Optimization of Dialysis Process for Liposomal Formulation Using Design of Experiment

Abstract

Major goal of this work is to remove the solvent impurity from the formulation and external buffer exchange by the dialysis process. Dialysis process was done by additional buffer solution to maintain the osmolarity of the formulation. The Purpose of the study was to evaluate the different diafiltration process parameter for the efficient product encapsulation and removing solvent from the stable nanoparticle dispersion. Impact of various process operations on subsequent Nano particulate separation and hence, maximum product recovery was analyzed. Two statistical designs were used in this study as part of an investigation into the possibility and the advantages of applying QbD concepts to diafiltration process. First design (Plackett–Burman) was used to screen high-risk variables obtained from risk analysis and assess their impact on diafiltration process and after that applying the central composite design (CCD) (with more predictive capability) to fully explain the relationship between the variables. Results showed that the trans-membrane pressure and the concentration factor of the feed was major variable for the desire filtration process. Lipidic Nano particle (LPN) separation was done by the tangential flow filtration method. A tangential flow filtration (TFF) system was estimated to purify PEGylated lipid nanoparticles. After sufficient removal of the impurities from the formulation, drug loading was done to better encapsulation of the drug in to the nanoparticle. Minimum concentration of the external buffer concentration for better encapsulation efficiency was also determined at the different level of the diafiltration process. A micro scale cross flow filtration device was designed to concentrate the desired product in the retentate. Overall, the results illustrate the power of micro scale techniques to identify and enable the understanding of key process performance attributes in a Diafiltration process sequence.