magnetically agitated drug suspension. In this study, a femtosecond laser was used. The drugs particle size was characterized by dynamic light scattering and scanning electron microscopy. The degradation was evaluated by high performance liquid chromatography. The physicochemical properties of the lyophilized micro/nanocrystals were evaluated by Fourier transform infrared spectroscopy, x-ray diffraction, elemental analysis and differential scanning calorimetry. The in vitro dissolution kinetics of nanoparticles was also studied.;Nanocrystals of naproxen and microcrystals of BDP were successfully produced by laser fragmentation. Particles of different sizes (from 500 nm to several micrometers) could be obtained by adjusting the process parameters. Nanonization was accompanied by 2 ∼ 3 times more chemical degradation than micronization. After the laser process, the chemical composition was mainly conserved (65% ∼ 100%), and the change may be attributed to a moderate oxidation occured during laser-drug interaction in water. Drug crystallinity was maintained, but an amorphous form may appear (possibly on the particle surface). The in vitro dissolution rate of laser-nanonized naproxen showed considerable improvements (at least 10 times faster) compared to the untreated drug powder.;Laser fragmentation enables the micronization of small quantities of drugs with limited degradation and polymorphic transformation. The nanonization presents more degradation and physico-chemical transformations. The process therefore represents a suitable micronization (and in some cases nanonization) technique for the drug discovery phase, and is of particular interest for poorly water-soluble pulmonary drugs.