A novel platform for DP inhalation drugs

Pulmonary drug delivery offers several advantages for both local and systemic applications. For drugs to treat diseases that are inherent to the respiratory tract, drug delivery via inhalation results in local, direct targeting of the site of action and minimisation of systemic exposure and side-effects.

For systemic applications, the primary advantages of pulmonary drug delivery can include:

• High bioavailability and rapid onset of action
• Avoidance of first pass metabolism
• Elimination of injection with its associated complications and
• Convenience for patients

Current technologies for the inhaled delivery of dry powder (DP) have some fundamental limitations for broad use with existing and novel drug molecules. Traditional DP inhalation delivery utilises lactose blends to deliver respirable micronised drug particles with large lactose carrier particles.

These blends are typically composed of over 80–90% lactose with microgram quantities of drug, resulting in a low drug mass to volume of powder ratio that limits their use primarily to high potency drugs. These powders are also generally highly flow rate dependent with respect to their dispersibility, have poor delivery efficiency with typically less than 20% of drug reaching the lung, and have high patient-to-patient variability.

Second-generation DP delivery, based on particle engineering approaches rather than active devices, has included production of porous particles and coating of particles with hydrophobic force-modifying excipients, such as magnesium stearate. Porous particles allow for aerosolisable powders with good dispersibility over a wide range of inspiratory flow rates. However, the inherent low particle density results in a low drug mass to volume of powder inhaled. The reduction in amount of drug per unit volume can make porous particles unsuitable for large molecule drugs or drug combinations that often require higher effective drug mass loadings per dose.