Progress in the development of alternative pharmaceutical formulations of taxanes.
The currently available taxanes paclitaxel (Taxol) and docetaxel (Taxotere) are clinically effective against advanced breast, ovarian and non-small cell lung cancer. Due to their low aqueous solubility, both taxanes posed difficulties to the pharmaceutical scientists with respect to the development of an intravenous dosage form. At present, paclitaxel is formulated in a mixture of 50:50% (v/v) Cremophor EL and dehydrated ethanol. However, this formulation vehicle is associated with a number of pharmacological, pharmacokinetic and pharmaceutical concerns amongst which serious hypersensitivity reactions. This review deals with the attempts made into the development of alternative dosage forms of paclitaxel devoid of the Cremophor EL/ethanol excipients and potential future taxane formulations.
Nuijen
B
B
Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam. apbnu@slz.nl
Bouma
M
M
Schellens
J H
JH
Beijnen
J H
JH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003505:Cyclodextrins / Q000737:chemistry*; D000077143:Docetaxel; D004339:Drug Compounding / Q000379:methods; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D003505:Cyclodextrins; D004655:Emulsions; D011355:Prodrugs; D012997:Solvents; D013501:Surface-Active Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel