Pharmaceutical aspects of paclitaxel

Paclitaxel is one of the most important lead compounds to emerge from a natural source. Because of the complex and unusual chemistry of paclitaxel, it is mainly extracted from the bark of a slow growing Western yew. Although total chemical synthesis of paclitaxel has been achieved, it may not be feasible commercially. Paclitaxel has a low therapeutic index: it is highly lipophilic and practically insoluble in water. The commercially available injection preparation is a sterile solution of the drug in Cremophor(R) EL and dehydrated alcohol. Present-day cancer chemotherapy with paclitaxel frequently causes hypersensitivity reactions. The major hurdles for successful therapy with paclitaxel are the availability of the drug and its delivery. The importance of developing an improved delivery system for paclitaxel is obvious from the problems seen from present-day therapy. Hence, the current approaches are mainly focused on: (1) developing formulations that are devoid of Cremophor(R) EL, (2) the possibility of large-scale preparation; and (3) stability for longer periods of time. The path to identify new molecules with better therapeutic efficacy will continue to be an integral part of health care systems, but the author is emphasizing the importance of 'better delivery of drugs' which is going to further refine the therapy. The different approaches investigated so far have shown much promise in replacing the Cremophor(R) based vehicle for paclitaxel delivery. However, the final product for human use is still far away. Therefore this review is the first comprehensive account of the pharmaceutical aspects of paclitaxel, with special emphasis on its delivery. (C) 1998 Elsevier Science B.V. All rights reserved.