Development of Erlotinib Nanoliposome-Loaded Dry Powder Inhaler for Enhanced Pulmonary Delivery
Mayur R. Nikam, D. Sonawane, A. Pawar
Abstract
Objectives: To develop erlotinib nanoliposome-loaded dry powder inhaler formulations for targeted pulmonary delivery in non-small cell lung cancer, addressing the limitations of poor aqueous solubility, systemic toxicity, and suboptimal tumor localization associated with conventional erlotinib therapy. Methods: Six DPI formulations (IF1–IF6) were prepared by co-spray drying of pre-optimized erlotinib nanoliposomes with varying concentrations of lactose monohydrate, mannitol, and L-leucine as carrier excipients. Formulations were systematically evaluated for physicochemical properties, powder flow, aerodynamic performance using Andersen Cascade Impactor, in vitro drug release in simulated lung fluid, solid-state characterization, and accelerated stability under ICH Q1A(R2) conditions. The optimized batch was selected based on superior aerodynamic performance and overall physicochemical attributes. Results: Particle size D50 ranged from 4.82±0.18 μm (IF1) to 2.98±0.22 μm (IF6), with entrapment efficiency of 84.6–88.1% post spray drying. Formulation IF5 was identified as optimal, demonstrating MMAD of 3.18±0.21 μm, FPF of 56.4±1.9%, emitted dose of 88.2±1.4%, and cumulative drug release of 93.4±2.7% over 12 hours in simulated lung fluid. Drug release followed Hixson-Crowell kinetics (R²=0.9986) with anomalous non-Fickian diffusion confirmed by Korsmeyer-Peppas exponent n=0.7153. Accelerated stability studies confirmed no statistically significant changes in critical quality attributes over six months (p>0.05). Conclusion: The developed nanoliposomal DPI system offers a clinically significant advancement in site-specific pulmonary erlotinib delivery, with potential to improve therapeutic outcomes and reduce systemic adverse effects in NSCLC patients, warranting further in vivo pharmacokinetic and efficacy validation.