Enhanced Solubility and Dissolution by Surface-Modified Solid Dispersion of Alectinib Hydrochloride

Abstract

Objective: Alectinib hydrochloride (AH), a poorly soluble drug, exhibits low solubility thereby very low bioavailability. The present study aims to develop and optimize surface-modified solid dispersion of AH (AH-SMSD) with enhanced solubility and dissolution using Soluplus® (SOL) and Gelucire 44/14 (GEL) as a polymer and surfactant, respectively. Methods: Design of Experiments (DoE) was implemented to optimize the weight ratio of SOL (X1), and GEL (X2), keeping the drug weight constant to maximize the solubility (Y1) and dissolution (Y2). The optimized solid dispersion was subjected to solubility and dissolution in bio-relevant media and characterized using differential scanning calorimetry (DSC), Powder X-ray diffraction (pXRD), Fourier-transform infrared (FTIR), and scanning electron microscopy (SEM). Results: A statistically significant model is obtained for solubility and dissolution through DoE. Formulation (F9) containing AH: SOL: GEL in weight ratios 1:5:5 showed a 547-fold increase in solubility. This solubility enhancement further translated into dissolution improvement with drug release of >80% in 15 min. The optimized formulation also showed improved solubility and dissolution in fasted-state bio-relevant media. DSC and pXRD showed a change in the crystallinity pattern of the drug. FTIR showed the existence of weak intermolecular interactions. Morphological evaluation through SEM demonstrated that the drug particles were dispersed to a hydrophilic carrier matrix, thus, transforming the hydrophobic drug into a hydrophilic form. Conclusion: AH-SMSD with enhanced solubility and dissolution was successfully developed. The optimized formulation also showed improvement in the bio-relevant media and therefore has the potential to improve in vivo oral bioavailability (however, needs to be experimentally explored).

Evaluation of Solubility, Dissolution Rate, and Oral Bioavailability of β-Cyclodextrin and Hydroxypropyl β-Cyclodextrin as Inclusion Complexes of the Tyrosine Kinase Inhibitor, Alectinib

“…For example, Eun Ji Park et al increased the solubility and dissolution of ALB using suspended self-nanoemulsifying drug delivery systems [ 29 ]. Sumit Kumar Saha et al utilized surface modification dispersion techniques to enhance the solubility and dissolution of ALB [ 30 ]. However, the current study is the first to investigate inclusion complexes of ALB with βCD and HPβCD with the aim of enhancing solubility, dissolution rate, and oral bioavailability.…”