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.

Esomeprazole is used in various clinical settings where a decrease in gastric acid production is desired since it is a proton pump inhibitor. Apixaban, an anticoagulant, is used to reduce the risk of stroke in patients with certain cardiovascular diseases. This research aims to examine the effects of giving esomeprazole and apixaban to rats simultaneously, as well as to measure their pharmacokinetics and look for statistical differences or interactions. A method for the simultaneous determination of esomeprazole and apixaban in rat plasma was developed using HPLC/MS and validated by ICH guidelines. Five groups of Wistar rats were created, and the drugs were administered as follows: esomeprazole (5 mg/kg) intravenously, apixaban (125 mcg/Kg) intravenously, esomeprazole (5 mg/kg) orally, apixaban (250 mcg/kg) orally, and esomeprazole (5 mg/kg) and apixaban (250 mcg/kg) both orally. Both drugs' concentrations were measured in plasma samples collected on a predetermined schedule. The pharmacokinetics of both drugs were calculated and statistically analyzed using a 90% confidence interval and non-compartmental analysis. When the two drugs were combined, apixaban’s C_max and AUC increased while esomeprazole’s C_max and AUC decreased. On the other hand, Apixaban’s T_max decreased with an increase in esomeprazole’s T_max, indicating a possible interaction between the two drugs. When both drugs were taken together, their bioavailability was reduced, implying that less esomeprazole was absorbed over time.

Background and Purpose: Apixaban (AP) is a factor X inhibitor, an orally active drug that inhibits blood coagulation for better prevention of venous thromboembolism. It has poor solubility, dissolution rate and low bioavailability. The aim of this study was to improve the aqueous solubility and dissolution rate of oral AP as a step to enhance its bioavailability by preparing it as an inclusion complex with beta- and hydroxy propyl beta-cyclodextrin. Experimental Approach: A simple, rapid method of analysis of AP was developed using ultraviolet spectrophotometry (UV) and partially validated in terms of linearity, precision and accuracy, recovery, and robustness. AP was prepared as a complex with beta cyclodextrin (βCD) and hydroxy propyl beta cyclodextrin (HPβCD) in weight ratios 1:1, 1:2, and 1:3 by kneading, solvent evaporation and spray drying methods and characterized by Fourier transfer infra-red (FTIR), differential scanning calorimetry (DSC), and percent drug content in each of the prepared complex. Using the computer simulation, the interactions of AP with βCD and HPβCD were investigated. Key Results: The phase solubility study showed that the solubility of AP was greatly enhanced from 54×10-3 mmol /L to 66 mmol/L using HPβCD with acceptable stability constant. Computer docking supports the formation of a stable 1:1 complex between AP and CD’s. The dissolution test results showed that the complex gave a significantly higher percentage of drug release (95%) over one hour compared to the free AP (60%) (p<0.05). Conclusion: AP- HPβCD complex in the ratio of 1:2 (w/w) can significantly improve the solubility and in vitro dissolution rate of AP.