Ternary Solid Dispersion Strategy for Solubility Enhancement of Poorly Soluble Drugs by Co-Milling Technique

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 co-milling 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 for six months)

Multifunctional Roles of PVP as a Versatile Biomaterial in Solid State

Polyvinylpyrrolidone (PVP) has proven to be a highly versatile material, as evidenced by its long history as multifunctional biomaterial with a wide range of high-performance applications (e.g., tissue engineering, drug delivery systems, and ophthalmologic applications). PVP was frequently used in medical and pharmaceutical field due to its several interesting properties (higher glass transition temperature, water solubility, biocompatibility, biodegradability, chemical stability, very good adhesive, and emulsifying agent). This chapter highlights the multifunctional roles of PVP in pharmaceutical formulations in solid state. In fact, PVP acted as a stabilizing agent for various amorphous drug molecules by minimizing their molecular mobility. Physical stabilization resulted from the reinforcement of intermolecular interactions in binary or ternary systems due to the synergetic effect of PVP. This made it possible to overcome several challenges for drug formulations (e.g., solubility and bioavailability weakness, physical instability under stress conditions, complexation efficiency of cyclodextrin molecules). In this chapter, the effect of PVP on the binary solid dispersion (indomethacin:kaolin) is discussed. We have shown that PVP enhanced physical stability of amorphous indomethacin under stress conditions (at RH: 75% and T = 40°C for three months), leading to the improvement of drug aqueous solubility by suppressing kaolin adsorption effect