concept and state of the art for the nanoemulsion and describes the applications of

nanoemulsions for herbal drug delivery.

19.2

Nanoemulsion: The State of the Art

Among the formulation considerations, nanoemulsions formulated with low-energy

methods relatively require high concentration of surface-active agents as compared

to the high-energy methods. A drawback of destabilization of micelles is associated

with higher concentration of surfactants utilized for the fabrication of nanoemulsions

by low-energy method. Such methods utilize only environmental changes and form

a spontaneous nanoemulsification system. On the other hand, high-energy methods

utilize

intensive

mechanical

forces

such

as high-pressure

homogenization/

microfluidization and ultrasonic waves. These intensive disruptive forces break

down the large droplets of dispersed phase into smaller droplets. Therefore, the

high-energy methods require relatively less concentration of surfactants as intensive

mechanical forces facilitate the size reduction of micelles (Salvia-Trujillo et al.

2016). Also, microemulsions due to its thermodynamic stability generally require

low-energy methods for preparation (Nastiti et al. 2017). The surface-active agents

can be ionic (anionic or cationic or zwitterionic) or nonionic (neutral) in nature and

depending on the nature these agents impart stability to nanoemulsions. For instance,

ionic emulsifiers induce electrostatic repulsion and prevent dispersed phase aggre-

gation. On the other hand, nonionic emulsifiers predominantly induce steric hin-

drance and reduce droplet aggregation (Aswathanarayan and Vittal 2019).

Nanoemulsions are nonequilibrium type of system which cannot be formed sponta-

neously, and external energy input is required to process the formulation. This

external energy facilitates to circumvent the challenge of interfacial tension between

the immiscible liquids and form kinetically stable nanoscale emulsified droplets for a

long time (Aboofazeli 2010). The importance of additional shear is to break the

micron size droplets into nano-range. The high shear required for formulating

nanoemulsions is due to the inverse relation of Laplace pressure with the curvature

radius (nonplanar surface), and mathematically it is denoted as ПL ¼ 2σ/r

(Bhattacharjee 2019; Mason et al. 2006). The ПL refers as Laplace pressure, σ as

interfacial tension between two immiscible liquids, and r as droplet radius. Laplace

pressure is defined as the pressure exerted by curved interface on the molecules

inside the droplet. This also signifies that smaller droplets have relatively high

Laplace pressure than larger droplets. Furthermore, nanoemulsions are thermody-

namically unstable and have positive value of Gibbs free energy on the formation of

nano-droplets. This is due to significant increase in surface area of while conversion

from large size droplets (micron/submicron) to small droplets. Consequently, the

magnitude for the change in the surface area of dispersed phase becomes positive,

and entropy of formed nanoemulsion is also more than zero or positive. Hence,

referring the following mathematical equation (Eq. 19.1), Gibbs free energy for

formed nanoemulsion becomes positive which signifies that the formation of

nanoemulsion is a non-spontaneous process (Barkat et al. 2020):

19

Nanoemulsions: A Potential Advanced Nanocarrier Platform for Herbal Drug. . .

353