Studies of the precipitation pattern of paclitaxel in intravenous infusions and rat plasma using laser nephelometry

Abstract

Cremophor EL (CrEL) is commonly used to solubilize paclitaxel (Ptx); a widely established anticancer agent used against many types of cancer. Using laser-based microplate nephelometry, in this work we assessed the precipitation kinetics of Ptx in CrEL-containing formulations upon dilutions with different infusion media or upon introduction into rat plasma. The precipitation profile of Ptx was assessed for a Taxol-like formulation and compared with a preparation with reduced CrEL content. These two formulations were diluted at various ratios in compatible infusion media and with or without rat plasma. The percentages of Ptx precipitated in dilution media and protein-binding in plasma were quantified using HPLC. The findings of turbidity measurements were in good agreement with HPLC. Despite the presence of albumin, it was possible to assess turbidity within infusion solutions and predict Ptx precipitation. Upon addition to plasma, no precipitation in Taxol-like formulation occurred after 2 h. In contrast, precipitation occurred immediately in CrEL-reduced formulation. It is possible that the high percentage of protein-bound Ptx in plasma (98.5-99.2%) has inhibited drug precipitation. Turbidity measurements using laser nephelometry can provide a rapid screening tool when developing intravenous formulations for poorly soluble drugs, such as Ptx and assess its stability upon dilution in animal plasma.

The correlation between paclitaxel chemotoxicity and the plasma albumin level in cancer patients

“…In addition, cancer patients often suffer from hypoproteinemia due to the disease itself and the adverse effects of long‐term radiotherapy and chemotherapy, such as poor nutritional status, loss of appetite, diarrhoea and kidney damage. Paclitaxel is a weakly acidic drug with a high plasma protein‐binding rate of 89%–98% 6,7 . The major components of human total serum proteins are albumin, globulin, and fibrinogen.…”

“…Paclitaxel is a weakly acidic drug with a high plasma protein-binding rate of 89%-98%. 6,7 The major components of human total serum proteins are albumin, globulin, and fibrinogen. As a weakly basic compound, albumin may be the major binding protein of paclitaxel in the blood, while globulin shows weak acidity.…”