SESSION TITLE: Emerging Therapies in COPD
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Tuesday, October 27, 2015 at 02:45 PM - 04:15 PM
PURPOSE: Aside from convenience and improvements in patient compliance, inhaled combination therapies provide improved therapeutic effects due to synergistic drug action on the cellular level (1). This synergy may not be fully realized by traditional blended combinations since separate particles may not provide consistent delivery to each region of the lung. Researchers have presented a solution to this problem by engineering multiple drugs into single inhalable particles. In this study, we have applied Thin Film Freezing (TFF) to produce Brittle Matrix Powders (BMP) containing three actives in single particles that are suitable for inhalation
METHODS: An aerosolizable BMP was produced by TFF containing a triple combination of formoterol fumarate (FF), tiotropium bromide (TB), and budesonide (B) in a 1:2:35.5 FF:TB:B mass ratio. Mannitol was included as a stabilizing excipient so that the total drug loading was 50%. Aerosols were delivered from a HandiHaler® and characterized by Next Generation Pharmaceutical Impaction (NGI) to determine emitted dose (ED) and fine particle fraction (FPF). For comparison, the same drug/excipient combination was micronized, blended and characterized.
RESULTS: Cascade impactor testing of BMP triple combination of FF, TB and B demonstrated improved ED (97%) and FPF (53%) as well as a nearly identical regional distribution among impactor stages. In comparison, micronized blends produced an ED of 83% and FPF of 26% with an inconsistent regional distribution. BMP formulation ensured that individual APIs were deposited in a homogenous manner throughout the impactor.
CONCLUSIONS: BMP formulation of combination products for inhalation is a feasible approach to promote improved dose uniformity and co-deposition compared to traditional micronized blends.
CLINICAL IMPLICATIONS: This BMP triple combination could improve therapy in patients where β2-agonists receptors are downregulated and long-acting muscarinic antagonist (LAMA) sensitivity is increased. Additionally, it has been theorized that long-acting β2-agonists (LABA) have the ability to prime glucocorticosteroid receptors. Unlike micronized combinations inhalers, co-deposition is possible using BMP, increasing the potential for synergistic drug action (2). Ultimately, this technology could result in simplified development of multi-drug inhaled products, increased patient compliance and improved therapeutic outcomes. 1. J Allergy Clin Immunol 2003, 112:29-36. 2. Pharm Res 2013, 30:813-825 . .
DISCLOSURE: The following authors have nothing to disclose: Alan Watts, Jay Peters, Simone Carvalho, Robert Williams
This is a bench study of a single particle containing a LAMA,LABA, and ICS delivered via a commercially available device and demonstrates that all three components can be delivered to the same area of the lung. Testing was done in a new generation impactor under standard FDA conditions. The technology is of think film freezing into a brittle matrix is owned by the University of Texas Board of Regents and currently being tested in respiratory cells in culture and small animal experiments.