Enhancement of docetaxel solubility using binary and ternary solid dispersion systems

<p><i>Context</i>: Poor biopharmaceutical properties and toxicities associated with the intravenous formulation of docetaxel (DTX) necessitate the exploration of an alternate oral route of delivery.</p> <p><i>Objective</i>: This study aims at enhancing the solubility of poorly soluble drug, DTX with the help of solid dispersion (SD) technique.</p> <p><i>Method</i>: DTX SDs were formulated with selected solubilizers, including Kollidon 12PF, Lutrol F68, Soluplus and Hydroxypropyl-β-cyclodextrin in different weight ratios. Freeze-drying method was used to prepare the binary and ternary SDs. Kinetic solubility of the SDs was evaluated in order to select best DTX-solubilizer combination. Best performing combination was then characterized using differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).</p> <p><i>Results and Discussion</i>: Among all SDs tested, Soluplus outperformed all the excipients at equivalent weight ratio. Binary SD of DTX and Soluplus (1:10) resulted in the highest improvement in solubility (362.93 ± 11.01 µg/mL). This is approximately a 93-fold increment as compared to the solubility of crystalline DTX (3.9 ± 0.2 µg/mL). This exceptional performance can be attributed to solid-state transformation as well as micellization.</p> <p><i>Conclusion</i>: Among all the excipients tested, Soluplus dispersion is the most promising candidate for oral formulation development.