Dissolution enhancement of Gefitinib by solid dispersion and complexation with β-cyclodextrins: In vitro testing,...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Oncology

Background:

• Cancer is a leading global cause of mortality.
• Epidermal growth factor receptor (EGFR) is often overexpressed in metastatic non-small cell lung cancer (NSCLC).
• Gefitinib (GEF), an EGFR inhibitor, treats metastatic NSCLC but suffers from poor solubility and bioavailability.

Purpose of the Study:

• To enhance the dissolution and bioavailability of Gefitinib (GEF).
• To investigate the efficacy of solid dispersion (SD) and complexation techniques for improving GEF solubility.
• To evaluate the in-vitro cytotoxicity and tablet formulation of optimized GEF formulations.

Main Methods:

• GEF complexes were prepared with methyl-β-cyclodextrin (MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) in 1:1 and 1:2 molar ratios.
• GEF solid dispersions (SDs) were prepared using polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and poloxamer-188 (PXM) in various weight ratios (1:2, 1:4, 1:6 w/w).
• Dissolution studies, in-vitro cytotoxicity assays, and tablet formulation evaluations were performed.

Main Results:

• Dissolution studies showed a 1.22-2.17-fold enhancement in GEF dissolution after one hour compared to untreated GEF.
• Selected PVP-GEF (1:4 w/w) and MβCD-GEF (1:1M) formulations exhibited significantly lower IC50 values (4.33 ± 0.66 µM and 4.84 ± 0.38 µM, respectively) compared to free GEF (p < 0.05).
• Formulated tablets showed enhanced GEF release: PVP-GEF SD tablets released 35.1% ± 0.4 and GEF-MβCD tablets released 42.2% ± 0.7 after one hour, compared to 15% ± 0.5 for pure GEF tablets.

Conclusions:

• Solid dispersion and complexation effectively enhance Gefitinib dissolution and bioavailability.
• Optimized GEF formulations demonstrate improved in-vitro cytotoxicity.
• These findings offer a promising strategy to improve GEF's therapeutic potential in NSCLC treatment.