**1. Introduction**

In recent years, solid dispersion technology by milling technique was largely utilized by researchers in order to enhance dissolution rate, bioavailability and thus therapeutic efficiency of several poorly water-soluble drugs (**Table 1**), as it represents a simple, economic and environmental process without using solvents [1–9]. In fact, millings enable particle size reduction and promote the formation of drug nanoparticles, which enhance solubility, flow properties and content uniformities of pharmaceutical dosage forms [10]. However, this process might induced


**Table 1.**

*Some examples of drug molecules exhibiting solubility enhancement by binary solid dispersion using co-milling technique [1–9].*

drug transition from crystalline to amorphous state which is more soluble in water but physically unstable in some cases [11]. Physical stabilization of such unstable amorphous material required an optimization strategy using additives (milling time and rate, compatible carriers with optimized proportion) in order to preserve its chemical integrity (absence of degradation) and inhibiting phase transformations or polymorphic conversion towards unstable forms [11]. In some cases, the stabilization and solubilization efficiency of binary solid dispersion is weak by exhibiting limited bioavailability enhancement [12] and required a large amount of carriers. In order to further enhance drug dissolution rate, several researchers have introduced third compound in drug formulations, this led to simultaneous enhancement of drug solubility and physical stability [13–19]. In this chapter, the challenges and strategies in developing robust ternary solid dispersion of high stability and performance are briefly discussed.
