Enhanced solubility and dissolution of Alectinib via amorphous solid dispersion with a novel polymer, Apinovex™

Alectinib (ALB) is a kinase inhibitor typically used for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer. The objective of the current study was to improve the solubility and dissolution of ALB, a poorly water-soluble drug, by formulating into an amorphous solid dispersion (ASD) using Apinovex^TM, a novel high molecular weight polyacrylic acid polymer. ASDs were prepared by the rotary evaporation technique with varying weight ratios of ALB and Apinovex^TM. Samples with up to 60 % ALB in ASDs displayed amorphous state of ALB in the formulation when analyzed via powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). Further, 40 % ALB ASD showed increased solubility and dissolution in FaSSGF, FaSSIF-V2, and FeSSIF-V2 media. Stability studies for 40 % ALB ASD formulation were conducted at room temperature (25 ± 2 ˚C/ 60 ± 5 % RH) and accelerated conditions (40 ± 2 ˚C/ 75 ± 5 % RH), and results showed stability up to 6 months, as demonstrated by drug content, DSC, PXRD, and dissolution. The observed increase in solubility and dissolution in bio-relevant media suggests potential for improved in vivo absorption, especially in the fed-state.These findings support the use of solid dispersion as a strategy to enhance the bioavailability of ALB.