**1. Introduction**

Due to the continuous rise in the number of low solubility drug molecules and lack of more targeted drug therapies, the drug development has become more complex and challenging job within the industry. In fact, up to 90% of today's drug candidates are suffering from low aqueous solubility, which is commonly associated with low bioavailability, high intra‐ and inter‐subject variability and lack of dose suitability [1, 2]. In keeping these challenges in mind, drug formulators must seek new techniques and innovative formulation approaches to overcome such hurdles and ensure effective treatments for the patients in need.

It is more than a decade, when lipid‐based formulations have been considered as a well‐ established strategy for improving oral bioavailability and minimizing variable food effect of poorly soluble compounds. Lipids have been used as carriers in various delivery systems for drug administration, including solutions, suspensions, emulsions, and more attractively self‐ emulsifying/microemulsifying/nanoemulsifying drug delivery systems (SEDDS/SMEDDS/ SNEDDS) that are designed to increase solubility and bioavailability of drugs belonging to the BCS Class II–IV [3]. Among several approaches, which are currently available to incorporate active pharmaceutical drugs into lipid vehicles in a variety of dosage forms, SEDDS, SMEDDS and or SNEDDS have proved to be the most successful approaches in improving the bioavail‐ ability [4]. The initial key achievement of these formulation systems (SEDDS/SMEDDS/ SNEDDS) is to increase the solubilization of the poorly water soluble drugs (PWSDs) by the formation of emulsions and or micellar systems (colloidal solutions).

These systems advantageously present the drug in solubilized form, and their relatively smaller droplet sizes provide a large interfacial area enhancing the activity of pancreatic lipase to hydrolyze triglycerides and thereby promoting faster drug release containing mixed micelles of bile salts. The development of Neoral® (cyclosporin A) as a commercial product exhibits an excellent example of the utilization of these systems [5].

Nanotechnology has become a buzzword for scientific experts, and efforts are ongoing to extend its applications in various medical and pharmaceutical aspects. The nanoscale tech‐ nologies can be generally categorized into: lipid‐based nanocarriers, polymeric nanocarriers, inorganic nanocarriers, and drug nanoparticles or nanosuspensions [6]. Within the lipid‐based nanocarriers category, there has been a resurgence of interest in nanoemulsions since low energy emulsification methods, such as spontaneous or self‐nanoemulsification, have been developed. SNEDDS are anhydrous homogenous liquid mixtures, composing oil, surfactant, drug and/or cosolvents, which spontaneously form transparent nanoemulsion (20–250 nm droplet size) upon aqueous dilution with mild agitation [6, 7].

Being nanosized, SNEDDS offer a strong alternative to the more conventional oral formula‐ tions of lipophilic compounds. SNEDDS introduce the drug in solution within nanosized oil droplets. These fine droplets are emptied rapidly from the stomach resulting in faster drug release all over the gastrointestinal (GI) tract. An additional advantage of SNEDDS over simple oily solutions is granting much larger interfacial area for partitioning of the drug between oil and water leading to ease of dispersibility [8]. In contrast to oily solutions, SNEDDS does not depend on the action of bile salts, enzymes and/or other effects related to the (fed/fasted) state of the stomach [9]. Thus, SNEDDS can reduce the variability in rate and extent of absorption and grant more reproducible plasma concentration levels [10].

Compared with conventional nanoemulsions, SNEDDS can offer the advantages of improved physical and/or chemical stability of the formulation and ability to fill them into unit dosage forms, such as soft/hard capsules, which improve their commercial viability, patient compli‐ ance/tolerability and reduce palatability‐related concerns [6]. A key feature of a successful SNEDDS formulation is its capability to hold the drug in solution, throughout the GIT, for sufficient time to allow for absorption [11]. Many PWSDs have high solubility in SNEDDS formulations but could make a risk of precipitation after aqueous dispersion of the formulation or during its digestion in the intestine [12].

The current chapter will provide all the information to probe factors which influence the selection of successful lipid nanoformulations and affect the fate of the PWSDs after oral administration. The investigational research presented in this chapter will also provide additional information regarding current practice of lipid formulations with a particular emphasis on self‐nanoemulsifying drug delivery systems (SNEDDS), the trends and perspec‐ tives and the fate of PWSDs formulated in SNEDDS.
