**8. Effect of process parameters and formulation attributes on development of PBNDDS of plant extracts and its phytoconstituents**

Process parameters perspective injection rate, stirring speed, stirring time and processing temperature (solvent-antisolvent mixing) found to have marked impact on the average particle size, polydispersity and entrapment efficiency of PBNDDS [80–83, 93, 94]. It was observed that high injection rate and processing temperature found to have major impact leading to low average size of phospholipid based nano drug delivery systems (PBNDDS). Low stirring speed (<1000 rpm) and stirring time exhibit low average size of PBNDDS. Interactions between process parameter also have marked impact on average size of PBNDDS, where batches prepared using high injection rate and slow stirring speed demonstrate low average size (**Figure 7a** and **b**).

#### **Figure 7.**

*Two way interaction plots of [A] process parameters and [B] formulation attributes for average particle size of PBNDDS.*

Processing temperature found to be the most important process parameters which have significant impact on entrapment efficiency or loading of phytoconstituents on PBNDDS [83]. PBNDDS prepared using high temperature and injection rate leading to low entrapment efficiency. This phenomenon also probably related to low average size of PBNDDS developed at these conditions, while PBNDDS with high average particle size having high entrapment or loading efficiency. Polydispersity of PBNDDS was markedly affected by processing temperature and stirring speed and suggesting that batches processed at low temperature and high stirring speed found to be lessly polydispersed [81, 82].

Formulation attributes - ratio of drug: phospholipid and phospholipid: cholesterol, solvent system and its properties (phytoconstituents solubility, pH of the solvent), drug concentration found to have major impact on average particle size, polydispersity and entrapment efficiency of PBNDDS of phytoconstituents [80–83].

It is very imperative to find out the optimum level and amount of each of these process parameters and formulation attributes to achieve low average size with high entrapment or loading of phytoconstituents for PBNDDS. It was evident that not only the impact of individual parameters but its interactions also exhibited marked impact on the average size and loading of phytoconstituents for PBNDDS (**Figure 7**) [81–83].
