Structural and rheological properties of chitosan semi-interpenetrated networks.

The local structure and the viscoelastic properties of semi-interpenetrated biopolymer networks based on cross-linked chitosan and poly(ethylene oxide) (PEO) were investigated by Small Angle Neutron Scattering and rheological measurements. The specific viscosity and the entanglement concentration of chitosan were first determined, respectively, by capillary viscosimetry and steady-state shear rheology experiments performed at different polymer concentrations. Mechanical spectroscopy was then used to study the gelation process of chitosan/PEO semi-interpenetrated networks. By fitting the frequency dependence of the elastic and loss moduli with extended relations of relaxation shear modulus around the sol-gel transition, it was shown that the addition of PEO chains had a significant effect on the viscoelastic properties of aqueous chitosan networks but no effect on the gelation time. The improvement of mechanical properties was in accordance with the correlation length decrease deduced from Small Angle Neutron Scattering experiments.

[Interactions between cyclodextrins and triglycerides: from emulsion stabilisation to the emergence of a new drug delivery system called "beads"]. / Interactions entre les cyclodextrines et les triglycérides : de la stabilisation des émulsions à l'obtention d'un nouveau système galénique appelé << billes >>.

Natural cyclodextrins are cyclic oligosaccharides which can be modified to obtain more water soluble or insoluble derivatives. The main interest of cyclodextrins results from their ability to form an inclusion complex with hydrophobic molecules. Inclusion constitutes a true molecular encapsulation. This property is employed in pharmaceutical industry to facilitate the formulation of poorly water soluble and/or fragile drugs. A more recent application of cyclodextrins consists in their use in the preparation of dispersed systems such as micro- and nanoparticles or even liposomes. When incorporated in dispersed systems, cyclodextrin can enhance drug solubility, drug stability and drug loading. Interestingly, cyclodextrins themselves can also be employed to form or stabilise dispersed systems (material or emulsifying agent). For example, the interactions between cyclodextrins with components of the vegetable oils (more especially with triglycerides) allow to stabilise simple or multiple emulsions but also to form particles called "beads". Very rich in oil, this novel lipid carrier presents an important potential for the encapsulation of highly lipophilic compounds and their delivery by topical and oral routes. These two applications are more particularly developed in the present paper.

Formulation and characterisation of beads prepared from natural cyclodextrins and vegetable, mineral or synthetic oils.

A continuous external shaking for 2.5 days of a mixture composed of alpha-cyclodextrin (6%), soybean oil (19.6%) and water (74.4%) resulted in a calibrated lipid carrier namely bead with a high fabrication yield. The purpose of this work was to explore the possibility to substitute alpha-cyclodextrin by other natural cyclodextrins, i.e. beta- and gamma-cyclodextrin and then soybean oil by mineral (Primol) 352 and Marcol 82) or synthetic (Silicon 200) fluid 10, 50 or 100cSt) oils. Beads can be successfully prepared using Marcol 82 with alpha-cyclodextrin and Silicon 50 or 100cSt with gamma-cyclodextrin. The area inside oil/cyclodextrin/water ternary diagram corresponding to bead occurrence was superior for the Marcol 82/alpha-cyclodextrin couple compared to that observed with soybean oil/alpha-cyclodextrin couple. Only a few ratios of Silicon 50 and 100cSt/gamma-cyclodextrin/water led to beads. The combinations which did not induce bead occurrence gave either emulsions, two non-miscible liquids or a solid mixture. Whatever the materials used, beads exhibited similarities: presence of a crystalline organisation and viscoelastic properties. Manufacturing process of paraffin- and silicon-based beads need further optimisation to increase fabrication yield and later on, to take advantages from the high stability of both oils for the formulation of drugs with beads.

Assessment of oil polarity: comparison of evaluation methods.

