The purpose of this work was the development of a continuous process for manufacturing solid oral dosage forms containing itraconazole (ITZ), a model poorly soluble drug. In order to improve its bioavailability, its aqueous solubility must be enhanced.

One useful method for increasing the solubility of these drugs is the conversion of the crystalline form into its amorphous form to obtain an amorphous solid dispersion (ASD) by hot melt extrusion (HME). Soluplus® (SOL) was chosen as the main polymer matrix due to its ability to interact with ITZ and to stabilize its amorphous form. However, SOL exhibits a “gel effect” in solution which slowed down the release of ITZ. A screening study enabled the selection of gel-breaking excipients that were used in a design of experiment (DoE) to optimize the formulation. In parallel, the limits of the HME process parameters were also determined and included in the DoE. The optimum formulation was the one containing 2.5 wt. % of AcDiSol® produced at 155 °C and 100 rpm. Moreover, the design space around the optimum was determined.

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