Expanding the opportunities of inhalation therapy in drug delivery

Inhaled drug delivery forms the basis of many respiratory disease treatment regimes. Dr. Nveed Chaudhary, chief scientific and regulatory officer at Broughton, shares how developments in inhaled drug delivery technology could both improve the treatment of these diseases, and enable the delivery of a wider range of active substances  - from anaesthetics to generic drug delivery.

Key insights:

• Unlike a drug delivered via intravenous injection, inhaled drug delivery doesn't need to pass around the body before reaching its target and is therefore less likely to be metabolised.
• There is an increasing demand for aerosol and inhalation products to improve patient outcomes in the treatment of respiratory disease and other conditions.
• There are opportunities for developing generic drugs via inhalation, as well as corticosteroids and anaesthetics - with the intention of lowering dose and mitigating side effects.

For treatment of diseases of the lung, throat, and oesophagus, the most obvious advantage of inhalation therapy is target organ delivery. However, there are distinct advantages to delivering pharmaceuticals via inhalation therapy where target organ delivery is not the primary focus.

One such advantage is that delivering an active substance into the alveolar spaces of the lung results in rapid absorption into oxygenated blood. The substance can therefore reach its target organ quickly and relatively intact. This means that, unlike a drug delivered via intravenous injection, it does not need to pass around the body before reaching its target and is therefore less likely to be metabolised. As a result, inhalation therapy can achieve efficacy with a lower dose, potentially reducing the risk of side effects and adverse events.

Another benefit of inhalation therapy comes with the advent of smart inhalation devices, which can give clinicians data on patient compliance in a way that no other current therapy can.

Common applications of inhalation therapy

Inhalation therapy is widely used in the treatment of a number of acute and chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis.

The appropriate delivery of the active substance depends on a number of factors including the patient, the drug delivery device, and the aerosol formulation. In particular, the particle size of aerosol droplets is an important determiner in where they are deposited. For high delivery to the bronchi, particles should be fine, whereas targeting the upper respiratory tract or oesophagus requires larger particles.

There is appetite for aerosol and inhalation product development to improve patient outcomes in the treatment of respiratory disease and other conditions. Due to the abbreviated pathways many global regulators offer, it is easier to adapt an inhalation device to deliver a generic drug, or refine an existing aerosol, than to develop an entirely new molecule for inhalation. There has therefore been significant innovation in inhaled drug delivery devices, but there is still room for innovation.

New therapeutic avenues

There are opportunities to expand the use of inhalation therapy to target diseases outside of respiratory illness. Perhaps the most commonly known existing example is inhaled anaesthetics. Another growing area for inhalation therapy outside of respiratory disease is nicotine replacement therapies, where innovation has seen huge advances in delivery devices. In addition, clinical trials have shown the ability to deliver insulin via inhalation, although this method of drug delivery did not take off within the market.

There is ongoing research into the delivery of generic drugs via inhalation. For example, sildenafil (Viagra), was designed as an anti-hypertensive. However, the high doses required for the drug to be efficacious when administering it systemically via tablet cause such notable side effects that the drug is instead prescribed to treat erectile dysfunction. The lower doses made possible with inhalation therapy could be the key to being able to use sildenafil as a hypertensive as initially planned.

Another example is corticosteroids. Inhaled beclomethasone is routinely prescribed as a mainstream treatment for asthma and COPD, with very little to no side effects. For patients suffering exacerbations, the most common course of action is to prescribe the closely related prednisolone as tablets, typically administered for around four weeks. However, the side effects can be severe and include risk of infection, increased appetite, higher blood pressure, and mood swings. In addition, at the end of treatment, therapy must be slowly phased down to avoid side effects or a phenomenon known as “rebounding”. This example clearly shows the potential of lower dose inhalation to reduce systemic adverse events.

Future advances will help enable drug delivery by inhalation to a wider range of patients, as well as deliver a broader range of therapeutic molecules. There is still work to be done in drug formulation and suspension, as the design of inhaled drugs is challenging, as well as in developing the delivery devices to suit the novel approach. Wherever possible, the development of the device and drug should be performed in parallel.