5.1.1. Suspension Stability

The main role of stabilizers in NCM synthesis is to prevent the growth of crystals resulting in micro or macroparticles. However, most stabilizers may offer "stealth" properties, enhance permeation, prevent efflux, enhance cell-targeting, or prevent clearance. By careful formulation, the dissolution and stability can be enhanced while also improving permeation. Consequently performance may be altered by the selection of stabilizers as part of the critical formulation parameters (CFP) [156].

The majority of stabilizing agents are amphiphilic moieties that have the ability to adsorb to the surfaces of newly formed drug particles by utilizing hydrophilic-hydrophobic interactions. This results in an enhancement in the wetting of NC or NCC [155]. In its most classical form, the DLVO theory describes nanoparticle stabilization based on steric and/or electrostatic interactions. Steric stabilization, by use of polymers or non-ionic surfactants, has been more commonly utilized, and has an added facet of being temperature sensitive. Conversely, electrostatic stabilization is achieved with ionic polymers or surfactants. In systems where stabilization is achieved only by electrostatic forces, the ZP should be higher than |30| mV. As previously stated, this value is vulnerable to changes in pH, the presence of ionic species, and changes in hydration (drying) [155].

The physical stability of NCM is usually predicted in the suspension state by the value of the ZP [76]. The use of ZP as a predictor of stability has been shown to be applicable in nano-formulations containing nevirapine [157], efavirenz [158], and curcumin [105]. More specifically, NCM nanosuspensions of miconazole [159], indomethacin [160], and ascorbyl palmitate [161] exhibited ZP-dependent stability.
