| Autor: |
Majeed BJM; Faculty of Pharmacy, Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan., Saadallah MA; Faculty of Pharmacy, Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan., Al-Ani IH; Faculty of Pharmacy, Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan., El-Tanani MK; Faculty of Pharmacy, Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan.; College of Pharmacy, RAK Medical and Health Sciences University, Ras Al-Khaimah P.O. Box 12973, United Arab Emirates., Al Azzam KM; Department of Chemistry, Faculty of Science, The University of Jordan, Amman 11942, Jordan., Abdallah HH; Chemistry Department, College of Education, Salahaddin University, Erbil 44002, Iraq., Al-Hajji F; Faculty of Pharmacy, Applied Science University, Amman 11937, Jordan. |
| Abstrakt: |
This study aims to improve the solubility and dissolution rate of alectinib (ALB), a tyrosine kinase inhibitor commonly used for treating non-small-cell carcinoma (NSCLC). Given ALB's low solubility and bioavailability, complexation with β-cyclodextrin (βCD) and hydroxy propyl β-cyclodextrin (HPβCD) was evaluated. Some of the different preparation methods used with varying ALB-to-CD ratios led to the formation of complexes that were characterized using Fourier-Transform Infrared (FTIR) techniques and Differential Scanning Calorimetry (DSC) to prove complex formation. The encapsulation efficiency was also determined. The simulations were carried out for ALB's interactions with βCD and HPβCD. This study identified the most soluble complex (ALB-HPβCD; 1:2 ratio) and evaluated its dissolution. The bioavailability of the ALB-HPβCD complex was evaluated in Wistar rats relative to free ALB. Pharmacokinetic profiles revealed increased Cmax (240 ± 26.95 ng/mL to 474 ± 50.07 ng/mL) and AUC0-48 (5946.75 ± 265 ng.h/mL to 10520 ± 310 ng.h/mL) with no change in the elimination rate constant. In conclusion, the complexation of ALB-HPβCD manages to increase in vitro solubility, the dissolution rate, and oral bioavailability, providing a favorable approach to improving ALB administration. |
