Paclitaxel Solubility in Aqueous Dispersions and Mixed Micellar Solutions of Lecithin

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The aim of this study was to find a biocompatible, lecithin-based carrier for paclitaxel (PTX) suitable for intravenous infusion and ensuring a soluble PTX concentration of 100mg/100ml or higher for at least 24h. Aqueous dispersions of egg or soya lecithin (water-lecithin dispersions, WLD), mixed micellar (MM) solutions of egg lecithin and sodium deoxycholate, and formulations containing lecithin plus the co-surfactants and co-solvents poloxamer, polysorbate, Span, benzalkonium chloride, and macrogol were investigated. Amorphous PTX was prepared by lyophilization. PTX co-lyophilized with surfactants was also studied. Unlike crystalline PTX, the drug in an amorphous form is easily soluble in 1-5%(w/w) WLD or in MM. The highest solubility (up to 570mg/100ml) was achieved in 5% WLD. Dissolved PTX precipitated from all tested formulations over 24h. Despite this, concentrations of dissolved PTX of 100mg/100ml or higher were observed after 24h in 5% egg WLD, 1-5% soya WLD, and in 5%MM (lecithin : deoxycholate ratio 1: 1w/w). When four different batches of 5% egg WLD were prepared, containing PTX in clinically relevant concentration of 100mg/100ml, no precipitation of PTX was observed within 24h and this formulation is the most promising candidate for further in vivo studies. Neither additional surfactants nor co-lyophilization increased PTX solubility in the lecithin-based carriers. The use of parenteral emulsions as solvents for the co-lyophilized PTX also failed to increase the solubility of the drug up to the target concentration.
公益社団法人日本薬学会の論文
2008-01-01

Paclitaxel Solubility in Aqueous Dispersions and Mixed Micellar Solutions of Lecithin

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