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

Abstract

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°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.

Key Words:

• Charcoal
• Excipients
• Intratumoral
• Mammary tumors
• Suspension