vesicular systems, like transferosomes, niosomes, ethosomes, and bilosomes have

been magnificently developed using QbD principles, with systematic optimization of

various CQAs like vesicle size, poly-dispersity index (PDI), loading capacity, the

skin retention and percent diffusion (Shukla et al. 2011; Garg et al. 2016a, b).

18.5.1.2 Non-Vesicular Systems

Lipidic nanocarriers are generally colloidal carriers with their particle size as

1000 nm or less (Yasir and Sara 2013; Singh et al. 2018a, b). Invariably, based

upon the composition of solid lipids and different functional excipients, such

systems can be classified as solid lipid nanoparticles (SLNs), nanostructured lipidic

carriers (NLCs), drug-lipid conjugates and lipospheres (Patil et al. 2015; Garg et al.

2016a, b; Sharma et al. 2017; Karunanidhi et al. 2018).

A polymer or a mixture of polymers is used as stabilizer and a matrix is used to

entrap lipophilic and hydrophilic drugs. NLCs are the second generation of lipid-

based nanoparticles, developed by moderate addition of liquid lipid (oil) and solid

lipid. The major benefits of NLCs include higher drug encapsulation efficiency,

better regulation of drug release kinetics and improved drug retention within the

system, upon storage (De Crozals et al. 2016; Karunanidhi et al. 2018). The most

important CMAs that are taken into account during optimization of such drug

delivery systems include percentage of solid and liquid lipids and of surfactant,

while vital CQAs include % drug loading, particle size, PDI and % entrapment

efficiency (Garg et al. 2017a).

18.5.1.3 Emulsifying Systems

These are fundamentally the biphasic systems of lipidic and aqueous phases, often

along with an apt emulsifier to emulsify both of these phases. Self-emulsifying

delivery systems turned out to be one of the most promising drug delivery systems

for peroral administration of biopharmaceutically challenged drug molecules. These

are isotropic anhydrous mixtures of drug with lipid, surfactant and/or co-surfactant.

Upon administration and getting in contact with gastric fluid in the gastrointestinal

tract, these systems get emulsified and tend to form micro-/nano-globules (Singh

et al. 2009a, b; Korting and Monika 2010). Based upon the nanometric size of the

globules, thus formed, after their dilution, these systems can be christened as self-

nanoemulsifying drug delivery systems (SNEDDS). Micelles constitute another kind

of emulsifying system, which tend to get formed by self-assemblage of the amphi-

philic excipient(s) in the aqueous phase with their hydrophilic portion facing the

outer micellar surface and the lipophilic portion remaining within the core (Singh

et al. 2014; Bhatia 2017). A quicker emulsification process tends to form nano-sized

micelles with higher surface area, thus resulting in accelerated drug release. During

their optimization, the amounts of lipid, surfactant and co-surfactant are employed as

CMAs, while the % drug release, globule size, emulsification time and zeta potential

are usually assessed as the CQAs.

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QbD-Steered Systematic Development of Drug Delivery Nanoconstructs:. . .

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