Guy Broze

Investigation of a suitable in vitro dissolution test for itraconazole-based solid dispersions.

The difficulty to find a relevant in vitro dissolution test to evaluate poorly soluble drugs is a well-known issue. One way to enhance their aqueous solubility is to formulate them as amorphous solid dispersions. In this study, three formulations containing itraconazole (ITZ), a model drug, were tested in seven different conditions (different USP apparatuses and different media). Two of the formulations were amorphous solid dispersions namely Sporanox®, the marketed product, and extrudates composed of Soluplus® and ITZ produced by hot melt extrusion; and the last one was pure crystalline ITZ capsules. After each test, a ranking of the formulations was established. Surprisingly, the two amorphous solid dispersions exhibited very different behavior depending primarily on the dissolution media. Indeed, the extrudates showed a better release profile than Sporanox® in non-sink and in biphasic conditions, whilst Sporanox® showed a higher release profile than the extrudates in sink and fasted simulated gastric conditions. The disintegration, dynamic light scattering and nuclear magnetic resonance results highlighted the presence of interaction between the surfactants and Soluplus®, which slowed down the erosion of the polymer matrix. Indeed, the negative charge of sodium dodecyl sulfate (SDS) and bile salts interacted with the surface of the extrudates that formed a barrier through which the water hardly diffused. Moreover, Soluplus® and SDS formed mixed micelles in solution in which ITZ interacts with SDS, but no longer with Soluplus®. Regarding the biphasic dissolution test, the interactions between the octanol dissolved in the aqueous media disrupted the polymer--ITZ system leading to a reduced release of ITZ from Sporanox®, whilst it had no influence on the extrudates. All together these results pointed out the difficulty of finding a suitable in vitro dissolution test due to interactions between the excipients that complicates the prediction of the behavior of these solid dispersions in vivo.

Block, random and palm-tree amphiphilic fluorinated copolymers: controlled synthesis, surface activity and use as dispersion polymerization stabilizers

A series of novel fluorinated amphiphilic stabilizers of different architectures (diblock, grafted, or palm tree copolymers) were successfully prepared by reversible addition–fragmentation chain transfer. The surfactant properties of these copolymers were first evidenced by measuring the interfacial tension at the H2O/trifluorotoluene (TFT) interface, and the results were correlated with their stabilizing efficiency in the dispersion polymerization of 2-hydroxyethyl methacrylate (HEMA) in trifluorotoluene. The effects of the architecture and concentration of the stabilizer on the morphology, size and stability of the obtained polyHEMA particles were investigated. Whatever the architecture of the stabilizer, conditions could be adapted to produce submicronic spherical poly(HEMA) particles with diameters around 300 nm and a quite narrow size distribution.

Enzymatic synthesis and surface active properties of novel hemifluorinated mannose esters.

The lipase-catalysed esterification of sugars with hemifluorinated acid derivatives is reported for the first time. A series of mannose modified derivatives having fluorinated chains with different length have been prepared accordingly in moderate yield. A preliminary evaluation of the surface active properties of these hemifluorinated mannose esters revealed their ability to reduce the surface tension of water much more efficiently than their aliphatic counterparts.

Lipase catalysis and thiol-Michael addition: a relevant association for the synthesis of new surface active carbohydrate esters

A novel class of surface-active carbohydrate esters is prepared by a two-step strategy that takes advantage of the selectivity of enzymatic catalysis and the versatility of the thiol-Michael addition reaction. The surfactant performance of the produced aliphatic, fluorinated and silicon based sugar esters are evaluated by surface tension measurements. The novel thiolated mannose, made available in this work, appears as a powerful building block for the incorporation of unprotected sugar moieties into complex molecules.

Foamability and structure analysis of foams in Hele-Shaw cell

The authors have generated two-dimensional foams by imposing an intermittent drainage in a Hele-Shaw cell partially filled with a detergent/water mixture. The foam generation associated with this process is reproducible and depends on the surfactant molecules composing the solution. A kinetic model can be proposed for the foam evolution. The structure of the foam is also investigated: the average bubble side number and correlation functions are measured. Distinguishable behaviors are observed for different surfactant molecules. This way of producing a foam is thus adequate for applied foam structure characterizations and fundamental studies.

Synthesis and tensioactive properties of PEO-b-polyphosphate copolymers

Poly(ethylene oxide) (PEO)-b-polyphosphate copolymers made of hydrophilic PEO and hydrophobic polyphosphates are amphiphilic copolymers prone to self-assemble in water into nanoparticles. In this work, nanoparticles are obtained by the self-assembly of PEO-b-polyphosphate copolymers in water in the absence of any organic co-solvent whatever the length of the pendant alkyl chain (between 4 and 7 carbon atoms) of the polyphosphate block. Remarkably, this solvent-free process remains efficient even for the most hydrophobic polyphosphate blocks. The critical aggregation concentration (CAC) of the block copolymers was determined by pyrene probe fluorescence. Finally, the efficiency of these copolymer surfactants to decrease the air–water interface was measured by air-bubble tensiometry.

Experimental Study of the Rheological Properties of Ion Containing Amorphous Polymers

During the two last decades, the interest in block and graft copolymers has been largely increasing. As the chemical blocks linked together are thermodynamically uncompatible they form heterophase systems with specific properties of each block. A typical example of such a compound is the poly(styrene-b-butadiene-b-styrene). In this block copolymer, the hight Tg sequence (poly styrene) acts as a physical thermoreversible reticulation. Such compourris recieved the name of “thermoplastic elastomers” and promoted industrial applications.