Abstract

LYOPHILIZATION OF CABAZITAXEL NANOPARTICLES FOR IMPROVING PHYSICAL STABILITY AND PRODUCT SHELF-LIFE

Mahesh Paithankar* and Mangesh Bhalekar

ABSTRACT

Cabazitaxel (CTX) is a novel taxane derivative effective in the treatment of docetaxel-resistant metastatic prostate cancer. Previously, we have developed surfactant-free Cabazitaxel nanoparticulate system (CTX NPs) to overcome the problems of poor water solubility of drug and mitigate the toxicity associated with use of surfactant in the existing formulation. Herein, the present work aims to enhance physical stability and shelf-life of prepared CTX NPs using lyophilization approach. Thermal and crystallization behaviour of CTX NPs were studied using Differential scanning calorimetry (DSC) analysis and Freeze drying microscopy. DSC analysis indicated that crystallization of product solution occurs at –18.19°C. The collapse temperature (Tc) determined using freeze drying microscopy devoid of annealing step was -24.5 ⁰C, while Tc with annealing step was -23.7°C demonstrating no significant impact of annealing. Based on knowledge of Tc, the shelf temperature during primary drying was appropriately set so that the product temperature remained below -24.5 ⁰C. Notably, lyophilized of CTX NPs showed desired critical quality attributes such as particle size, % drug association, assay and impurity levels. Prepared formulation showed excellent stability when stored at real-time (2-8 ⁰C) and accelerated stability conditions (25 ⁰C/60% RH). Thus, present study demonstrate role of lyophilization in improving physical and shelf-life stability of nanoformulation.

Keywords: Cabazitaxel, Nanoparticulate system, Lyophilization, Stability, Collapse temperature.