Nanopharmaceutical Advanced Delivery Systems

Table 1.2 Differences between SMEDDS, SEDDS, and SNEDDS.

Cubosomes and hexosomes have generated great attention as they are the first to have molecular, multilevel, mesophasic, and nanoparticle observed structural compounds. They can be administrated through various routes thus providing versatility in the administration of various drugs. Internal structure defined before dispersion by liquid crystal mesophases of amphiphiles offers complex topologies; they can carry a higher volume of drug with long-term release [75]. Size ranges vary in the nanometer range, which allows similar surfactant to uniformly distribute and prevent aggregation. Since it possesses the curvature in the internal structure of crystalline mesophases, large volume of the drug can be loaded, which increases the potential for drug targeting [76, 77]. Due to the amphiphilic nature of liquid crystal forming lipid (polar head and lipophilic tail), they arrange themselves into a cubic or hexagonal phase, which is thermodynamically stable. Therapeutic applications of liquid crystal nanoparticles (cubosomes and hexagonal) are associated with the drug, route of delivery, formulation, and physiochemical properties such as increased molecular weight, the different polarity of drug molecule, compatibility issue, enzymatic degradation, and reduced toxicity.

There are various high energy input and low energy input methods available for the preparation of lipid-based nanocarriers. The methods presented here include physical ones like homogenization and chemical ones like co-acervation. The choice of methods and energy input depends on the thermal stability of lipid molecules as well as drug molecule. Several important methods utilized for the preparation of lipid nanocarriers are given in Table 1.3.

The development of the lipid-based nanocarrier system can easily be scaled using the reported approach for preparation. Several issues of stability can, however, be associated with lipid carriers and can be a hurdle in the process of the scale-up. Polymorphism must first be taken into account. The colloidal size and particularly their high volume-to-surface ratio can result in the decrease in melting points. This effect may also be caused by impurities, agents, and stabilizers [86, 87]. For example, the co-acervation and hot homogenization method of fatty acids and triglycerides results in polymorphism [88]. Due to rapid solvent evaporation, polymorphic forms have been obtained during spray drying.

Table 1.3 Different types of techniques used in the preparation of lipid nanocarriers.

Furthermore, sterilization is an important stability parameter in lipid nanocarrier system production [89]. Irradiation is an existing technique of sterilization for pharmaceuticals. However, during irradiation, the chemical degradation of the lipids can occur: therefore, ionizing radiation is not allowed, or at least more tests are required before it is accepted as a safe and effective technique of sterilization. Diverse studies have preferred an autoclave approach because it doesn’t change the Zeta potential and mean particle size, although this is paradoxical considering the effect that temperature may influence the stability of nanoparticles.

Another significant cause for instability is phase separation [88] because of the formation of reversible or irreversible particles (coalescence, sedimentation); also during storage, gelling may occur. Adequate surfactants can be used to address these problems: they can stabilize LNP suspension by an electrostatic repulsion, which improves Zeta potential, or they can serve as steric (non-ionic surfactants) stabilizers. Surface stability, particularly electrostatic stabilization and Zeta potential, is highly sensitive to pH and eventually exists at the external phase, which may cause suspension destabilization.

The acquisition of solid water forms is an effective strategy for overcoming the problems concerning lipid nanocarrier storage stability. This can be achieved through spray drying or lyophilization of suspension.