Paklitaksel Nanopartiküllerinin Kalite Tasarımı Ile Geliştirilmesi ve Değerlendirilmesi

Abstract

Quality by design is an FDA initiative that is a science and knowledge-based approach to pharmaceutical development. The aim of this study was to develop and characterize paclitaxel nanoparticles prepared by o/w emulsification-solvent evaporation method and to identify and control critical source of variability in the process, and understand the impact of formulation components and process parameters on the critical quality attributes using a quality by design approach. For this, a risk assessment study was performed with various formulation and process parameters regarding their impacts on critical quality attributes of paclitaxel nanoparticles which were determined as particle size, zeta potential and encapsulation efficiency. The potential risk factors were identified using an Ishikawa diagram and screened by Plackett-Burman design and finally paclitaxel nanoparticles were optimized using Box-Behnken design. The optimized nanoparticle formulation was further characterized by FTIR, XRD, DSC, SEM, AFM and gas chromatography. These studies showed that there was no incompatibility between paclitaxel and PLGA, paclitaxel completely encapsulated into the nanoparticles and transformed from crystalline state to amorphous state while encapsulating. In addition, no dichloromethane residue was detected in paclitaxel nanoparticles. In vitro cytotoxicity test showed that the developed paclitaxel nanoparticles were more efficient than free paclitaxel in terms of antitumor activity. In conclusion, this study demonstrated that understanding the formulation and the process parameters with the philosophy of quality by design is useful for the optimization of complex drug delivery systems.