A One-Step Twin-Screw Melt Granulation with Gelucire 48/16 and Surface Adsorbent to Improve the Solubility of Poorly Soluble Drugs: Effect of Formulation Variables on Dissolution and Stability

Fenofibrate is an effective lipid-lowering drug; however, its poor solubility and high log p (5.2) result in insufficient absorption from the gastrointestinal tract, leading to poor bioavailability. In this study, a one-step continuous twin-screw melt granulation process was investigated to improve the solubility and dissolution of fenofibrate using Gelucire (R) 48/16 and Neusilin (R) US2 as the solubilizer and surface adsorbent, respectively. The formulations (granules) were prepared at different ratios of fenofibrate, Gelucire (R) 48/16, and Neusilin (R) US2 based on phase-solubility studies and characterized using dissolution, differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy analyses and studies on flow properties. In the phase-solubility studies, a linear relation was observed between Gelucire (R) 48/16 concentration and the amount of fenofibrate dissolved. In contrast, the dissolution rate of the prepared formulations was independent of the fenofibrate: Gelucire (R) 48/16 ratio and dependent on the Neusilin (R) US2 levels in the formulation. Increasing Neusilin (R) US2 levels decreased the rate of dissolution of the granules but improved the stability of the tablets under storage at accelerated stability conditions. Interestingly, higher Gelucire (R) 48/16 levels in the granules resulted in tablets with a hard matrix, which slowed disintegration and dissolution. All formulations exhibited improved dissolution compared to pure fenofibrate.