High-dose dry powder inhaler for dual pulmonary and oral indomethacin delivery

Background

Dry powder inhalers (DPIs) offer a non-invasive and rapid route for drug delivery, particularly for medications requiring swift systemic action. This is especially relevant for poorly soluble drugs such as indomethacin, where oral administration is often limited by gastrointestinal degradation and adverse side effects. For indications like acute headache relief, achieving rapid and sustained plasma levels is critical. While DPIs are valued for their portability and stability, current formulations fall short when tasked with delivering high therapeutic doses efficiently and reproducibly.

Standard DPI approaches rely on lactose carriers to enhance powder dispersibility, but they typically yield low fine particle fractions and inconsistent pulmonary delivery. Increasing the powder load often diminishes aerosolization performance, reducing respirable dose. Additionally, conventional carrier-free blends suffer from high cohesion and poor flowability, limiting the achievable dose and contributing to suboptimal plasma drug concentrations. These limitations restrict the clinical potential of DPI-based formulations for rapid and sustained delivery of anti-inflammatory therapies.

Technology overview

This dry powder inhaler technology employs a novel drug-as-carrier formulation, blending coarse and micronized indomethacin particles in a 1:1 (w/w) ratio to achieve high respirable doses while maintaining excellent aerosol performance. Unlike lactose-based systems, this approach eliminates excipients by using indomethacin itself as both the active ingredient and flow enhancer. The optimized blend supports powder fill weights of 50-65 mg and delivers over 3 mg of respirable dose per inhalation, substantially higher than conventional DPIs. Performance evaluations using a medium-resistance inhaler and next-generation impactor demonstrated superior fine particle fractions compared to traditional lactose-carrier and carrier-free alternatives. The coarse fraction deposits in the oropharyngeal region and dissolves for secondary oral absorption, complementing the immediate pulmonary delivery. This dual-deposition mechanism enables rapid onset action and sustained plasma exposure, improving pharmacokinetics and reducing the gastrointestinal side effects associated with oral NSAIDs. RODOS dispersion studies confirmed favorable interparticle interactions and consistent deagglomeration, enabling high-dose delivery without compromising uniformity or performance.