Paclitaxel solubility in aqueous dispersions and mixed micellar solutions of lecithin.
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 100 mg/100 ml or higher for at least 24 h. 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 570 mg/100 ml) was achieved in 5% WLD. Dissolved PTX precipitated from all tested formulations over 24 h. Despite this, concentrations of dissolved PTX of 100 mg/100 ml or higher were observed after 24 h in 5% egg WLD, 1-5% soya WLD, and in 5% MM (lecithin : deoxycholate ratio 1 : 1 w/w). When four different batches of 5% egg WLD were prepared, containing PTX in clinically relevant concentration of 100 mg/100 ml, no precipitation of PTX was observed within 24 h 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.
Sznitowska
Malgorzata
M
Department of Pharmaceutical Technology, Medical University of Gdansk, Poland. msznito@amg.gda.pl
Klunder
Malgorzata
M
Placzek
Marcin
M
D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004655:Emulsions; D005612:Freeze Drying; D054709:Lecithins / Q000737:chemistry* / Q000493:pharmacokinetics; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D014867:Water / Q000737:chemistry
D004337:Drug Carriers; D004655:Emulsions; D054709:Lecithins; D014867:Water; D017239:Paclitaxel