Development and Evaluation of Paclitaxel Nanoparticles Using a Quality-by-Design Approach

The aims of this study were to develop and characterize paclitaxel nanoparticles, to identify and control critical sources of variability in the process, and to understand the impact of formulation and process parameters on the critical quality attributes (CQAs) using a quality-by-design (QbD) appro...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmaceutical sciences 2013-10, Vol.102 (10), p.3748-3761
Main Authors: Yerlikaya, Firat, Ozgen, Aysegul, Vural, Imran, Guven, Olgun, Karaagaoglu, Ergun, Khan, Mansoor A., Capan, Yilmaz
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Box–Behnken
Chemistry, Pharmaceutical - methods
design of experiments
Drug Delivery Systems - methods
formulation
mathematical model
multivariate analysis
nanoparticles
Nanoparticles - chemistry
paclitaxel
Paclitaxel - chemistry
Particle Size
Plackett–Burman
polymeric drug delivery systems
quality by design
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The aims of this study were to develop and characterize paclitaxel nanoparticles, to identify and control critical sources of variability in the process, and to understand the impact of formulation and process parameters on the critical quality attributes (CQAs) using a quality-by-design (QbD) approach. For this, a risk assessment study was performed with various formulation and process parameters to determine their impact on CQAs of nanoparticles, which were determined to be average particle size, zeta potential, and encapsulation efficiency. Potential risk factors were identified using an Ishikawa diagram and screened by Plackett–Burman design and finally nanoparticles were optimized using Box–Behnken design. The optimized formulation was further characterized by Fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy, atomic force microscopy, and gas chromatography. It was observed that paclitaxel transformed from crystalline state to amorphous state while totally encapsulating into the nanoparticles. The nanoparticles were spherical, smooth, and homogenous with no dichloromethane residue. In vitro cytotoxicity test showed that the developed nanoparticles are more efficient than free paclitaxel in terms of antitumor activity (more than 25%). In conclusion, this study demonstrated that understanding formulation and process parameters with the philosophy of QbD is useful for the optimization of complex drug delivery systems. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3748–3761, 2013
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.23686