Solubility and Dissolution Enhancement of Ivacaftor Tablets by Using Solid Dispersion Technique of Hot-Melt Extrusion - A Design of Experimental Approach

Abstract

Objective: The objective was to improve the solubility and dissolution of ivacaftor tablets by using solid dispersion (SD) technique.Methods: Ivacaftor is practically insoluble (<0.001 mg/mL) over pH value of 3.0–7.5 due to low solubility, and it shows poor bioavailability after oral administration. Therefore, SDs of Ivacaftor were prepared by SD technique of hot-melt extrusion (HME) by adding different polymers such as Soluplus, Hypromellose 5 cps, and Copovidone with surfactants sodium lauryl sulfate, poloxamer, and polysorbate 80 to enhance its solubility.Results: After the analysis of Fourier-transform infrared spectrometry, X-ray diffraction, and differential scanning calorimetry of SDs by HME shows a converted in crystalline structure form to an amorphous structure form of Ivacaftor. The results show that the formulation of Ivacaftor SDs by HMT has enhanced the solubility and dissolution of Ivacaftor.Conclusion: In the present study, the SDs of the poorly soluble drug substance Ivacaftor were successfully prepared using HME. The in vitro dissolution test shows a significant increase in dissolution rate of SDs prepared by HME (95%) in formulation FHM8 compared with plain Ivacaftor (9%) within 30 min.

Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability

“…The extensive literature survey on LDV and SBV indicated that there was only one research work was published regarding the development of fast disintegrating tablets of LDV only [12]. This indicates that there is a large scope for performing research on this newly approved fixed dose combination drugs towards improving their bioavailability.…”