Enhancement of docetaxel solubility using binary and ternary solid dispersion systems

Abstract

Context: Poor biopharmaceutical properties and toxicities associated with the intravenous formulation of docetaxel (DTX) necessitate the exploration of an alternate oral route of delivery.

Objective: This study aims at enhancing the solubility of poorly soluble drug, DTX with the help of solid dispersion (SD) technique.

Method: 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).

Results and Discussion: 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.

Conclusion: Among all the excipients tested, Soluplus dispersion is the most promising candidate for oral formulation development.

• Anti-cancer
• apparent solubility
• freeze-drying
• solubility parameter
• Soluplus

Acknowledgements

The authors would like to acknowledge the technical support provided by Dr. Daniel Tune (Flinders Centre for NanoScale Science and Technology, Flinders University, Adelaide) in taking SEM images, Md. Morshed Alam (BASF Australia Ltd) for generously providing Soluplus® and Kolidon® 12PF and Ian Harvey Arellano (University of South Australia, Adelaide) for providing suggestions in manuscript writing.

Declaration of interest

The authors report no declarations of interest.

Supplementary material available online

Supplementary materials (S1-S2)