Paklitaksel Nanopartiküllerinin Kalite Tasarımı Ile Geliştirilmesi ve Değerlendirilmesi
Özet
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.
