Unveiling the Potential of Nanosuspension Formulation Strategy for Improved Oral Bioavailability of Gefitinib

Abstract

Gefitinib (GB), an oral tyrosine kinase inhibitor suffers major setbacks in clinical application due to limited aqueous solubility leading to poor oral bioavailability. Nanosuspension serves as a promising formulation strategy to overcome the above-mentioned drawbacks. Hence, the present study involves the development of gefitinib nanosuspension (GB-NS) using High-pressure homogenization (HPH) to increase its aqueous solubility and maximize oral bioavailability.

GB-NS was optimized by utilizing the quality-by-design strategy to optimize independent variables such as homogenization pressure, drug-to-stabilizer ratio, and number of cycles. Lecithin was found to stabilize the nanosuspension with optimal particle size, PDI, and zeta potential of 157 ± 18.77 nm, 0.296 ± 0.040, and -33.25 respectively. Intriguingly, a drug-to-stabilizer ratio significantly influenced (p < 0.005) particle size and PDI, establishing its crucial role in optimization.

The morphological characterization by SEM of GB-NS revealed a rod-shaped structure. Thereafter, the thermal and powder X-ray analysis depicted the crystalline nature of gefitinib in GB-NS. Additionally, GB-NS exhibited enhanced saturation solubility (~ 2.4- and ~ 3.4-fold) and dissolution rate (~ 2.5- and ~ 3.5-fold) compared to pure GB in 0.1 N HCl and PBS 6.8 respectively. GB-NS remained stable under both storage conditions ( 25°C and 4°C).

Finally, the pharmacokinetic study depicted a considerable increase in C_max (~ 2.84-fold) and AUC_(0-t) (~ 3.87-fold) of GB-NS when compared to free GB. Therefore, developed formulations showed a competent solution for enhancing the oral bioavailability of poor water-soluble drugs.

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Materials

Gefitinib was procured from Mac Chem India. HPMC, Lecithin, Pluronic® F-127, PVP-K30, Sodium lauryl sulfate (SLS), and Tween 80, fetal bovine serum (FBS) and 3-[4,5-dimethylthiazol-2-yl]−2,5 diphenyl tetrazolium bromide (MTT) reagent was procured from Sigma Aldrich, St. Louis, USA. Solvents like acetonitrile (ACN, HPLC grade), methanol (HPLC grade), and glacial acetic acid (GAA) were purchased from Fischer Scientific, USA. Analytical-grade chemicals and ultra-pure deionized water were used for the experiments.

Sayyad, P., Jha, S., Sharma, R. et al. Unveiling the Potential of Nanosuspension Formulation Strategy for Improved Oral Bioavailability of Gefitinib. AAPS PharmSciTech 26, 59 (2025). https://doi.org/10.1208/s12249-025-03040-8

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