Physicochemical Properties

**115**

**Chapter 6**

**Abstract**

for six months).

**1. Introduction**

aqueous solubility, bioavailability, Ibuprofen

Ternary Solid Dispersion Strategy

for Solubility Enhancement

of Poorly Soluble Drugs by

*Marouene Bejaoui, Hanen Oueslati and Haykel Galai*

Amorphous ternary solid dispersion has become one of the strategies commonly used for improving the solubility and bioavailability of poorly water soluble drugs. Such multicomponent solid dispersion can be obtained by different techniques, this chapter provides an overview of ternary solid dispersion by comilling method from the perspectives of physico-chemical characteristics in vitro and in vivo performance. A considerable improvement of solubility was obtained for many active pharmaceutical ingredients (e.g., Ibuprofen, Probucol, Gliclazid, Fenofibrate, Ibrutinib and Naproxen) and this was correlated to the synergy of multiple factors (hydrophilicity enhancement, particle size reduction, drug-carrier interactions, anti-plasticizing effect and complexation efficiency). This enhanced pharmacokinetic properties and bioavailability of these drug molecules (1.49 to 15-folds increase in plasma drug concentration). A particular focus was accorded to compare the ternary and binary system including Ibuprofen and highlighting the contribution of thermal and spectral characterization techniques. The addition of polyvinylpyrrolidone (PVP K30), a low molecular weight molecule, into the binary solid dispersion (Ibuprofen/β-cyclodextrin), leads to a 1.5–2 folds increase in the drug intrinsic dissolution rate only after 10 min. This resulted from physical stabilization of amorphous Ibuprofen by reducing its molecular mobility and inhibiting its recristallization even under stress conditions (75% RH and T = 40°C

**Keywords:** amorphous ternary solid dispersion, co-milling, PVP, physical stability,

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

Co-Milling Technique
