Abstract
A well characterized Nanosomal Docetaxel Lipid Suspension (NDLS) formulation was developed without using any detergent or toxic organic solvents to avoid hypersensitivity reactions caused by the marketed Taxotere® product. The lyophilized NDLS formulation was easily resuspended in water and found to be physically and chemically stable for 48 hours. Physico-chemical characterization of NDLS confirmed a homogeneous formulation with an average particle size of less than 100 nm. Percent Docetaxel association with lipids in NDLS formulation was found to be greater than 95%. The in-vitro release assay showed a sustained release of 25% Docetaxel after 4 hours and 100% Docetaxel release after 42 hours of incubation. Sub-chronic toxicity in mice and rats showed comparable safety to Taxotere®. However, a pharmacokinetics study in rats revealed greater systemic availability of Docetaxel after administration of NDLS compared to Taxotere®. Further, a comparative safety and pharmacokinetic crossover study at 75 mg/m2 of NDLS and Taxotere® in patients with advanced solid tumor also showed higher exposure of Docetaxel with NDLS formulation than patients treated with Taxotere® formulation.
Highlights
Taxanes are cytotoxic diterpenes used clinically to treat cancer patients
To avoid toxicities associated with the excipients such as polysorbate 80/ethanol, and to improve quality of patient’s life, a well-characterized Nanosomal Docetaxel Lipid Suspension (NDLS) formulation was developed using Generally Recognized as Safe (GRAS) lipid excipients
The lipid based drug delivery system has been successfully used for various pharmaceuticals products to provide less toxic drug formulations that result in better quality of life for patients [11,12,13]
Summary
Taxanes are cytotoxic diterpenes used clinically to treat cancer patients. Among the taxanes, the use of Docetaxel is higher due to its enhanced efficacy in most types of cancers especially breast cancer [1] and non-small-cell lung cancer [2]. The lipid based drug delivery system has been successfully used for various pharmaceuticals products to provide less toxic drug formulations that result in better quality of life for patients [11,12,13]. This may be due to the altered pharmacological distribution and minimal interaction with red blood cells (RBCs) [14]. One of the limitations of all lipid or liposome based delivery systems is the use of organic solvents to solubilize water insoluble drug and lipids. A randomized crossover study is described to assess safety and pharmacokinetics of NDLS and Taxotere® in advanced solid tumor patients
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