Monique Seiller

Cyclodextrins and emulsions.

This paper synthesises the literature on interactions between cyclodextrins (CD) and fatty acids and glycerides, and explains how these interactions allow the use of cyclodextrins to stabilise emulsions. An example of formulation with cyclodextrins is given which discusses the preparation of simple o/w emulsions, the addition of a model active ingredient, and the preparation of multiple emulsions in the absence of preformed surface active agents.

Interactions of a non-ionic ABA copolymer surfactant with phospholipid monolayers: Possible relevance to emulsion stabilization

Abstract The π - A isotherms of phospholipid monolayers in the presence of ABA polyoxyethylene, polyoxypropylene block copolymer (poloxamer) in the aqueous subphase exhibit a marked increase in surface pressure, indicating that poloxamer molecules are localized at the air-water interface and are intercalated between phospholipid molecules. While the surface pressure at collapse remained practically constant at poloxamer concentrations lower than the CMC, it increased at poloxamer concentrations above the CMC. The molecular area values were independent of poloxamer concentration. These results suggest that ejection of poloxamer molecules from phospholipid monolayers takes place at high compressions. In independent studies on the stability of emulsions using the same phospholipid-poloxamer combination, it was noted that an optimal concentration of these emulsifiers was necessary to stabilize the emulsion. The emulsion stability data which corroborate the results of surface pressure measurements confirm the existence of an association between poloxamer and phospholipid molecules. At poloxamer concentrations slightly higher than the CMC, poloxamer aggregates appear to form a hydrophilic environment close to the dispersed oily droplets, thus favoring emulsion stabilization. A model of molecular arrangements at the mixed monolayer-water interface is proposed.

Effect of camphor/cyclodextrin complexation on the stability of O/W/O multiple emulsions.

Camphor (CA) encapsulation in oil/water/oil multiple emulsions prepared with cyclodextrin disturbs the emulsifier potential of alpha- and beta-natural cyclodextrins (CD). It was suggested that the size and geometrical fit between the CD cavity and CA could induce CD/CA complex formation in place of emulsifier formation leading to perturbation of emulsion stability. The complexation between CA and alpha-, beta- or gamma-CD in solution in the presence of oil phase are confirmed by phase-solubility diagrams, circular dichroism and 1H NMR. Furthermore, in order to mimic the emulsion system, CD/CA/soybean oil ternary dispersions were prepared to observe the complexation behavior of alpha-, beta- or gamma-CD/CA by circular dichroism. X-ray diffraction on emulsion samples prepared with alpha- and beta-CD confirms that the precipitates observed in emulsions are probably composed of crystals of CD/CA complexes. A preliminary study of the interaction between drug and CD before the formulation seems indispensable to prevent the risk of incompatibility.

Stability Study of W/O/W Viscosified Multiple Emulsions

Stable multiple emulsions with a small proportion of primary emulsion containing different viscosifying agents in the outer aqueous phase were formulated. The multiple systems were assessed by evaluating several parameters, such as the macroscopic aspect, droplet size, release rate, and accelerated stability under elevated temperatures. The effect of different viscosifying agents at different concentrations on the stability and the multiplicity of the multiple emulsions was examined. The viscosity increased by increasing the concentration of the viscosifying agents. It also appeared that the viscosifying agents increased the temperature stability of the multiple emulsions. As a result, the formulation viscosified with Klucel was more stable, while the one prepared with carbomer viscosified the outer phase at much lower concentrations with much better skin feel.

Presurgery labelling of breast tumours with a charcoal suspension for intratumour injection

Objectives. A main goal of neoadjuvant chemotherapy (CT) in locally advanced breast carcinomas (clinical size >3 cm) is to decrease the tumour volume to permit conservative surgery. In about 10% of the cases, the tumour nodule is not clinically palpable after CT and it is necessary to tattoo the initial site in order to guide the surgeon for the resection of any residual tumour. We have developed a charcoal suspension for injection into human breast tumours. The aim is to enable the pathologist to guide the surgeon during excision of the residual tumour, which is not otherwise visible, after CT. Pharmacological and toxicological studies in animals have indicated that the suspension is well tolerated. Methods. We investigated the efficacy and tolerability of a charcoal suspension in a group of eight patients with a palpable breast tumour of clinical size 1.5-4 cm, which was removed 24 hours to 4 days after the injection of 1 mL of 4% charcoal suspension into the tumour. Results. This preliminary clinical study shows that the injection of charcoal is well tolerated by patients and is a good method of tattooing tumour. The charcoal was seen in or at the periphery of the nodule in the surgical specimen. No inflammatory reaction or diffusion was observed. Conclusions. Based on these results, this suspension appears suitable for tattooing breast carcinomas over a period of 3 months for patients programmed to receive preoperative CT.

Formulation of a Charcoal Suspension for Intratumoral Injection. Study of Galenical Excipients

To tattoo human breast cancer prior to chemotherapy, radiotherapy, or surgery, thus allowing a better localization of the remaining tumor by the surgeon, we developed a formulation containing 10% charcoal suspended in water for parenteral preparations. The present study concerns a new step in the development of the charcoal suspension. We sought to determine whether the addition of various excipients could improve the formulation properties and affect the labeling of tumor by the suspension. We have tested surfactants (egg lecithin, polysorbate 80, Cremophor EL, and Pluronic F68), isotonisants (sugars such as glucose and mannitol), polysaccharides (dextrans 20 and 40), and Cabosil, a pyrogenated silica. Except for glucose and mannitol, which were added at a 5% concentration, the other excipients were added at a 0.1% concentration, they were dissolved in water for parenteral injection and sterilized at 120 degrees C for 20 min. We then measured diffusion in vivo in mammary tumor. In vivo, when injected intratumorally in mice, a greater diffusion of charcoal particles was noted within the tumor (in the case of egg lecithin, polysorbate 80, dextran 20 and 40, and glucose) and sometimes in some organs (e.g., Cremophor EL and mannitol). Pluronic F68 slightly improved the stability of the suspension and did not lead to marked diffusion at the injection site, but it showed slight toxicity and cannot be used in the formulation. We concluded that the best formulation was an aqueous 10% micronized peat charcoal suspension.

Viscoelastic properties of paracrystalline phases appearing in water-surface agent-oil diagrams.

The ternary mixtures investigated were obtained from water, mineral oil and ether‐linked non‐ionic surfactants (polyoxyethylene derivatives of oleic alcohol). The examination of the rheological properties of these mixtures, particularly the viscoelastic properties of the various phases encountered in these diagrams, was expanded. The phases examined were: