Excipient effects on in vitro cytotoxicity of a novel paclitaxel self-emulsifying drug delivery system.
Paclitaxel is a potent chemotherapeutic agent currently administered intravenously in polyoxyethylated castor oil (Cremophor EL) and dehydrated ethanol (1:1) for the treatment of solid tumors. The objective of this work was to develop a novel self-emulsifying drug delivery system (SEDDS) devoid of cremophor for the i.v./oral delivery of paclitaxel and to investigate the in vitro cytotoxicity of the combined excipients. The SEDDS formulations were characterized in terms of droplet size using a ternary phase diagram. The Caco-2 cell line was used to monitor the cytotoxicity of the excipients. Cell viability was determined colorimetrically at 570 nm utilizing the MTT assay. The distribution of the formulations on the phase diagram indicated the presence of macroemulsions ( approximately 1 microm), submicron emulsions (50-200 nm), and microemulsions (below 10 nm). An increase in the sodium deoxycholate excipient content led to an increase in physical stability but caused more chemical degradation of the drug and more cytotoxicity. The drug in the novel SEDDS was chemically stable for at least 1 year when kept as a two-part formulation. The drug loading was increased by approximately fivefold compared to the marketed i.v. formulation; the excipients presented a significantly reduced cytotoxicity and led to a stable microemulsion.
Gursoy
Neslihan
N
Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, POB 12065 Jerusalem, 91120 Israel.
Garrigue
Jean-Sebastien
JS
Razafindratsita
Alain
A
Lambert
Gregory
G
Benita
Simon
S
D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
D045703:Emulsifying Agents; D005079:Excipients; D017239:Paclitaxel