In multiple emulsion systems, oily or aqueous transfers may occur between the dispersed droplets through the continuous phase. These transfers are controlled by both the surfactant system (micellar transport), and the partial solubility of one phase in another (molecular transport). The latter could be anticipated from the knowledge of oil polarity, if this information could easily be obtained. In this work, the relative polarity of eight oils used for various purposes has been evaluated from the comparison of their dielectric requirement for solubilization, their interfacial tension and chromatographic analysis. The results showed the complementarities of HPLC analysis and interfacial tension measurements and their superiority over the solubilization method for classifying oils as a function of their polarity.

A very promising new glucolipidic surfactant: Lipowheat.

Lipowheat is an entirely biodegradable 100% natural active ingredient, extracted from non-transgenic wheat. Thanks to its very interesting properties, it can integrate the composition of most cosmetic and pharmaceutical products. The aim of this work was first to realize a large range of stable simple or multiple emulsions, in order to determine and evaluate the ability of a new glucolipidic surfactant Lipowheat to form and stabilize emulsions. The rheological properties of these emulsions were tested during a 30-day storage period at three different storage conditions (cold, room temperature and at 40 degrees C). In addition to dynamic and static rheological tests, droplet size distribution of the cream was also determined. Furthermore, a stable simple emulsion was selected to realize percutaneous absorption and evaluate the properties of Lipowheat.

Release of antiseptics from the aqueous compartments of a w/o/w multiple emulsion.

A w/o/w multiple emulsion drug carrier system has been developed for local vaginal therapy. To improve its efficacy and to extend the antimicrobial spectrum activity of benzalkonium chloride (CBZ), which is introduced in the external aqueous phase, chlorhexidine digluconate (CHD) was added to the internal aqueous phase of the multiple emulsions. The minimal bactericidal concentrations (MBC) for the association of CHD and CBZ in emulsion were determined towards Escherichia coli and Staphylococcus aureus. The main release mechanism considered for the CHD encapsulated in the inner phase was a swelling-breakdown phenomenon which followed dilution of the emulsion under hypo-osmotic conditions. In order to demonstrate this release, the bactericidal effect of multiple emulsions undiluted and diluted 1-5 and 1-10 in hypo-osmotic conditions at two CHD concentrations was evaluated. To validate and quantify this release, rheological and release kinetics studies were used. The bactericidal activity of combination CBZ-CHD in the emulsion was synergistic on the two bacterial strains and the release of encapsulated CHD in the internal phase was obtained following its dilution in hypo-osmotic conditions. Vaginal administration could be carried out following dilution at 1-5 in sterile water for multiple emulsions containing the lower concentration of CHD.

Physicochemical characterization and in vitro release of salicylic acid from O/W emulsions prepared with Montanov 68: effect of formulation parameters.

Montanovs are surfactants consisting of a combination of alkylpolyglucosides and long chain saturated alcohols. They are used to formulated oil in water (O/W) emulsions where they generate liquid crystals. Emulsions containing 5% Montanov 68 with 40% Lanol 1688 were prepared and salicylic acid (SA) was incorporated at different stages of the O/W emulsion preparation. This study highlights the effects of formulation parameters on the microscopic characteristics, particle size and rheologic properties of Montanov 68 O/W emulsions. Diffusion studies with these emulsions showed the influence of SA incorporation at different steps on the release kinetics. Montanov enabled the release of SA to be controlled when it was solubilized in the internal phase. The presence of a physical barrier formed by the Montanov at the interface between the oil and water appeared to modulate the SA passage to the external phase.

W/O/W Multiple Emulsions Submitted to a Linear Shear Flow: Correlation between Fragmentation and Release.

The present work attempted to apply the theoretical framework described by Taylor to different multiple emulsions under shear. The results were in relatively good agreement with the theory. The correlation between the fragmentation and release studies was well proved. Moreover, these studies showed that mechanisms taking place during the breakup were complex and did not always lead to a total release of the entrapped electrolyte. Some phenomena such as a partial leakage of the internal aqueous compartment or the expulsion of aqueous microglobules covered by a residual lipophilic film were able to restrict the release. Copyright 1999 Academic Press.