19.5.2.3 Solvent Diffusion Method

In solvent diffusion method, oily components are mixed into organic solvents like

ethanol, acetone, ethyl acetate, isopropyl acetate, etc. The prepared oily phase is then

mixed in aqueous phase consisting of surfactant or surfactant mixture with continu-

ous stirring. The agitation caused by the stirring in the system forms nano-droplets.

The organic solvent is then removed from the system using rotary vacuum evapora-

tor. The safety consideration of organic solvent is important in this method as the

solvent has to be safe in terms of toxicity. Also, the solvent should have miscibility

with both the oil and aqueous phases. The concentration of organic solvent along

with the concentration of oil, surfactant, and water plays an influential role in the

determining the formation of nanoemulsion and its stability (Porras et al. 2008;

Bouchemal et al. 2004).

19.6

Application of Nanoemulsion for Herbal Bioactives

Herbal bioactives have been pharmacologically utilized for the treatment of various

diseases. Despite the huge potential of phytopharmaceuticals (herbal extracts and

bioactives), their pharmaceutical application is limited due to poor water solubility,

membrane permeability, and limited bioavailability. All these issues can be resolved

through nanoemulsion technology wherein the active compound is encapsulated in

nano-droplets dispersed in continuous medium. Also, self-nanoemulsifying system

has the property to transform into nano-droplets when comes in contact with gastric

environment and additional energy required for the formation of nanoemulsion is

provided by the gastrointestinal motility itself. Such type of nanoemulsions is also

known as self-emulsifying nanoemulsion. The dispersed phase rapidly diffuses into

the continuous phase and instantaneously forms nanoscale emulsions in vivo. Such

nanoscale emulsions usually carry low oil content and high concentration of surfac-

tant or surfactant mixture which enables to form o/w nanoemulsion spontaneously

(Kumar et al. 2019). Nanoemulsion also provides stability to phytopharmaceuticals

from gastric degradation and can also impart controlled release pharmacokinetics.

Several herbal phytopharmaceuticals (quercetin, camptothecin, rutin, genistein, res-

veratrol) have been reported to be delivered using nanoemulsion technology primar-

ily with an aim to improve their permeability through the gastrointestinal membrane

and skin (Salvia-Trujillo et al. 2016; McClements and Xiao 2017; Aboalnaja et al.

2016; Rahman et al. 2020).

The important challenge associated with phytopharmaceuticals is their variable

bioavailability that may produce nonuniform therapeutic effects. This is the reason

phytopharmaceuticals are unable to produce favorable therapeutic action consis-

tently and sometimes cannot satisfy the medical community. This nonuniformity

causes uncertainty in treating disease and reduced level of significance in statistical

clinical data. There are mainly three major factors that influence the oral bioavail-

ability of phytopharmaceuticals, i.e., (1) the dose of the herbal extract or bioactive to

be ingested and fraction available for dissolution in gastric environment (this factor

can be a rate-limiting factor for most of the herbal bioactives because of their

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