The ARCUS technology was initially developed in the labs of Dr. Robert Langer at MIT and Dr. David Edwards at Harvard. This initial development of large porous particles was described in a landmark 1997 Science article titled “Large Porous Particles for Pulmonary Drug Delivery”1. Shortly after this publication, a start-up company, Advanced Inhalation Research (AIR), was launched and began utilizing this approach to develop drug products for systemic drug delivery via the lung. Through various acquisitions and spinouts, the technology eventually became a commercial product, Inbrija®, in 2018 to treat OFF period tremor in Parkinson's patients.
A spray-dried particle engineering approach (ARCUS Technology) enabled dosing of 42mg of API in a single size 00 capsule while minimizing excipient content ( < 8 mg). These engineered powders are consistently taken up in a single breath due to their low density. Unlike traditional lactose-blended DPIs, high respirable fractions of >50% of the nominal dose are achieved over a broad range of inspiratory flow rates.
Clinical data indicated rapid onset at low and high dose loads and improved consistency in plasma concentrations compared to oral formulations which can vary with fed/fasted state. Inbrija® utilizes a device designed for a size 00 capsule which allows for high powder volume in a single capsule, where alternatively, approximately four size 3 capsules would be required for an equivalent dose.
Learning Objectives:
Understand how inhaled engineered particles can enable systemic therapy
Articulate how particle density/morphology effect pulmonary delivery.
Describe how 20 years of R&D led to a commercial product.
